Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis.

PubMed

Mugwanya, Kenneth K; Donnell, Deborah; Celum, Connie; Thomas, Katherine K; Ndase, Patrick; Mugo, Nelly; Katabira, Elly; Ngure, Kenneth; Baeten, Jared M

2013-12-01

Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour. We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex-unprotected by a condom-during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour. We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011. Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk-taking sexual behaviour by heterosexual couples. The Bill & Melinda Gates Foundation and the US National Institute of Mental Health. Copyright © 2013 Elsevier Ltd. All rights reserved.

Risk factors for human rabies in China.

PubMed

Gong, Z; He, F; Chen, Z

2012-02-01

In China, we have witnessed an increasing incidence of rabies in recent years and the number of deaths ranked first among the 39 notifiable infectious diseases. We conducted a case-control study to identify risk factors for human rabies infection and disease to recommend prevention and treatment among people exposed to rabies. Exposure site, pre-exposure prophylaxis and post-exposure prophylaxis were significantly associated with rabies infection. Exposure site at upper limb and trunk or at lower limb were at lower risk as compared with head-exposed patients. The OR was 0.09(95% CI: 0.009-0.93) and 0.01(95% CI: 0.001-0.115) respectively. Pre-exposure prophylaxis (OR = 0.05, 95% CI: 0.03-0.11) and post-exposure prophylaxis (OR = 0.02, 95% CI: 0.01-0.40) were both protective factors as compared with no prophylaxis. For patients who had post-exposure prophylaxis, dose for the first injection and immunity procedure were significantly associated with rabies infection. © 2011 Blackwell Verlag GmbH.

Post-Exposure Prophylaxis

MedlinePlus

... gov Reason Number 87 to Get an HIV Test Veterans #DoingItMyWay – Testing for HIV June 27th is National HIV Testing Day Ryan White and HIV Testing Day 2018 Additional Resources AIDSInfo – Occupational Post-exposure Prophylaxis (PEP) Guidelines AIDSInfo – Nonoccupational Post-exposure ...

HIV risk and awareness and interest in pre-exposure and post-exposure prophylaxis among sheltered women in Miami.

PubMed

Doblecki-Lewis, Susanne; Lester, Larissa; Schwartz, Bryanna; Collins, Constance; Johnson, Rai; Kobetz, Erin

2016-09-01

Pre- and non-occupational post-exposure prophylaxis for the prevention of HIV infection are recommended for adults at substantial risk of HIV. Women experiencing homelessness have increased risk of HIV infection compared with stably-housed women. We conducted a survey of 74 sheltered women at Lotus House Women's Shelter (Lotus House) in Miami to assess risk behaviour as well as knowledge and perception of pre- and non-occupational post-exposure prophylaxis in this population. Of surveyed women, 58.1% engaged in vaginal and/or anal sex while sheltered, and of sexually-active women 55.4% reported inconsistent condom use. 83.8% of women reported no concern regarding HIV acquisition due to their behaviour. Few women surveyed (20.8%) had previously heard of pre- or non-occupational post-exposure prophylaxis. The majority (58.3%) of respondents indicated receptiveness to these prevention methods when introduced. Those indicating that they would consider pre- or non-occupational post-exposure prophylaxis were significantly younger than those indicating that they would not consider these prevention strategies (p = 0.004). Education and referral for pre- and non-occupational post-exposure prophylaxis should be considered for sheltered women at risk of HIV infection. Additional research to optimise implementation of biomedical prevention strategies in this population is needed. © The Author(s) 2015.

Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

PubMed

Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

2012-05-09

Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p < 0.0001). Mean virus diversity was also lower in PrEP failures after 17 weeks (0.13% vs. 0.53% in controls, p < 0.0001). Our results in a macaque model of acute HIV infection suggest that infection during PrEP limits early virus evolution likely because of a direct antiviral effect of PrEP and/or reduced target cell availability. Reduced virus diversification during early infection might enhance immune control by slowing the selection of escape mutants.

Postpartum weight change among HIV-infected mothers by antiretroviral prophylaxis and infant feeding modality in a research setting.

PubMed

Cames, Cecile; Cournil, Amandine; de Vincenzi, Isabelle; Gaillard, Philippe; Meda, Nicolas; Luchters, Stanley; Nduati, Ruth; Naidu, Kevindra; Newell, Marie-Louise; Read, Jennifer S; Bork, Kirsten

2014-01-02

To assess the relationship between infant feeding, triple-antiretroviral prophylaxis and weight from 2 weeks (baseline) to 6 months postpartum among HIV-infected mothers in a mother-to-child transmission (MTCT) of HIV-prevention trial in five sub-Saharan African sites. HIV-infected pregnant women with CD4 cell counts of 200-500 cells/μl were counselled to choose breastfeeding to 6 months or replacement feeding from delivery. They were randomized to receive perinatal zidovudine and single-dose nevirapine or triple-antiretroviral MTCT prophylaxis until breastfeeding cessation. Mixed-effect linear models were used to compare maternal weight trajectories over time by infant feeding mode. Antiretroviral prophylaxis and BMI at baseline were examined as potential effect modifiers. Among 797 mothers, 620 (78%) initiated breastfeeding. Wasting (BMI <18.5) was rare at baseline (2%), whereas overweight/obesity (BMI ≥ 25) was common (40%). In the model including all women, breastfeeding was not associated with weight loss up to 6 months, irrespective of baseline BMI and antiretroviral prophylaxis. Triple-antiretroviral prophylaxis was associated with weight gain among replacement-feeding mothers with baseline BMI at least 25 (+0.54 kg/month; P < 0.0001). In the model including breastfeeding mothers only, triple-antiretroviral prophylaxis was associated with weight gain among mothers with baseline BMI at least 25 who ceased breastfeeding before 3 months postpartum (+0.33 kg/month; P = 0.03). The results suggest that breastfeeding up to 6 months postpartum is not detrimental for postpartum weight among well nourished HIV-infected mothers at intermediate-disease stage. In the absence of breastfeeding or after weaning, triple-antiretroviral prophylaxis is associated with weight gain among women with high BMI, even after cessation of prophylaxis.

Practices and impacts post-exposure to blood and body fluid in operating room nurses: A cross-sectional study.

PubMed

Kasatpibal, Nongyao; Whitney, JoAnne D; Katechanok, Sadubporn; Ngamsakulrat, Sukanya; Malairungsakul, Benjawan; Sirikulsathean, Pinyo; Nuntawinit, Chutatip; Muangnart, Thanisara

2016-05-01

Improper or inadequate actions taken after blood and body fluid exposures place individuals at risk for infection with bloodborne pathogens. This has potential, significant impact for health and well-being. To evaluate the practices and the personal impact experienced following blood and body fluid exposures among operating room nurses. A cross-sectional, multi-center study. Government and private hospitals from all parts of Thailand. Operating room nurses from 247 hospitals. A questionnaire eliciting responses on characteristics, post-exposure practices, and impacts was sent to 2500 operating room nurses. Usable questionnaires were returned by 2031 operating room nurses (81.2%). Of these 1270 had experience with blood and body fluid exposures (62.5%). Most operating room nurses did not report blood and body fluid exposures (60.9%). The major reasons of underreporting were low risk source (40.2%) and belief that they were not important to report (16.3%). Improper post-exposure practices were identified, 9.8% did not clean exposure area immediately, 18.0% squeezed out the wound, and 71.1% used antiseptic solution for cleansing a puncture wound. Post-exposure, 58.5% of them sought counseling, 16.3% took antiretroviral prophylaxis, 23.8% had serologic testing for hepatitis B and 43.1% for hepatitis C. The main personal impacts were anxiety (57.7%), stress (24.2%), and insomnia (10.2%). High underreporting, inappropriate post-exposure practices and impacts of exposure were identified from this study. Comprehensive education and effective training of post-exposure management may be keys to resolving these important problems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of early treatment programs on HIV epidemics: An immunity-based mathematical model.

PubMed

Rahman, S M Ashrafur; Vaidya, Naveen K; Zou, Xingfu

2016-10-01

While studies on pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) have demonstrated substantial advantages in controlling HIV transmission, the overall benefits of the programs with early initiation of antiretroviral therapy (ART) have not been fully understood and are still on debate. Here, we develop an immunity-based (CD4+ T cell count based) mathematical model to study the impacts of early treatment programs on HIV epidemics and the overall community-level immunity. The model is parametrized using the HIV prevalence data from South Africa and fully analyzed for stability of equilibria and infection persistence criteria. Using our model, we evaluate the effects of early treatment on the new infection transmission, disease death, basic reproduction number, HIV prevalence, and the community-level immunity. Our model predicts that the programs with early treatments significantly reduce the new infection transmission and increase the community-level immunity, but the treatments alone may not be enough to eliminate HIV epidemics. These findings, including the community-level immunity, might provide helpful information for proper implementation of HIV treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

An overview of antiretroviral pre-exposure prophylaxis of HIV infection.

PubMed

McGowan, Ian

2014-06-01

Despite improvements in access to antiretroviral therapy and the use of simplified dosing regimens, HIV infection is still an important global public health problem. As a consequence, significant research efforts have been focused on the development of strategies to prevent the acquisition of HIV infection. These efforts have begun to produce results. The HPTN-052 study demonstrated the effectiveness of treating infected individuals as a means to prevent onward transmission of HIV infection. In addition, Phase 2B/3 studies have shown that the use of oral and topical antiretroviral pre-exposure prophylaxis (PrEP) can significantly reduce the acquisition of HIV infection in serodiscordant couples, young women in sub-Saharan Africa, men who have sex with men, and intravenous drug users. Despite these successes, challenges remain. Adherence to daily PrEP is variable, and some large studies have failed to demonstrate the effectiveness of PrEP in reducing HIV acquisition. Novel PrEP technologies, including sustained delivery intravaginal rings and long-acting injectable products, are being developed to try and circumvent adherence problems associated with daily PrEP regimens. The purpose of this article is to briefly summarize recent progress in the development of antiretroviral PrEP. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

How familiar are our doctors towards Rabies prophylaxis- A study from coastal south India.

PubMed

Holla, Ramesh; Darshan, Bhagawan; Guliani, Astha; Unnikrishnan, Bhaskaran; Thapar, Rekha; Mithra, Prasanna; Kumar, Nithin; Kulkarni, Vaman; Kumar, Avinash; Anwar, Salman

2017-10-01

Rabies, a 100% fatal disease claims more than 59,000 human lives every year globally. One human life is lost every 15 minutes due to this deadly preventable disease. Timely initiation of post exposure prophylaxis following an animal exposure can result in 100% preventability of this fatal disease. This facility based study was conducted among clinical fraternities of teaching hospitals. A semi structured questionnaire was used for collection of data. Institutional Ethics Committee approval was sought. The study investigators visited the workplace of the participants and distributed the questionnaire. SPSS Ver 16 (Chicago, IL, USA) was used to analyse the data. Most of the participants knew that veterinary groups and zoo-keepers should be given pre-exposure prophylaxis. Many participants knew about the Intra Muscular schedule of anti-rabies vaccine and its site of administration for pre exposure prophylaxis. It was observed that most participants had knowledge regarding correct intramuscular regimen of anti-rabies vaccine for post-exposure prophylaxis but less than half were able to differentiate between the intramuscular and intradermal regimens. Less than half of participants were aware of the fact that local administration of anti-rabies serum is useful. The knowledge regarding WHO categorisation of animal exposure and recommended post exposure prophylaxis according to type of exposure observed to be minimal among clinical fraternity.

The informal use of antiretroviral medications for HIV prevention by men who have sex with men in South Florida: initiation, use practices, medications and motivations.

PubMed

Buttram, Mance E

2018-01-23

Limited data suggest that some gay and other men who have sex with men are using antiretroviral medications informally, without a prescription, for HIV prevention. This qualitative study examined this phenomenon among gay and other men who have sex with men in South Florida. Participants initiated informal antiretroviral medication use as a means of protecting each other and because of the confidence in knowledge of antiretroviral medications shared by their friends and sex partners. The most commonly used medications included Truvada and Stribild. Motivations for use included condom avoidance, risk reduction, and fear of recent HIV exposure. Participants described positive and negative sentiments related to informal use, including concerns about informal antiretroviral medications offering sufficient protection against HIV, and limited knowledge about pre-exposure prophylaxis (PrEP). Because the antiretroviral medications used for PrEP have the potential to prevent HIV infection, future research must consider the informal antiretroviral medication use and related concerns, including adherence, diversion and viral resistance.

HIV-seroconversion following sexual abuse.

PubMed

Meel, B L

2005-10-01

Transkei is a poverty stricken former black homeland, now a part of the Eastern Cape Province. Unemployment and the incidental violence are very high. Women are mainly responsible for bringing up their children. Single parenting is also common in this community. Sexual abuse of children is selected to be under-reported. This reports the case of a 13-year-old girl who was raped twice within three months and brought to the Sinawe Centre of the Nelson Mandela Academic Hospital. Failure to adhere to post exposure prophylaxis (PEP) has undermined the implementation of antiretroviral roll out programme by the government. The history, physical examination and laboratory investigations of this case are given. Preventive steps are suggested.

Acceptability and preferences for safer conception HIV prevention strategies: a qualitative study.

PubMed

Schwartz, Sheree R; West, Nora; Phofa, Rebecca; Yende, Nompumelelo; Sanne, Ian; Bassett, Jean; Van Rie, Annelies

2016-10-01

Safer conception strategies to reduce the HIV transmission risk include antiretroviral therapy for HIV-positive partners, pre-exposure prophylaxis for HIV-negative partners, condomless sex limited to fertile periods, and home-based self-insemination. Resistance to taking treatment or cultural concerns may limit uptake of strategies and intervention success. Understanding the acceptability and preferences between different approaches is important to optimise service delivery. Between February and July 2013, 42 adults (21 HIV-positive and 21 HIV-negative) receiving primary care at Witkoppen Health and Welfare Centre in Johannesburg, South Africa, participated in focus group discussions or in-depth interviews. Themes were analysed using a grounded theory approach. Acceptability of antiretroviral-based strategies varied. Concerns over side effects, antiretroviral treatment duration and beliefs that treatment is only for the sick were common barriers; however, desperation for a child was noted as a facilitator for uptake. HIV-negative men and HIV-positive women had favourable attitudes towards self-insemination, though paternity and safety concerns were raised. Self-insemination was generally preferred over pre-exposure prophylaxis by HIV-negative men, and antiretroviral-based strategies were preferred by couples with HIV-negative female partners, despite concerns raised about condomless sex while virally suppressed. Knowledge about the fertile window was low. A strong counselling component will be required for effective uptake and adherence to safer conception services. © The Author(s) 2016.

The Promise of Antiretrovirals for HIV Prevention

PubMed Central

Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition. PMID:22351302

Lay Social Resources for Support of Adherence to Antiretroviral Prophylaxis for HIV Prevention Among Serodiscordant Couples in sub-Saharan Africa: A Qualitative Study.

PubMed

Ware, Norma C; Pisarski, Emily E; Haberer, Jessica E; Wyatt, Monique A; Tumwesigye, Elioda; Baeten, Jared M; Celum, Connie L; Bangsberg, David R

2015-05-01

Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP.

Antiretroviral-based HIV-1 Prevention: Antiretroviral Treatment and Pre-Exposure Prophylaxis

PubMed Central

Celum, Connie; Baeten, Jared

2012-01-01

Antiretroviral-based HIV-1 prevention strategies – including antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and oral and topical pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition – are the most promising new approaches for decreasing HIV-1 spread. Observational studies among HIV-1 serodiscordant couples have associated ART initiation with a reduction in HIV-1 transmission risk of 80–92%, and a recent randomized trial demonstrated that earlier initiation of ART (i.e., at CD4 counts between 350 and 550 cells/mm3), in the context of virologic monitoring and adherence support, resulted in a 96% reduction in HIV-1 transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV-1 prevention as peri-coitally administered or daily-administered 1% tenofovir gel and daily oral tenofovir and combination emtricitabine/tenofovir. Completed studies have demonstrated HIV-1 protection efficacies ranging from 39% to 75%. However, two trials in African women have shown no HIV-1 protection with PrEP; the reasons for lack of efficacy in those trials are being investigated. Adherence is likely key to efficacy of antiretrovirals for HIV-1 prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV-1 prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV-1 infected persons at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1 and highest-risk HIV-1 negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness. PMID:23221365

Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?

PubMed Central

Brown, Alison E; Mohammed, Hamish; Ogaz, Dana; Kirwan, Peter D; Yung, Mandy; Nash, Sophie G; Furegato, Martina; Hughes, Gwenda; Connor, Nicky; Delpech, Valerie C; Gill, O Noel

2017-01-01

Since October 2015 up to September 2016, HIV diagnoses fell by 32% compared with October 2014–September 2015 among men who have sex with men (MSM) attending selected London sexual health clinics. This coincided with high HIV testing volumes and rapid initiation of treatment on diagnosis. The fall was most apparent in new HIV testers. Intensified testing of high-risk populations, combined with immediately received anti-retroviral therapy and a pre-exposure prophylaxis (PrEP) programme, may make elimination of HIV achievable. PMID:28662762

Neurologic illness following post-exposure prophylaxis with purifiled chick embryo cell antirabies vaccine.

PubMed

Chakravarty, A

2001-09-01

Clinical details of a neurologic illness simultating Guillain Barre syndrome developing in a patient after post-exposure prophylaxis with purified chick embryo cell (PCEC) anti-rabies vaccine is reported. Neurologic complication following PCEC vaccination has not been reported earlier.

The structure and outcomes of a HIV postexposure prophylaxis program in a high HIV prevalence setup in western Kenya.

PubMed

Siika, Abraham M; Nyandiko, Winston M; Mwangi, Ann; Waxman, Michael; Sidle, John E; Kimaiyo, Sylvester N; Wools-Kaloustian, Kara

2009-05-01

In 2001, HIV postexposure prophylaxis (PEP) was initiated in western Kenya. Design, implementation, and evolution of the PEP program are described. Patient data were analyzed for reasons, time to initiation, and PEP outcome. Occupational PEP was initiated first followed by nonoccupational PEP (nPEP). Antiretroviral regimens were based upon national PEP guidelines, affordability and availability, and prevailing HIV prevalence. Emerging side effects data and cost improvements influenced regimen changes. Between November 2001 and December 2006, 446 patients sought PEP. Occupational exposure: 91 patients: 51 males; 72 accepted HIV testing; 48 of 52 source patients were HIV infected; median exposure-PEP time 3 hours (range: 0.3-96 hours). Of 72 HIV-negative patients receiving PEP, 3 discontinued, 69 completed, and 23 performed post-PEP HIV RNA polymerase chain reaction (all negative). Eleven follow-up HIV enzyme-linked immunosorbent assay tests have all turned negative. Nonoccupational exposure: 355 patients; 285 females; 90 children; 300 accepted HIV testing; median exposure-nPEP time 19 hours (range: 1-672 hours). Of 296 HIV-negative patients on nPEP, 1 died, 15 discontinued, 104 are on record having completed PEP, and 129 returned for 6-week HIV RNA polymerase chain reaction (1 patient tested positive). Eighty-seven follow-up HIV enzyme-linked immunosorbent assay tests have all turned negative. It is feasible to provide PEP and nPEP in resource-constrained settings.

Antiretroviral Prophylaxis for HIV-1 Prevention among Heterosexual Men and Women

PubMed Central

Baeten, Jared M.; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R.; Campbell, James D.; Wangisi, Jonathan; Tappero, Jordan W.; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H.; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kakia, Aloysious; Odoyo, Josephine; Mucunguzi, Akasiima; Nakku-Joloba, Edith; Twesigye, Rogers; Ngure, Kenneth; Apaka, Cosmas; Tamooh, Harrison; Gabona, Fridah; Mujugira, Andrew; Panteleeff, Dana; Thomas, Katherine K.; Kidoguchi, Lara; Krows, Meighan; Revall, Jennifer; Morrison, Susan; Haugen, Harald; Emmanuel-Ogier, Mira; Ondrejcek, Lisa; Coombs, Robert W.; Frenkel, Lisa; Hendrix, Craig; Bumpus, Namandjé N.; Bangsberg, David; Haberer, Jessica E.; Stevens, Wendy S.; Lingappa, Jairam R.; Celum, Connie

2013-01-01

Introduction Antiretroviral pre-exposure prophylaxis (PrEP) reduces the incidence of acquisition of human immunodeficiency virus type 1 (HIV-1) in men who have sex with men and is a promising approach for preventing HIV-1 in heterosexual populations. Methods We conducted a randomized, three-arm trial of oral antiretroviral PrEP among heterosexual couples from Kenya and Uganda in which one member was HIV-1 seronegative and the other HIV-1 seropositive. Seronegative partners were randomly assigned to once-daily tenofovir (TDF), combination emtricitabine/tenofovir (FTC/TDF), or matching placebo and followed monthly for up to 36 months. At enrollment, HIV-1 seropositive partners were not eligible for antiretroviral therapy under national guidelines. All couples received standard HIV-1 treatment and prevention services, including individual and couples risk-reduction counseling and condoms. Results 4758 couples were enrolled; for 62%, the HIV-1 seronegative partner was male. For HIV-1 seropositive participants, the median CD4 count was 495 cells/μL (interquartile range 375–662). Of 82 post-randomization HIV-1 infections, 17 were among those assigned TDF (incidence 0.65 per 100 person-years), 13 among those assigned FTC/TDF (incidence 0.50 per 100 person-years), and 52 among those assigned placebo (incidence 1.99 per 100 person-years), indicating a 67% relative reduction in HIV-1 incidence for TDF (95% CI 44 to 81, p<0.001) and 75% for FTC/TDF (95% CI 55 to 87, p<0.001). HIV-1 protective effects of FTC/TDF and TDF were not significantly different (p=0.23), and both study medications significantly reduced HIV-1 incidence in both men and women. The rate of serious medical events was similar across the study arms. Conclusions Oral TDF and FTC/TDF provided substantial protection against HIV-1 acquisition in heterosexual men and women, with comparable efficacy of TDF and FTC/TDF. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number NCT00557245) PMID:22784037

Fatal case of human rabies imported to Italy from India highlights the importance of adequate post-exposure prophylaxis, October 2011.

PubMed

De Benedictis, P; Perboni, G; Gentili, C; Gaetti, L; Zaffanella, F; Mutinelli, F; Capua, I; Cattoli, G

2012-05-10

In October 2011, an Indian man resident in Italy was admitted to a hospital in Mantua, Italy with symptoms of acute encephalitis. Due to a recent history of bite by a suspected rabid dog in India, where he had received incomplete post-exposure treatment, rabies was suspected. The patient died after 22 days of intensive care treatment and rabies was confirmed post mortem. This report stresses the need of appropriate post-exposure prophylaxis in rabies-endemic countries.

HIV among Women

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

HIV Among Asians

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?

PubMed

Brown, Alison E; Mohammed, Hamish; Ogaz, Dana; Kirwan, Peter D; Yung, Mandy; Nash, Sophie G; Furegato, Martina; Hughes, Gwenda; Connor, Nicky; Delpech, Valerie C; Gill, O Noel

2017-06-22

Since October 2015 up to September 2016, HIV diagnoses fell by 32% compared with October 2014-September 2015 among men who have sex with men (MSM) attending selected London sexual health clinics. This coincided with high HIV testing volumes and rapid initiation of treatment on diagnosis. The fall was most apparent in new HIV testers. Intensified testing of high-risk populations, combined with immediately received anti-retroviral therapy and a pre-exposure prophylaxis (PrEP) programme, may make elimination of HIV achievable. This article is copyright of The Authors, 2017.

The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection.

PubMed

Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna

2017-05-01

People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

HIV among Transgender People

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

HIV Testing

MedlinePlus

... NAT means. Taking pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) may also reduce the accuracy of NAT if you have HIV. An antigen/antibody test looks for both HIV antibodies and antigens. Antibodies ...

HIV Risk and Prevention

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

HIV/AIDS among African Americans

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

HIV Among People Aged 50 and Over

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

HIV among Pregnant Women, Infants, and Children

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

HIV among Gay and Bisexual Men

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

Audit of rabies post-exposure prophylaxis in England and Wales in 1990 and 2000.

PubMed

Hossain, J; Crowcroft, N S; Lea, G; Brown, D; Mortimer, P P

2004-06-01

The objectives were to compare rabies post-exposure prophylaxis issued by the Public Health Laboratory Service (PHLS) in 1990 and in 2000, to evaluate their appropriateness, and to make recommendations for future issue of rabies post-exposure prophylaxis in England and Wales. The method was to review all rabies vaccine and immunoglobulin issues by PHLS in 1990 and 2000 with evaluation against Department of Health recommendations. The PHLS issued prophylaxis to 656 people in 1990 and 295 people in 2000. The fall is attributable to control measures in Western Europe leading to a lower risk of exposure in countries in the region. Vaccine was still issued for exposures in countries with a category of 'no risk' (15 individuals) including rabies immunoglobulin in six cases. Immunoglobulin was frequently not issued for exposures in high-risk countries but the reasons were not always evident from the information provided; in many cases treatment had probably been started abroad. Delay before contacting the PHLS fell between 1990 and 2000 (p = 0.003). Dogs continue to be the most common animal exposure reported, and their rabies status is generally unknown. The most frequent site of bite was the leg. Prophylaxis was issued for exposure to some animals which have never been known to transmit rabies. Successful control measures in Europe have reduced the need for rabies prophylaxis in UK residents who travel abroad. More detailed information should be collected in future on aspects such as pre-exposure vaccination and treatment started abroad to facilitate future audit of appropriateness of treatment. A repeat audit should be carried out to evaluate the impact of a death from European Bat Lyssavirus 2 infection in a UK bat handler in November 2002.

HIV among African American Gay and Bisexual Men

MedlinePlus

... Determination of Need Requests Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment as Prevention Condoms HIV in the Workplace HIV Testing Laboratory Tests Home Tests Testing in Nonclinical Settings CLIA Certificate ...

Strategies to prevent HIV transmission to serodiscordant couples.

PubMed

Hallal, Ronaldo Campos; Raxach, Juan Carlos; Barcellos, Nêmora Tregnago; Maksud, Ivia

2015-09-01

The use antiretroviral reduces the sexual transmission of HIV, expanding interventions for serodiscordant couples. This article aims to review the use of antiretroviral and other prevention interventions among serodiscordant couples and to analyze its use in Brazil. A retrospective review was performed through the MEDLINE database and bases included in the Biblioteca Virtual em Saúde. The articles recovered exhibit four main strategies: (1) condom; (2) reduction of risks in sexual practices; (3) use of antiretrovirals, particularly early initiation of antiretroviral therapy (TASP) and pre-exposure prophylaxis (PrEP); (4) risk reduction in reproduction. TASP is highly effective in reducing sexual transmission, PrEP was tested in serodiscordant couples and both reduce the sexual transmission risk in different sexual practices, enabling individualized prevention strategies. When used in combination, antiretrovirals and sexual practices with condoms offer greater efficacy than any single strategy. The combined use of new and old strategies allows us to build a prevention policy for all.

Configuring the users of new HIV-prevention technologies: the case of HIV pre-exposure prophylaxis.

PubMed

Holt, Martin

2015-01-01

HIV pre-exposure prophylaxis (PrEP) is a prevention technology that involves prescribing antiretroviral drugs to HIV-negative people to protect them from infection. This paper considers how the development of the technology has necessitated the parallel configuration of its users, and how this process has affected the perception and uptake of the technology. In designing a technology, potential users are typically defined, enabled and constrained, partly to create a target population (or market) for the technology, but also to reassure people that it can be used safely and effectively. This process may or may not be helpful for the uptake and use of the technology. Published research on PrEP indicates that while the technology was under trial, the primary focus was on the 'at-risk' subject in need of PrEP, with little or no consideration of the other qualities necessary for successful use. Post-trial accounts of PrEP have begun to outline desirable qualities of successful PrEP use, such as caution, compliance and being organised. It appears that the PrEP user was only partially configured during the technology's development, and the initial focus on risk has done little to counter fears of the technology, which may partially account for its slow uptake.

Maternal CD4+ cell count decline after interruption of antiretroviral prophylaxis for the prevention of mother-to-child transmission of HIV.

PubMed

Ekouevi, Didier; Abrams, Elaine J; Schlesinger, Malka; Myer, Landon; Phanuphak, Nittaya; Carter, Rosalind J

2012-01-01

We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program. Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm(3) at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm(3) or <200 cells/mm(3) at 24 months. Weibull regression was used for multivariable analysis. A total of 1,393 women with enrollment CD4+ ≥250 cells/mm(3) initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23-30), median CD4+ was 469 cells/mm(3) (IQR: 363-613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm(3) was 12% (95% CI: 10-14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm(3) was 28%; (95% CI: 25-32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm(3): 46% (CD4+400-499 cells/mm(3)) vs. 19% (CD4+ ≥500 cells/mm(3)). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm(3) within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5-3.2, p<0.0001). Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

Misunderstanding of Pre-Exposure Prophylaxis Use Among Men Who Have Sex with Men: Public Health and Policy Implications.

PubMed

Kurtz, Steven P; Buttram, Mance E

2016-12-01

Street markets in antiretroviral medications for HIV have been documented, but sources of demand are not well understood. We report unexpected findings from qualitative research suggesting that some demand is for informal pre-exposure prophylaxis (PrEP). Focus groups with young men who have sex with men (N = 31) yielded information on their understanding and use of PrEP. Of those who had heard of it, few understood PrEP to be a physician-prescribed regimen; most believed it to be a pill taken before and/or after sex and acquired on the street or through HIV-positive friends. Implications for PrEP rollout and public health policy are discussed.

Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.

PubMed

Longstreth, Janice; Skiadopoulos, Mario H; Hopkins, Robert J

2016-12-01

The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.

How can we get close to zero? The potential contribution of biomedical prevention and the investment framework towards an effective response to HIV.

PubMed

Stover, John; Hallett, Timothy B; Wu, Zunyou; Warren, Mitchell; Gopalappa, Chaitra; Pretorius, Carel; Ghys, Peter D; Montaner, Julio; Schwartländer, Bernhard

2014-01-01

In 2011 an Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services resulting in a reduction of new HIV infections by more than half. However, it also estimated a leveling in the number of new infections at about 1 million annually after 2015. We modeled how the response to AIDS can be further expanded by scaling up antiretroviral treatment (ART) within the framework provided by the 2013 WHO treatment guidelines. We further explored the potential contributions of new prevention technologies: 'Test and Treat', pre-exposure prophylaxis and an HIV vaccine. Immediate aggressive scale up of existing approaches including the 2013 WHO guidelines could reduce new infections by 80%. A 'Test and Treat' approach could further reduce new infections. This could be further enhanced by a future highly effective pre-exposure prophylaxis and an HIV vaccine, so that a combination of all four approaches could reduce new infections to as low as 80,000 per year by 2050 and annual AIDS deaths to 260,000. In a set of ambitious scenarios, we find that immediate implementation of the 2013 WHO antiretroviral therapy guidelines could reduce new HIV infections by 80%. Further reductions may be achieved by moving to a 'Test and Treat' approach, and eventually by adding a highly effective pre-exposure prophylaxis and an HIV vaccine, if they become available.

Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation.

PubMed

Ross, Ian; Mejia, Carlos; Melendez, Johanna; Chan, Philip A; Nunn, Amy C; Powderly, William; Goodenberger, Katherine; Liu, Jingxia; Mayer, Kenneth H; Patel, Rupa R

2017-01-01

HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.

Using a network-based approach and targeted maximum likelihood estimation to evaluate the effect of adding pre-exposure prophylaxis to an ongoing test-and-treat trial.

PubMed

Balzer, Laura; Staples, Patrick; Onnela, Jukka-Pekka; DeGruttola, Victor

2017-04-01

Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger impact of pre-exposure prophylaxis. Offering pre-exposure prophylaxis to serodiscordant couples resulted in the largest reductions in HIV incidence (2% reduction), and the ring-based strategy had little impact (0% reduction). The joint effect was larger than either individual effect with reductions in the 7-year incidence ranging from 4.5% to 8.8%. Targeted maximum likelihood estimation, data-adaptively adjusting for baseline covariates, substantially improved power over the unadjusted analysis, while maintaining nominal confidence interval coverage. Our simulation study suggests that nesting a pre-exposure prophylaxis study within an ongoing trial can lead to combined intervention effects greater than those of universal test-and-treat alone and can provide information about the efficacy of pre-exposure prophylaxis in the presence of high coverage of treatment for HIV+ persons.

Antiviral agents and HIV prevention: controversies, conflicts, and consensus

PubMed Central

Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.

2013-01-01

Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation. PMID:22507927

The role of drugs in HIV prevention

NASA Astrophysics Data System (ADS)

Kembaren, T.

2018-03-01

WHO reports 36.7 million people are living with Human Immunodeficiency Virus (HIV) worldwide by 2016 with about 1.8 million new infections each year. It will be a specific health problem for the world in both developed and developing countries so it is necessary strategies to reduce HIV transmission to the community. HIV transmission in people with risk factors is largely determined by the amount of virus in the blood of people who are the source of infection. Antiretroviral (ARV) therapy has long been used in HIV patients, which serves to suppress viral replication so that the patient’s immunity increases; opportunistic infections are resolved and prolong the lifespan and lower transmission rates. In the HIV Prevention Trials Network (HPTN) study 052 there was a 96% reduction in transmission in earlier antiretroviral. ARV is also used in the prevention of transmission in people exposed to HIV virus that is Postexposure Prophylaxis as well as in people at risk before exposure (Pre-exposure Prophylaxis). Three prevention strategies with the provision of ARV is expected to be guided as a means of prevention of transmission in addition to behavioral changes has long been declared since the beginning of the HIV epidemic.

Cancer Among Children With Perinatal Exposure to HIV and Antiretroviral Medications--New Jersey, 1995-2010.

PubMed

Ivy, Wade; Nesheim, Steve R; Paul, Sindy M; Ibrahim, Abdel R; Chan, Miranda; Niu, Xiaoling; Lampe, Margaret A

2015-09-01

Concerns remain regarding the cancer risk associated with perinatal antiretroviral (ARV) exposure among infants. No excessive cancer risk has been found in short-term studies. Children born to HIV-infected women (HIV-exposed) in New Jersey from 1995 to 2008 were identified through the Enhanced HIV/AIDS Reporting System and cross-referenced with data from the New Jersey State Cancer Registry to identify new cases of cancer among children who were perinatally exposed to ARV. Matching of individuals in the Enhanced HIV/AIDS Reporting System to the New Jersey State Cancer Registry was conducted based on name, birth date, Social Security number, residential address, and sex using AutoMatch. Age- and sex-standardized incidence ratio (SIR) and exact 95% confidence intervals (CIs) were calculated using New Jersey (1979-2005) and US (1999-2009) cancer rates. Among 3087 children (29,099 person-years; median follow-up: 9.8 years), 4 were diagnosed with cancer. Cancer incidence among HIV-exposed children who were not exposed to ARV prophylaxis (22.5 per 100,000 person-years) did not differ significantly from the incidence among children who were exposed to any perinatal ARV prophylaxis (14.3 per 100,000 person-years). Furthermore, the number of cases observed among individuals exposed to ARV did not differ significantly from cases expected based on state (SIR = 1.21; 95% CI: 0.25 to 3.54) and national (SIR = 1.27; 95% CI: 0.26 to 3.70) reference rates. Our findings are reassuring that current use of ARV for perinatal HIV prophylaxis does not increase cancer risk. We found no evidence to alter the current federal guidelines of 2014 that recommend ARV prophylaxis of HIV-exposed infants.

HIV Post-Exposure Prophylaxis for Child Rape Survivors in KwaZulu-Natal, South Africa: Who Qualifies and Who Complies?

ERIC Educational Resources Information Center

Collings, Steven J.; Bugwandeen, Shikaar R.; Wiles, Wendy A.

2008-01-01

Objective: Our objective was to audit the provision and utilization of HIV post-exposure prophylaxis (PEP) to child rape survivors in the Province of KwaZulu-Natal, South Africa. Methods: A prospective design was used to collect data from a convenience sample of 200 consecutive cases of child rape referred for medico-legal assessment to a state…

Dissimilarities in the Metabolism of Antiretroviral Drugs used in HIV Pre-exposure Prophylaxis in Colon and Vagina Tissues

PubMed Central

To, Elaine E.; Hendrix, Craig W.; Bumpus, Namandjé N.

2013-01-01

Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. PMID:23965226

Alcohol-antiretroviral interactive toxicity beliefs as a potential barrier to HIV pre-exposure prophylaxis among men who have sex with men.

PubMed

Kalichman, Seth C; Eaton, Lisa

2017-07-17

Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. HIV-negative sexually active men who have sex with men ( N  = 272) at a large Gay Pride event in Atlanta, GA, completed anonymous surveys of demographic characteristics, sexual behaviour, alcohol use and PrEP-related alcohol interactive toxicity beliefs. A total of 118 (43%) men surveyed had two or more male sex partners and condomless anal sex in the previous six months. Alcohol use was reported by over 90% of men and it was common for participants to believe that mixing alcohol and antiretrovirals is toxic; 75% endorsed at least one interactive toxicity belief. Among the 118 men who had engaged in condomless anal sex and had multiple sex partners, one in three stated that they were not interested in PrEP and men not interested in PrEP were significantly more likely to binge drink and hold interactive toxicity beliefs. These results mirror studies that find interactive toxicity beliefs are a potent predictor of intentional antiretroviral non-adherence among people living with HIV and suggest interactive toxicity beliefs may impede PrEP uptake and adherence. Messages to increase PrEP awareness and adherence may also take steps to counter erroneous beliefs about mixing alcohol with antiretrovirals in the context of PrEP.

What Primary Care Providers Need to Know about Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: Narrative Review

PubMed Central

Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

As HIV prevalence climbs globally, including more than 50,000 new infections per year in the United States, we need effective HIV prevention strategies. The use of antiretrovirals for pre-exposure prophylaxis (known as “PrEP”) among high-risk HIV-uninfected persons is emerging as one such strategy. Randomized controlled trials have demonstrated that once daily oral PrEP decreased HIV incidence among at-risk MSM and African heterosexuals, including HIV serodiscordant couples. An additional randomized control trial of a pericoital topical application of antiretroviral microbicide gel reduced HIV incidence among at-risk heterosexual South African women. Two other studies in African women did not demonstrate the efficacy of oral or topical PrEP, raising concerns about adherence patterns and efficacy in this population. The FDA Antiretroviral Advisory Panel reviewed these studies and additional data in May 2012 and recommended the approval of oral tenofovir-emtricitabine for PrEP in high-risk populations. Patients may seek PrEP from their primary care providers and those on PrEP require monitoring. Thus, primary care providers should become familiar with PrEP. This review outlines the current state of knowledge about PrEP as it pertains to primary care including identification of individuals likely to benefit from PrEP, counseling to maximize adherence and minimize potential increases in risky behavior, and monitoring for potential drug toxicities, HIV acquisition, and antiretroviral drug resistance. Issues related to cost and insurance coverage are also discussed. Recent data suggest that PrEP, in conjunction with other prevention strategies, holds promise in helping to curtail the HIV epidemic. PMID:22821365

Alcohol-antiretroviral interactive toxicity beliefs as a potential barrier to HIV pre-exposure prophylaxis among men who have sex with men

PubMed Central

Kalichman, Seth C; Eaton, Lisa

2017-01-01

Abstract Introduction: Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. Methods: HIV-negative sexually active men who have sex with men (N = 272) at a large Gay Pride event in Atlanta, GA, completed anonymous surveys of demographic characteristics, sexual behaviour, alcohol use and PrEP-related alcohol interactive toxicity beliefs. Results: A total of 118 (43%) men surveyed had two or more male sex partners and condomless anal sex in the previous six months. Alcohol use was reported by over 90% of men and it was common for participants to believe that mixing alcohol and antiretrovirals is toxic; 75% endorsed at least one interactive toxicity belief. Among the 118 men who had engaged in condomless anal sex and had multiple sex partners, one in three stated that they were not interested in PrEP and men not interested in PrEP were significantly more likely to binge drink and hold interactive toxicity beliefs. Conclusions: These results mirror studies that find interactive toxicity beliefs are a potent predictor of intentional antiretroviral non-adherence among people living with HIV and suggest interactive toxicity beliefs may impede PrEP uptake and adherence. Messages to increase PrEP awareness and adherence may also take steps to counter erroneous beliefs about mixing alcohol with antiretrovirals in the context of PrEP. PMID:28715159

Antiretroviral Therapy and Pre-exposure Prophylaxis: Combined Impact on HIV Transmission and Drug Resistance in South Africa

PubMed Central

Abbas, Ume L.; Glaubius, Robert; Mubayi, Anuj; Hood, Gregory; Mellors, John W.

2013-01-01

Background. The potential impact of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) with overlapping and nonoverlapping antiretrovirals (ARVs) on human immunodeficiency virus (HIV) transmission and drug resistance is unknown. Methods. A detailed mathematical model was used to simulate the epidemiological impact of ART alone, PrEP alone, and combined ART + PrEP in South Africa. Results. ART alone initiated at a CD4 lymphocyte cell count <200 cells/µL (80% coverage and 96% effectiveness) prevents 20% of HIV infections over 10 years but increases drug resistance prevalence to 6.6%. PrEP alone (30% coverage and 75% effectiveness) also prevents 21% of infections but with lower resistance prevalence of 0.5%. The ratio of cumulative infections prevented to prevalent drug-resistant cases after 10 years is 7-fold higher for PrEP than for ART. Combined ART + PrEP with overlapping ARVs prevents 35% of infections but increases resistance prevalence to 8.2%, whereas ART + PrEP with nonoverlapping ARVs prevents slightly more infections (37%) and reduces resistance prevalence to 7.2%. Conclusions. Combined ART + PrEP is likely to prevent more HIV infections than either strategy alone, but with higher prevalence of drug resistance. ART is predicted to contribute more to resistance than is PrEP. Optimizing both ART and PrEP effectiveness and delivery are the keys to preventing HIV transmission and drug resistance. PMID:23570850

Anti-retroviral Therapy Based HIV Prevention Among a Sample of Men Who Have Sex with Men in Cape Town, South Africa: Use of Post-exposure Prophylaxis and Knowledge on Pre-exposure Prophylaxis.

PubMed

Hugo, J M; Stall, R D; Rebe, K; Egan, J E; De Swardt, G; Struthers, H; McIntyre, J A

2016-12-01

Men who have Sex with Men (MSM) have been affected disproportionately by the global HIV pandemic. Rates of consistent condom-use are low and there is a need for further biomedical prevention interventions to prevent new HIV infections. Post exposure prophylaxis (PEP) can reduce the risk of HIV, but uptake among MSM is low. Pre-exposure prophylaxis (PrEP), an innovative anti-retroviral-based HIV prevention tool might be an appropriate intervention for MSM who have recently accessed PEP that involves HIV negative individuals taking daily tenofovir+emtricitabine for HIV prevention. 44 MSM, attending a primary health-care level MSM-focused sexual health clinic in Cape Town, South Africa, who had initiated PEP were enrolled in this study. Participants were followed up after 2, 4 and 12 weeks. Self-administered electronic surveys were completed at the initial, 4 and 12 week visit. Barriers and facilitators to accessing PEP and remaining adherent were examined, as was knowledge about PrEP. Thirty-two participants (80 %) were <40 years of age (range 20-65 years). 35 % of the participants reported their reason for requiring PEP as condomless receptive anal intercourse. A further 20 % required PEP following condomless penetrative anal intercourse; 27.5 % required PEP due to a broken condom during receptive anal sex and 2 participants during insertive anal sex. Three participants did not complete 28 days of PEP or were lost to follow up. Over half (58.5 %) of the participants reported being completely adherent to their regime; under a third (31.7 %) reported missing one PEP dose; and 9.8 % reported missing more than one dose. 36/40 (90 %) had heard of PrEP and 30/40 (75 %) indicated that they would use PrEP if it were accessible to them. That we enrolled 44 MSM who accessed PEP from a Department of Health affiliated clinic over 12 months, speaks to the low uptake by MSM of PEP services in South Africa. Adherence was high and demonstrates that adherence support is feasible from a state health clinic. Reported risk behaviors in some high-risk participants did not change over time, demonstrating the need for additional longer-term HIV preventions such as PrEP. PEP users could conceivably be transitioned from PEP to PrEP.

Comparison of tafenoquine (WR238605) and primaquine in the post-exposure (terminal) prophylaxis of vivax malaria in Australian Defence Force personnel.

PubMed

Nasveld, Peter; Kitchener, Scott; Edstein, Michael; Rieckmann, Karl

2002-01-01

On return from duty in North Solomons Province (including Bougainville Island), Papua New Guinea, 586 Australian Defence Force personnel received either primaquine (14-d) or tafenoquine (3-d) post-exposure malaria prophylaxis. Within 12 months, 6 of the 214 volunteers receiving primaquine and 7 of 378 receiving tafenoquine had developed vivax malaria. Overall, volunteers preferred the shorter course of tafenoquine.

Knowledge and attitudes of non-occupational HIV post-exposure prophylaxis amongst first- and second-year medical students at Stellenbosch University in South Africa

PubMed Central

Meintjes, Willem A.J.; Chola, Lumbwe

2014-01-01

Abstract Background Human immunodeficiency virus (HIV) infection is a worldwide problem, with 68% of infected people residing in sub-Saharan Africa. Antiretroviral therapy is used as post-exposure prophylaxis (PEP) to prevent infection in cases of occupational exposure, and use has recently been expanded to non-occupational exposure. Studies have demonstrated a lack of awareness of non-occupational PEP (NO-PEP) in the general population. Aim The aim of this study was to evaluate knowledge and attitudes towards availability of, access to and use of NO-PEP amongst first- and second-year medical students. Setting Participants were medical undergraduates of Stellenbosch University in the Western Cape of South Africa who were registered in 2013. Methods A descriptive cross-sectional study of 169 students was performed. Data were collected using self-administered questionnaires handed out in a classroom in August 2013. Self-reported knowledge and attitudes towards NO-PEP and barriers to access to and use of NO-PEP were analysed using frequency tables. Associations between self-reported and objective knowledge of NO-PEP were analysed by odds ratios. Results Over 90% of students had good knowledge on HIV transmission, and about 75% knew how it can be prevented. Twenty eight per cent (n = 47) of students reported knowledge of NO-PEP; 67% reported hearing about it from lecturers, whilst 1% reported hearing about it from their partner. Students who knew the correct procedure to take when a dose is forgotten were 2.4 times more likely to report knowledge of NO-PEP than those who did not know what to do when a dose is forgotten (p = 0.029). No other associations were statistically significant. Conclusion Students had positive attitudes towards the use of NO-PEP and also identified barriers to its use. Despite good knowledge of HIV prevention and transmission, knowledge on NO-PEP was poor. PMID:26245421

Post-exposure prophylaxis against rabies at two newly designated intradermal rabies vaccination clinics in Kerala, India.

PubMed

J, Teena M; Mathew, T; S, Anish T; M, Sujina C; Philip, R R

2012-01-01

The two-site intradermal rabies vaccination (IDRV) regimen was recently introduced in Kerala. We aimed to determine factors associated with exposure of category III severity among patients seeking prophylaxis against rabies at IDRV clinics. This hospital-based, cross-sectional study was done at two clinics in Thiruvananthapuram district, Kerala. Data were collected using a semi-structured questionnaire by direct interview and 320 patients were included. Bivariate analysis of quantitative variables was done using t-test and that of qualitative variables using chi-square test. The mean (standard deviation) age of patients was 32.4 (19.6) years. Among the 320 cases, 202 (63.1%) had category III exposure. Lower extremities were the most frequent site of exposure (146, 45.6%). The most frequent mode of exposure was being bitten by an animal (214, 66.9%), often a dog. Residence in rural areas, exposure to dogs and wounds on the extremities had a significant association with severity of exposure. Animal exposures were more among people from rural areas. About two-thirds of exposures which necessitated post-exposure prophylaxis were category III. Copyright 2012, NMJI.

Views of Medical Doctors Regarding the 2013 WHO Adult HIV Treatment Guidelines Indicate Variable Applicability for Routine Patient Monitoring, for Their Family Members and for Themselves, in South-Africa.

PubMed

Venter, Willem Daniel Francois; Fairlie, Lee; Feldman, Charles; Cleaton-Jones, Peter; Chersich, Matthew

2016-01-01

South African doctors (n = 211) experienced in antiretroviral therapy use were asked via an online questionnaire about the WHO 2013 adult antiretroviral integrated guidelines, as well as clinical and personal issues, in three hypothetical scenarios: directing the Minister of Health, advising a family member requiring therapy amidst unstable antiretroviral supplies, and where doctors themselves were HIV-positive. Doctors (54%) favoured the 500 cells/μl WHO initiation threshold if advising the Minister; a third recommended retaining the 350 cells/μl threshold used at the time of the survey. However, they favoured a higher initiation threshold for their family member. Doctors were 4.9 fold more likely to initiate modern treatment, irrespective of their CD4 cell count, for themselves than for public-sector patients (95%CI odds ratio = 3.33-7.33; P<0.001, although lower if limited to stavudine-containing regimens. Doctors were equally concerned about stavudine-induced lactic acidosis and lipoatrophy. The majority (84%) would use WHO-recommended first-line therapy, with concerns split between tenofovir-induced nephrotoxicity (55%), and efavirenz central nervous system effects (29%). A majority (61%), if HIV-positive, would pay for a pre-initiation resistance test, use influenza-prophylaxis (85%), but not INH-prophylaxis (61%), and treat their cholesterol and blood pressure concerns conventionally (63% and 60%). Over 60% wanted viral loads and creatinine measured six monthly. A third felt CD4 monitoring only necessary if clinically indicated or if virological failure occurred. They would use barrier prevention (83%), but not recommend pre-exposure prophylaxis, if their sexual partner was HIV-negative (68%). A minority would be completely open about their HIV status, but the majority would disclose to their sexual partners, close family and friends. Respondents were overwhelmingly in favour of continued antiretrovirals after breastfeeding. In conclusion, doctors largely supported adult WHO guidelines as public policy, although would initiate treatment at higher CD4 counts for their family and themselves. Resistance to INH-prophylaxis is unexpected and warrants investigation.

Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals.

PubMed

Okwundu, Charles I; Uthman, Olalekan A; Okoromah, Christy An

2012-07-11

More than 30 years into the global HIV/AIDS epidemic, infection rates remain alarmingly high, with over 2.7 million people becoming infected every year. There is a need for HIV prevention strategies that are more effective. Oral antiretroviral pre-exposure prophylaxis (PrEP) in high-risk individuals may be a reliable tool in preventing the transmission of HIV. To evaluate the effects of oral antiretroviral chemoprophylaxis in preventing HIV infection in HIV-uninfected high-risk individuals. We revised the search strategy from the previous version of the review and conducted an updated search of MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in April 2012. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing trials. Randomised controlled trials that evaluated the effects of any antiretroviral agent or combination of antiretroviral agents in preventing HIV infection in high-risk individuals Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors using a standardized data extraction form. Relative risk with a 95% confidence interval (CI) was used as the measure of effect. We identified 12 randomised controlled trials that meet the criteria for the review. Six were ongoing trials, four had been completed and two had been terminated early. Six studies with a total of 9849 participants provided data for this review. The trials evaluated the following: daily oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms: TDF, TDF-FTC and placebo arm. The studies were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, serodiscordant couples and other high risk men and women.Overall results from the four trials that compared TDF-FTC versus placebo showed a reduction in the risk of acquiring HIV infection (RR 0.51; 95% CI 0.30 to 0.86; 8918 participants). Similarly, the overall results of the studies that compared TDF only versus placebo showed a significant reduction in the risk of acquiring HIV infection (RR 0.38; 95% CI 0.23 to 0.63, 4027 participants). There were no significant differences in the risk of adverse events across all the studies that reported on adverse events. Also, adherence and sexual behaviours were similar in both the intervention and control groups. Finding from this review suggests that pre-exposure prophylaxis with TDF alone or TDF-FTC reduces the risk of acquiring HIV in high-risk individuals including people in serodiscordant relationships, men who have sex with men and other high risk men and women.

Differentiating Nonoccupational Postexposure Prophylaxis Seroconverters and Non-Seroconverters in a Community-Based Clinic in Los Angeles, California

PubMed Central

Weiss, Robert E.; Bolan, Robert K.; Kofron, Ryan M.; Flynn, Risa P.; Pieribone, David L.; Kulkarni, Sonali P.; Landovitz, Raphael J.

2017-01-01

Abstract Background. Nonoccupational postexposure prophylaxis (nPEP) is a 28-day regimen of antiretroviral medications taken within 72 hours of human immunodeficiency virus (HIV) exposure to prevent HIV acquisition. Although nPEP has been recommended since 1998, few studies have analyzed the characteristics that distinguish nPEP failures (seroconverters) and successes (non-seroconverters). Methods. This retrospective study analyzed all nPEP courses prompted by sexual exposure that were prescribed at the Los Angeles LGBT Center between March 2010 and July 2014. Fisher exact tests and logistic regressions were used to determine characteristics that distinguished nPEP seroconverters from non-seroconverters. Results. Of the nPEP courses administered, 1744 had a follow-up visit for HIV testing within 24 weeks of exposure and 17 individuals seroconverted. Seven reported a known re-exposure, 8 self-reported only condom-protected sex subsequent to the initial exposure, and 2 reported abstinence since the exposure. In multivariable analyses, seroconverters were more likely than non-seroconverters to report methamphetamine use, incomplete medication adherence, and nPEP initiation later in the 72-hour window. Conclusions. Nonoccupational postexposure prophylaxis is an important emergency tool for HIV prevention. Our findings corroborate that timing of the initial nPEP dose is an important predictor of seroconversion. Although the current study did not offer the initial nPEP dose at the beginning of the visit, use of this fast-track dosing schedule will ensure that the first dose is taken as early as possible postexposure and may lower the likelihood for seroconversion. Furthermore, we recommend systematic screening for substance use because these individuals may be well suited for pre-exposure prophylaxis given their sustained risk. PMID:28596981

Pre-exposure prophylaxis does not affect the fertility of HIV-1-uninfected men.

PubMed

Were, Edwin O; Heffron, Renee; Mugo, Nelly R; Celum, Connie; Mujugira, Andrew; Bukusi, Elizabeth A; Baeten, Jared M

2014-08-24

There is a paucity of data on the effect of antiretroviral medications on male fertility. Couples affected by HIV-1 often have fertility intentions, and antiretroviral medications, as both treatment of HIV-1-infected persons and pre-exposure prophylaxis (PrEP) for uninfected persons, are part of peri-conception risk reduction. Within a randomized, placebo-controlled trial of daily oral tenofovir disoproxil fumarate (TDF) and combination emtricitabine (FTC)/TDF PrEP for HIV-1 prevention conducted among heterosexual HIV-1-serodiscordant couples, we assessed the impact of TDF and FTC/TDF use on male fertility, measured as incident pregnancy in female partners of men assigned to PrEP vs. placebo. Of the 2962 HIV-1-uninfected men partners, 986 were randomized to TDF, 1013 to FTC/TDF, and 963 to placebo. The overall pregnancy incidence in their HIV-1-infected female partners was 12.9 per 100 person-years and did not differ significantly across the study arms (13.2 TDF, 12.4 FTC/TDF, 13.2 placebo). The frequency of live births, pregnancy losses, and gestational age at birth or loss was also statistically similar in the three randomization groups. TDF and FTC/TDF, when used as PrEP by HIV-1-uninfected men, did not adversely affect male fertility or pregnancy outcomes.

Recent advances in pre-exposure prophylaxis for HIV.

PubMed

Desai, Monica; Field, Nigel; Grant, Robert; McCormack, Sheena

2017-12-11

Although pre-exposure prophylaxis (PrEP)-the use of antiretroviral drugs by non-infected people to prevent the acquisition of HIV-is a promising preventive option, important public health questions remain. Daily oral emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) is highly efficacious in preventing the acquisition of HIV in people at risk as a result of a range of different types of sexual exposure. There is good evidence of efficacy in women and men, and when men who have sex with men use event based dosing. Studies have been conducted in several countries and epidemics. Because adherence to this treatment varies greatly there are questions about its public health benefit. Oral FTC-TDF is extremely safe, with minimal impact on kidney, bone, or pregnancy outcomes, and there is no evidence that its effectiveness has been reduced by risk compensation during open label and programmatic follow-up. It is too early to assess the impact of this treatment on the incidence of sexually transmitted infections (STIs) at a population level. Many challenges remain. Access to pre-exposure prophylaxis is limited and disparities exist, including those governed by race and sex. Different pricing and access models need to be explored to avoid further widening inequalities. The optimal combination prevention program needs to be defined, and this will depend on local epidemiology, service provision, and cost effectiveness. This review updates the evidence base for pre-exposure prophylaxis regarding its effectiveness, safety, and risk compensation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Neurodevelopment in children born to HIV-infected mothers by infection and treatment status.

PubMed

Le Doaré, Kirsty; Bland, Ruth; Newell, Marie-Louise

2012-11-01

We reviewed the impact of HIV, HIV exposure, and antiretroviral therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV-exposed-uninfected infants and children. A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990-March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if results were reported in children <16 years of age who were exposed to HIV and antiretrovirals in fetal/early life, and excluded if children did not acquire HIV from their mothers or were not exposed to antiretrovirals in fetal/early life. Infants who acquired HIV during fetal and early life tended to display poorer mean developmental scores than HIV-unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs below the population mean. Mean scores improved if the infant received treatment before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected children treated with highly active antiretroviral therapy demonstrated near normal global mean neurocognitive scores; subtle differences in language, memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech and language delay, although not universally. In comparison with resource-rich settings, HIV-infected and HIV-exposed-uninfected infants/children in resource-poor settings demonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from an early age and HIV-exposed-uninfected children particularly in resource-poor settings remain unclear.

Tenofovir Disoproxil Fumarate Fails to Prevent HIV Acquisition or the Establishment of a Viral Reservoir: Two Case Reports.

PubMed

Fox, Julie; Brady, Michael; Alexander, Hannah; Davies, Olubanke; Robinson, Nicola; Pace, Mathew; Else, Laura; Cason, John; Khoo, Saye; Back, David; Fidler, Sarah; Frater, John

2016-03-01

The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention. The World Health Organization recently recommended Truvada(®) (Gilead Sciences, Inc.) or tenofovir disoproxil fumarate (TDF) for high-risk individuals, with limited data for single-agent TDF PrEP in men who have sex with men (MSM). We report two cases of TDF PrEP failure in MSM who had received long-term TDF for hepatitis B infection and had therapeutic levels of drug immediately after HIV acquisition. Rapid antiretroviral intensification at diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.

Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre-exposure prophylaxis in colon and vagina tissues.

PubMed

To, Elaine E; Hendrix, Craig W; Bumpus, Namandjé N

2013-10-01

Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. Copyright © 2013 Elsevier Inc. All rights reserved.

Brief Report: Medication Sharing Is Rare Among African HIV-1 Serodiscordant Couples Enrolled in an Efficacy Trial of Oral Pre-exposure Prophylaxis (PrEP) for HIV-1 Prevention.

PubMed

Thomson, Kerry A; Haberer, Jessica E; Marzinke, Mark A; Mujugira, Andrew; Hendrix, Craig W; Celum, Connie; Ndase, Patrick; Ronald, Allan; Bangsberg, David R; Baeten, Jared M

2017-06-01

Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners. PrEP sharing was self-reported at <0.01% of visits, and 0%-1.6% of randomly selected and 0% of purposively selected specimens from HIV-1 infected participants had detectable tenofovir concentrations (median: 66.5 ng/mL, range: 1.3-292 ng/mL). PrEP sharing within HIV-1 serodiscordant couples was extremely rare.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

PubMed

Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

2016-07-12

New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

A lipid-based nutrient supplement mitigates weight loss among HIV-infected women in a factorial randomized trial to prevent mother-to-child transmission during exclusive breastfeeding.

PubMed

Kayira, Dumbani; Bentley, Margaret E; Wiener, Jeffrey; Mkhomawanthu, Chimwemwe; King, Caroline C; Chitsulo, Phindile; Chigwenembe, Maggie; Ellington, Sascha; Hosseinipour, Mina C; Kourtis, Athena P; Chasela, Charles; Tembo, Martin; Tohill, Beth; Piwoz, Ellen G; Jamieson, Denise J; van der Horst, Charles; Adair, Linda

2012-03-01

Breastfeeding increases metabolic demands on the mother, and excessive postnatal weight loss increases maternal mortality. We evaluated the efficacy of a lipid-based nutrient supplement (LNS) for prevention of excess weight loss in breastfeeding, HIV-infected women. The BAN (Breastfeeding, Antiretrovirals, and Nutrition) Study was a randomized controlled trial in Lilongwe, Malawi. At delivery, HIV-infected mothers and their infants were randomly assigned according to a 2-arm (with and without LNS) by 3-arm (maternal triple-antiretroviral prophylaxis, infant-nevirapine prophylaxis, or neither) factorial design. The 28-wk LNS intervention provided daily energy (700 kcal), protein (20 g), and micronutrients (except for vitamin A) to meet lactation needs. Women were counseled to breastfeed exclusively for 24 wk and to wean by 28 wk. Weight change (0-28 wk) was tested in an intent-to-treat analysis by using 2-factor ANOVA and with longitudinal mixed-effects models. At delivery, the LNS (n = 1184) and control (n = 1185) groups had similar mean weights and BMIs. Women receiving the LNS had less 0-28-wk weight loss (-1.97 compared with -2.56 kg, P = 0.003). This difference remained significant after adjustment for maternal antiretroviral drug therapy and baseline BMI. Women receiving antiretroviral drugs had more weight loss than did those not receiving antiretroviral drugs (-2.93 compared with -1.90 kg, P < 0.001). The benefit of the LNS for reducing weight loss was observed both in those receiving antiretroviral drugs (-2.56 compared with -3.32 kg, P = 0.019) and in those not receiving antiretroviral drugs (-1.63 compared with -2.16 kg, P = 0.034). The LNS reduced weight loss among HIV-infected, breastfeeding women, both in those taking maternal antiretroviral prophylaxis to prevent postnatal HIV transmission and in those not receiving antiretroviral prophylaxis. Provision of an LNS may benefit HIV-infected, breastfeeding women in resource-limited settings. This trial was registered at clinicaltrials.gov as NCT00164762.

Breastfeeding: the hidden barrier in Côte d'Ivoire's quest to eliminate mother-to-child transmission of HIV.

PubMed

Buesseler, Heather M; Kone, Ahoua; Robinson, Julia; Bakor, Albert; Senturia, Kirsten

2014-01-01

Côte d'Ivoire has one of the worst HIV/AIDS epidemics in West Africa. This study sought to understand how HIV-positive women's life circumstances and interactions with the public health care system in Bouaké, Côte d'Ivoire, influence their self-reported ability to adhere to antiretroviral prophylaxis during pregnancy. Semistructured interviews were conducted with 24 HIV-positive women not eligible for antiretroviral therapy and five health care workers recruited from four public clinics in which prevention of mother-to-child transmission services had been integrated into routine antenatal care. Self-reported adherence to prophylaxis is high, but women struggle to observe (outdated) guidelines for rapid infant weaning. Women's positive interactions with health providers, their motivation to protect their infants and the availability of free antiretrovirals seem to override most potential barriers to prophylaxis adherence. This study reveals the importance of considering the full continuum of prevention of mother-to-child transmission interventions, including infant feeding, instead of focussing primarily on prophylaxis for the mother and newborn.

Advanced medical countermeasures for radiological accidents and nuclear disasters: prevention, prophylaxis, treatment and pre- and post-exposure management.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

Countermeasures against nuclear terrorism to prevent or limit the number of irradiated human population or radiation intoxications include early identification of the nuclear terrorism event and all persons which exposed by radiation, decontamination program and procedures, radiation control, and medical countermeasures which include medical diagnosis,differential diagnosis of Acute Radiation Syndromes by Immune Enzyme Assay , pre-exposure vaccination with Human Antiradiation Vaccine, post-exposure specific treatment - de-intoxication with Radiation Antidote IgG (blocking Antiradiation Antibodies). Our Advanced Medical Technology elaborated as a part of effective countermeasure include Plan of Action.Countermeasures against nuclear terrorism to prevent or limit the number of high level of lethality and severe forms of radiation illness or intoxications include A.early identification of the nuclear terrorism event and persons exposed,b. appropriate decontamination, c. radiation control, and d.medical countermeasures and medical management of ARS. Medical countermeasures, which include medical interventions such as active immuneprophylaxis with Human Antiradiation Vaccine , passive immune-prophylaxis with Antiradiation Antitoxins immune-globulins IgG , and chemoprophylaxis - post-exposure antioxidants prophylaxis and antibioticprophylaxis. Medical countermeasures with Antiradiation Vaccine should be initiated before an exposure (if individuals are identified as being at high risk for exposure)but after a confirmed exposure event Antiradiation Vaccine not effective and Antiradiation Antidot IgG must be applyed for treatment of Acute Radiation Syndromes.

Willingness to Accept HIV Pre-Exposure Prophylaxis among Chinese Men Who Have Sex with Men

PubMed Central

Li, Shuming; Li, Dongliang; Zhang, Lifen; Fan, Wensheng; Yang, Xueying; Yu, Mingrun; Xiao, Dong; Yan, Li; Zhang, Zheng; Shi, Wei; Luo, Fengji; Ruan, Yuhua; Jin, Qi

2012-01-01

Objective We investigated the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting factors. Methods This study was conducted among MSM in Beijing, China. Study participants, randomly selected from an MSM cohort, completed a structured questionnaire, and provided their blood samples to test for HIV infection and syphilis. Univariate logistic regression analyses were performed to evaluate the factors associated with willingness to accept (WTA) PrEP. Factors independently associated with willingness to accept were identified by entering variables into stepwise logistic regression analysis. Results A total of 152 MSM completed the survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it. Univariate analysis showed that age, years of education, consistent condom use in the past 6 months, heterosexual behavior in the past 6 months, having ever heard of PrEP and the side effects of antiretroviral drugs, and worry about antiretroviral drugs cost were significantly associated with willingness to accept PrEP. In the multivariate logistic regression model, only consistent condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13–0.70) and having ever heard of the side effects of antiretroviral drugs (OR: 0.30; 95% CI: 0.14–0.67) were independently associated with willingness to accept PrEP. Conclusions The awareness of PrEP in the MSM population was low. Sexual behavioral characteristics and knowledge about ART drugs may have effects on willingness to accept PrEP. Comprehensive prevention strategies should be recommended in the MSM community. PMID:22479320

HIV testing, care, and treatment experiences among the steady male partners of female sex workers living with HIV in the Dominican Republic.

PubMed

Fleming, Paul J; Barrington, Clare; Perez, Martha; Donastorg, Yeycy; Kerrigan, Deanna

2016-01-01

Male steady partners of female sex workers (FSW) living with human immunodeficiency virus (HIV) represent a key population for treatment as prevention and/or pre-exposure prophylaxis interventions. This study uses data collected from male steady partners who were referred by FSW living with HIV participating in a multi-level HIV prevention and care intervention in Santo Domingo, Dominican Republic. We conducted a socio-behavioral survey and HIV testing with all men (n = 64) and 16 in-depth interviews with a sub-sample to obtain more depth. Thirty-five of the 64 participants were living with HIV; 27 were previously diagnosed and 8 were diagnosed during our study. As a result, 45% of men were members of sero-discordant sexual partnerships. Of men with no previous HIV diagnosis (n = 37), 15 had never been tested for HIV and nine had not been tested in the past two years. Ninety-three percent of men previously diagnosed with HIV reported receiving HIV care in the past 6 months and 78% were taking anti-retrovirals. Low HIV testing was partly due to men not feeling at risk for HIV, despite having an HIV-infected partner. Additionally, a lack of tailored care inhibited engagement in anti-retroviral treatment for those infected. HIV testing was low, highlighting a need for test-and-treat strategies. Men not living with HIV would benefit from regular testing and would be good candidates for pre-exposure prophylaxis. While almost all men who had been diagnosed with HIV were engaged in care and adherent to anti-retroviral therapy, future research should assess whether they are achieving optimal HIV outcomes for their health and prevention of ongoing transmission.

Previous antiretroviral therapy for prevention of mother-to-child transmission of HIV does not hamper the initial response to PI-based multitherapy during subsequent pregnancy.

PubMed

Briand, Nelly; Mandelbrot, Laurent; Blanche, Stéphane; Tubiana, Roland; Faye, Albert; Dollfus, Catherine; Le Chenadec, Jérôme; Benhammou, Valérie; Rouzioux, Christine; Warszawski, Josiane

2011-06-01

Few data are available on the possible long-term negative effects of a short exposure to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT). To determine whether ART for PMTCT, discontinued after delivery, affects the virological response to highly active antiretroviral therapy (HAART) administered during subsequent pregnancies. All current pregnancies of HIV-1-infected women enrolled in the French Perinatal Cohort (ANRS CO-01 EPF) between 2005 and 2009 and not receiving ART at the time of conception were eligible. We studied the association between history of exposure to ART during a previous pregnancy and detectable viral load (VL) under multitherapy at current delivery (VL ≥ 50 copies/mL). Among 1116 eligible women, 869 were ART naive and 247 had received PMTCT during a previous pregnancy. Previous ART was protease inhibitor (PI)-based HAART in 48%, non-PI-based HAART in 4%, nucleoside reverse transcriptase inhibitor bitherapy in 19% and zidovudine monotherapy in 29% of the women. At current pregnancy, women with or without prior exposure to ART had similar CD4 cell counts and VL before ART initiation. PI-based HAART was initiated in 90% of the women. VL was undetectable (<50 copies/mL) at delivery in 65% of previously ART-naive women, 72% of women previously exposed to HAART, 62% previously exposed to bitherapy, and 67% previously exposed to monotherapy for prophylaxis (P = 0.42). Detectable VL was not associated with previous exposure in multivariate analysis (adjusted OR for previous versus no previous exposure to ART: 0.92; 0.95% confidence interval: 0.59 to 1.44). Efficacy of PI-based combinations is not decreased in women previously exposed to various regimens of antiretroviral PMTCT.

Antiretrovirals and safer conception for HIV-serodiscordant couples

PubMed Central

Matthews, Lynn T.; Smit, Jennifer A.; Cu-Uvin, Susan; Cohan, Deborah

2013-01-01

Purpose of review Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples. Recent findings Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence. Summary For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission. PMID:23032734

Treatment and prevention of HIV infection with long-acting antiretrovirals.

PubMed

Benítez-Gutiérrez, Laura; Soriano, Vicente; Requena, Silvia; Arias, Ana; Barreiro, Pablo; de Mendoza, Carmen

2018-05-01

Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents

PubMed Central

Ramasamy, S; Liu, CQ; Tran, H; Gubala, A; Gauci, P; McAllister, J; Vo, T

2010-01-01

The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin – a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009. PMID:20860656

Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents.

PubMed

Ramasamy, S; Liu, C Q; Tran, H; Gubala, A; Gauci, P; McAllister, J; Vo, T

2010-10-01

The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin - a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009. © 2010 The Commonwealth of Australia. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Rabies post-exposure prophylaxis in travellers returning from Bali, Indonesia, November 2008 to March 2010.

PubMed

Gautret, P; Lim, P L; Shaw, M; Leder, K

2011-03-01

Since 2008, when the outbreak of rabies in Bali began, 45 patients have attended GeoSentinel or EuroTravNet sites for rabies post-exposure prophylaxis (PEP), representing 12.6% of all travellers seen for PEP in all network clinics during the same time period. This suggests that Bali is emerging as a commonly visited destination among travellers presenting for rabies PEP. The data demonstrate that the majority of animal-related injuries in travellers returning from Bali are associated with exposure to monkeys, and not dog bites/scratches. The clinical implications of this are discussed. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Pre-exposure prophylaxis of HIV: A right way to go or a long way to go?

PubMed Central

Yu, Wenya; Wang, Lu; Han, Na; Zhang, Xiayan; Mahapatra, Tanmay; Mahapatra, Sanchita; Babu, Giridhara R.; Tang, Weiming; Detels, Roger; Zhao, Jinkou

2014-01-01

Antiretroviral drugs are being tried as candidates for the pre-exposure prophylaxis (PrEP) against HIV for a considerable period, due to their potential for immediate inhibition of viral replication. Discrepancies in the findings called for a critical review of the relevant efforts and their outcomes. A systematic literature search identified 143 eligible articles of which only 5 reported complete findings while another 11 were still on-going. Observed moderate efficacy and good safety profile seemed to identify PrEP as a promising step for minimizing the spread of HIV to relatively unaffected population and controlling the epidemic among high risk population groups. But the duration of this efficacy was found to depend heavily on the availability, adherence and other related issues like cost, political commitment, ethical consideration etc. To prevent potential cultural and behavioral modifications, proper pre-administration counseling also seemed critical for the success of PrEP as a cost-effective intervention with adequate coverage. PMID:25078629

Barriers to Access and Adoption of Pre-Exposure Prophylaxis for the Prevention of HIV Among Men Who Have Sex With Men (MSM) in a Relatively Rural State.

PubMed

Hubach, Randolph D; Currin, Joseph M; Sanders, Carissa A; Durham, André R; Kavanaugh, Katherine E; Wheeler, Denna L; Croff, Julie M

2017-08-01

Biomedical intervention approaches, including antiretroviral pre-exposure prophylaxis (PrEP), have been demonstrated to reduce HIV incidence among several at-risk populations and to be cost effective. However, there is limited understanding of PrEP access and uptake among men who have sex with men (MSM) residing in relatively rural states. Twenty semistructured interviews were conducted (August-November 2016) to assess opinions of and perceived barriers to accessing and adopting PrEP among MSM residing in Oklahoma. Participants perceived substantial barriers to accessing PrEP including a stigmatizing environment and less access to quality, LGBT-sensitive medical care. Overall, geographic isolation limits access to health providers and resources that support sexual health for Oklahoma MSM. Addressing stigma situated across ecological levels in an effort to increase adoption of PrEP by MSM residing in rural states remains necessary. Without this, social determinants may continue to negatively influence PrEP adoption and sexual health outcomes.

Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

PubMed Central

Delaugerre, Constance; Chaix, Marie-Laure; Blanche, Stephane; Warszawski, Josiane; Cornet, Dorine; Dollfus, Catherine; Schneider, Veronique; Burgard, Marianne; Faye, Albert; Mandelbrot, Laurent; Tubiana, Roland; Rouzioux, Christine

2009-01-01

Background Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns. Patients and Methods We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing. Results Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%): drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10) and neonatal lymphocytes (2/8) suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped. Conclusion This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%), drug resistance was archived in the cellular reservoir and persisted during infancy, with or without antiretroviral treatment. This finding stresses the need for effective antiretroviral treatment of pregnant women. PMID:19765313

Changes in the provision of post-exposure prophylaxis for HIV after sexual exposure following introduction of guidelines and publicity campaigns.

PubMed

Roedling, S; Reeves, I; Copas, A J; Beattie, A; Edwards, S G; Fisher, M; Benn, P

2008-04-01

In July 2004, British Association of Sexual Health and HIV (BASHH) published guidelines for post-exposure prophylaxis following sexual exposure (PEPSE) and the Terence Higgins Trust (THT) launched a campaign promoting PEPSE among men who have sex with men (MSM). We evaluated subsequent changes in PEPSE attendances. Individuals requesting PEPSE in 2004 were identified from clinic databases. Comparisons of clinical data, exposure characteristics and follow-up were made pre and post campaign. Data were available for 197/216 (91%) PEP attendances. The proportion requesting PEP following sexual exposure increased significantly following the campaign. The majority commencing PEPSE were MSM, with the proportion of MSM increasing significantly from 36/46 (78%) pre to 76/80 (95%) following the campaign. Most prescriptions were in high-risk groups and within guidelines. Times to initiation and completion rates were unchanged. Access to PEPSE following the THT campaign and introduction of BASHH guidelines increased. Promotion of earlier initiation of PEPSE and improvement of completion and follow-up is required.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

PubMed Central

Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

2016-01-01

IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. CONCLUSIONS AND RELEVANCE Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults. PMID:27404187

Trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is effective against acute murine inhalational melioidosis and glanders.

PubMed

Barnes, Kay B; Steward, Jackie; Thwaite, Joanne E; Lever, M Stephen; Davies, Carwyn H; Armstrong, Stuart J; Laws, Thomas R; Roughley, Neil; Harding, Sarah V; Atkins, Timothy P; Simpson, Andrew J H; Atkins, Helen S

2013-06-01

Burkholderia pseudomallei is the causative agent of the disease melioidosis, which is prevalent in tropical countries and is intractable to a number of antibiotics. In this study, the antibiotic co-trimoxazole (trimethoprim/sulfamethoxazole) was assessed for the post-exposure prophylaxis of experimental infection in mice with B. pseudomallei and its close phylogenetic relative Burkholderia mallei, the causative agent of glanders. Co-trimoxazole was effective against an inhalational infection with B. pseudomallei or B. mallei. However, oral co-trimoxazole delivered twice daily did not eradicate infection when administered from 6h post exposure for 14 days or 21 days, since infected and antibiotic-treated mice succumbed to infection following relapse or immunosuppression. These data highlight the utility of co-trimoxazole for prophylaxis both of B. pseudomallei and B. mallei and the need for new approaches for the treatment of persistent bacterial infection. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Can we afford to offer pre-exposure prophylaxis to MSM in Catalonia? Cost-effectiveness analysis and budget impact assessment.

PubMed

Reyes-Urueña, J; Campbell, C; Diez, E; Ortún, V; Casabona, J

2018-06-01

Pre-exposure prophylaxis (PrEP) effectiveness has been well established. This study aims to assess the cost-effectiveness of providing PrEP, estimate the number of eligible MSM, and its budget impact in Catalonia. Cost-effectiveness analysis compared costs of on daily basis and "on demand" PrEP to prevent one infection with lifetime costs of one HIV infection. We estimated the total cost of providing PrEP by estimating number of eligible MSM, and included in the budget impact assessment antiretroviral and laboratory costs. Costs were lower for the on-demand PrEP group by €64015.1 and the incremental benefit was nearly 15 life-years and 17 quality-adjusted life-years gained. The incremental cost-effectiveness ratio (ICER) was cost-effective at €6281.62 when undiscounted PrEP was given daily. On-demand PrEP can be considered cost-saving in 20 years if the price is reduced by 90%. The number of eligible MSM in Catalonia ranges from 5,989 to 10,972. At current antiretroviral costs, the annual cost would range between €25.3-46.7 million/year (on demand PrEP), and €42.9-78.7 million/year (daily basis PrEP). PrEP is most cost-effective if targeted towards groups with high incidence rates of over 3%/year. Beneficial ICER depends on reducing the current price of Truvada® and ensuring that effectiveness is maintained at high levels.

Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review

PubMed Central

Oliveira, Natalia Mejias; Ferreira, Felipe Augusto Yamauti; Yonamine, Raquel Yumi; Chehter, Ethel Zimberg

2014-01-01

ABSTRACT In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes. PMID:24728257

Foreign Humanitarian Assistance

DTIC Science & Technology

2009-03-17

based products and is adequate for the widest range of cultural or religious dietary restrictions. HDR will maintain the health of moderately...rehydration, fortified nutritional products, and micronutrient supplements; provide post- rape-care kits, including post-exposure prophylaxis for human

Occupational Exposure to HIV: Advice for Health Care Workers

MedlinePlus

... kidney, and bone marrow function. Another option is post-exposure prophylaxis (PEP). This treatment suppresses the HIV virus to prevent infection. If you still test positive, the treatment can help decrease the virus’ ...

Occupational exposure to blood and body fluids: new postexposure prophylaxis recommendations. United States Occupational Safety and Health Administration.

PubMed

Cuny, E; Carpenter, W M

1998-04-01

Dental health care professionals continue to suffer exposure incidents from instruments contaminated with blood and/or body fluids from patients. Each of these cases requires that a rigid protocol be followed for their evaluation. New information regarding the risk factors for HIV-seroconversion following an exposure incident have been identified. Recent data has demonstrated that a 79 percent reduction in disease transmission may be possible with a new combination drug therapy. The anti-retroviral drugs included in this new regimen are now standard in the management of occupational exposure to HIV. Several factors set dentistry apart from other health care occupations, and these differences appear to have an effect on the risks associated with occupational exposures. This article explores these risk factors and the new recommendations for postexposure care.

Use of combination neonatal prophylaxis for the prevention of mother-to-child transmission of HIV infection in European high-risk infants.

PubMed

Chiappini, Elena; Galli, Luisa; Giaquinto, Carlo; Ene, Luminita; Goetghebuer, Tessa; Judd, Ali; Lisi, Catiuscia; Malyuta, Ruslan; Noguera-Julian, Antoni; Ramos, Jose Tomas; Rojo-Conejo, Pablo; Rudin, Christoph; Tookey, Pat; de Martino, Maurizio; Thorne, Claire

2013-03-27

To evaluate use of combination neonatal prophylaxis (CNP) in infants at high risk for mother-to-child transmission (MTCT) of HIV in Europe and investigate whether CNP is more effective in preventing MTCT than single drug neonatal prophylaxis (SNP). Individual patient-data meta-analysis across eight observational studies. Factors associated with CNP receipt and with MTCT were explored by logistic regression using data from nonbreastfed infants, born between 1996 and 2010 and at high risk for MTCT. In 5285 mother-infant pairs, 1463 (27.7%) had no antenatal or intrapartum antiretroviral prophylaxis, 915 (17.3%) had only intrapartum prophylaxis and 2907 (55.0%) mothers had detectable delivery viral load despite receiving antenatal antiretroviral therapy. Any neonatal prophylaxis was administered to 4623 (87.5%) infants altogether; 1105 (23.9%) received CNP. Factors significantly associated with the receipt of CNP were later calendar birth year, no elective caesarean section, maternal CD4 cell count less than 200 cells/μl, maternal delivery viral load more than 1000 copies/ml, no antenatal antiretroviral therapy, receipt of intrapartum single-dose nevirapine and cohort. After adjustment, absence of neonatal prophylaxis was associated with higher risk of MTCT compared to neonatal prophylaxis [adjusted odds ratio (aOR) 2.29; 95% confidence interval (95% CI) 1.46-2.59; P < 0.0001]. Further, there was no association between CNP and MTCT compared to SNP (aOR 1.41; 95% CI 0.97-2.5; P = 0.07). In this European population, CNP use is increasing and associated with presence of MTCT risk factors. The finding of no observed difference in MTCT risk between one drug and CNP may reflect residual confounding or the fact that CNP may be effective only in a subgroup of infants rather than the whole population of high-risk infants.

Challenges and potential barriers to the uptake of antiretroviral-based prevention in Asia and the Pacific region.

PubMed

Lo, Ying-Ru; Kato, Masaya; Phanuphak, Nittaya; Fujita, Masami; Duc, Duong Bui; Sopheap, Seng; Pendse, Razia; Yu, Dongbao; Wu, Zunyou; Chariyalertsak, Suwat

2014-07-01

Evidence has emerged over the past few years on the effectiveness of antiretroviral-based prevention technologies to prevent (i) HIV transmission while decreasing morbidity and mortality in HIV-infected persons, and (ii) HIV acquisition in HIV-uninfected individuals through pre-exposure prophylaxis (PrEP). Only few of the planned studies on treatment as prevention (TasP) are conducted in Asia. TasP might be more feasible and effective in concentrated rather than in generalised epidemics, as resources for HIV testing and antiretroviral treatment could focus on confined and much smaller populations than in the generalised epidemics observed in sub-Saharan Africa. Several countries such as Cambodia, China, Thailand and Vietnam, are now paving the way to success. Similar challenges arise for both TasP and PrEP. However, the operational issues for PrEP are amplified by the need for frequent retesting and ensuring adherence. This paper describes challenges for the implementation of antiretroviral-based prevention and makes the case that TasP and PrEP implementation research in Asia is much needed to provide insights into the feasibility of these interventions in populations where firm evidence of 'real world' effectiveness is still lacking.

Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure

PubMed Central

Palumbo, Paul; Lindsey, Jane C.; Hughes, Michael D.; Cotton, Mark F.; Bobat, Raziya; Meyers, Tammy; Bwakura-Dangarembizi, Mutsawashe; Chi, Benjamin H.; Musoke, Philippa; Kamthunzi, Portia; Schimana, Werner; Purdue, Lynette; Eshleman, Susan H.; Abrams, Elaine J.; Millar, Linda; Petzold, Elizabeth; Mofenson, Lynne M.; Jean-Philippe, Patrick; Violari, Avy

2010-01-01

BACKGROUND Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. METHODS We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. RESULTS A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. CONCLUSIONS Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.) PMID:20942667

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

PubMed

Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

2015-12-10

The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

LepVax, a defined subunit vaccine that provides effective pre-exposure and post-exposure prophylaxis of M. leprae infection.

PubMed

Duthie, Malcolm S; Pena, Maria T; Ebenezer, Gigi J; Gillis, Thomas P; Sharma, Rahul; Cunningham, Kelly; Polydefkis, Michael; Maeda, Yumi; Makino, Masahiko; Truman, Richard W; Reed, Steven G

2018-01-01

Sustained elimination of leprosy as a global health concern likely requires a vaccine. The current standard, BCG, confers only partial protection and precipitates paucibacillary (PB) disease in some instances. When injected into mice with the T helper 1 (Th1)-biasing adjuvant formulation Glucopyranosyl Lipid Adjuvant in stable emulsion (GLA-SE), a cocktail of three prioritized antigens (ML2055, ML2380 and ML2028) reduced M. leprae infection levels. Recognition and protective efficacy of a single chimeric fusion protein incorporating these antigens, LEP-F1, was confirmed in similar experiments. The impact of post-exposure immunization was then assessed in nine-banded armadillos that demonstrate a functional recapitulation of leprosy. Armadillos were infected with M. leprae 1 month before the initiation of post-exposure prophylaxis. While BCG precipitated motor nerve conduction abnormalities more rapidly and severely than observed for control infected armadillos, motor nerve injury in armadillos treated three times, at monthly intervals with LepVax was appreciably delayed. Biopsy of cutaneous nerves indicated that epidermal nerve fiber density was not significantly altered in M. leprae -infected animals although Remak Schwann cells of the cutaneous nerves in the distal leg were denser in the infected armadillos. Importantly, LepVax immunization did not exacerbate cutaneous nerve involvement due to M. leprae infection, indicating its safe use. There was no intraneural inflammation but a reduction of intra axonal edema suggested that LepVax treatment might restore some early sensory axonal function. These data indicate that post-exposure prophylaxis with LepVax not only appears safe but, unlike BCG, alleviates and delays the neurologic disruptions caused by M. leprae infection.

[Recommendations for non-occupational postexposure HIV prophylaxis. Spanish Working Group on Non-Occupational Postexposure HIV Prophylaxis of the Catalonian Center for Epidemiological Studies on AIDS and the AIDS Study Group].

PubMed

Almeda, Jesús; Casabona, Jordi; Allepuz, Alejandro; García-Alcaide, Felipe; del Romero, Jorge; Tural, Cristina; Colm, Joan; Bolao, Ferrán; Campins, Magda; Domínguez, Angela; Force, Lluís; Giménez, Albert; Guerra-Romero, Luis

2002-10-01

Evidence is lacking on the possible efficacy and effectiveness of non-occupational postexposure prophylaxis (PEP). However, because of its biological plausibility, the use of antiretroviral (ARV) drugs to prevent the development of infection in certain cases of accidental or sporadic exposure has begun to be considered as common clinical practice. Previous studies performed in Spain have demonstrated both the demand and the prescription of ARV as PEP and especially the diversity and inconsistency in the criteria used. In this context, in April of 2000 the Centre for Epidemiological Studies on AIDS of Catalonia (CEESCAT) (Department of Health and Social Security of the Autonomous Government of Catalonia), in collaboration with the National AIDS Plan and the AIDS Study Group (GESIDA), promoted the creation of a working group for the drafting of recommendations for PEP against HIV outside the occupational health context. The recommendations have been made bearing in mind the exceptional character of the exposure, the time elapsed since exposure, as well as evaluation of the risk of infection according to the type of exposure and the information available on the source of infection. In addition, the recommendations include the immediate measures necessary, as well as the preventive measures and clinical follow-up required both for HIV and for other infectious agents. All PEP regimens should be started within 72 hours of exposure and appropriate daily doses of two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI), or two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTIs), should be administered for four weeks, bearing in mind the pharmacological and clinical situation of the source person. These recommendations should be updated periodically.

Differences in knowledge, attitudes and behaviors of Israeli HIV-uninfected gay men in HIV-discordant vs. concordant steady relationships.

PubMed

Tairy, Daniel; Levy, Itzchak; Turner, Dan; Livnat, Yuval; Mor, Zohar

2018-06-01

HIV-discordant gay male couples may play an important role in HIV-transmissions. This cross-sectional study compared the knowledge, attitudes and sexual behaviors of HIV-uninfected gay men, between those in HIV-discordant and those in HIV-concordant steady relationships. Anonymous questionnaires were distributed electronically in designated gay-related internet sites and in AIDS-clinics in 2015. The dependent variable was defined as a steady relationship of an HIV-uninfected man with an HIV-infected partner. Risky sexual behavior was defined as unprotected anal intercourse (UAI) with a sex partner whose HIV-status was either positive or unknown. Of 2,319 responders, 460 (20%) were HIV-uninfected gay men in steady relationships, of whom 72 were in HIV-discordant relationships and 388 were in HIV-concordant relationships. Those in HIV-discordant relationships presented better established knowledge regarding HIV-transmission, more lenient attitudes regarding UAI, and reported being involved in riskier sexual behavior, both within and outside their steady relationship compared to men in HIV-concordant relationships. UAI was performed by 48% of the HIV-discordant couples and was associated with the use of sero-positioning strategy and with achieving undetectable viral-load. These findings reflect the complexity of constant use of condoms during long-term sero-discordant relationships. Targeted interventions for HIV-prevention in HIV-discordant couples should be employed for balancing the partners' desire for intimacy and sexual pleasure in the relationship, while reducing the risk for acquiring HIV. ART: Antiretroviral therapy; PEP: Post exposure prophylaxis; PrEP: Pre exposure prophylaxis; STI: Sexually transmitted infections; UAI: Unprotected anal intercourse.

The rationale for the use of measles post-exposure prophylaxis in pregnant women: a review.

PubMed

Manikkavasagan, G; Ramsay, M

2009-10-01

A review of published literature was undertaken to investigate the maternal and fetal effects of measles infection in pregnancy and to inform the need for post-exposure prophylaxis. There is no evidence to support an association between measles in pregnancy and congenital defects. However, the need for effective post-exposure protection is supported by studies suggesting a high risk of severe maternal morbidity, fetal loss and prematurity. Measles in late pregnancy can also lead to perinatal infection in the infant, which may be associated with a high mortality and the risk of subacute sclerosing panencephalitis. UK guidance recommends using human normal immunoglobulin for susceptible pregnant women exposed to measles. Although there is no direct evidence that this will reduce the complications of measles in pregnancy, it may attenuate disease and therefore reduce the rate of complications. Measures to identify women likely to be susceptible include assessment of age, vaccination history, and/or antibody testing.

PrEP Whores and HIV Prevention: The Queer Communication of HIV Pre-Exposure Prophylaxis (PrEP).

PubMed

Spieldenner, Andrew

2016-12-01

HIV pre-exposure prophylaxis (PrEP) has been introduced as another biomedical tool in HIV prevention. Whereas other such tools-including post-exposure prophylaxis (PEP) and interruption of perinatal transmission-have been embraced by those impacted by HIV, PrEP has been met with more conflict, especially within the gay community and HIV organizations. The "PrEP whore" has come to designate the social value and personal practices of those taking PrEP. This study examines the "PrEP whore" discourse by using queer theory and quare theory. Within these theoretical vantage points, the study explicates four discursive areas: slut shaming, dirty/clean binaries, mourning the loss of condoms, and reclaiming the inner whore. The study illuminates possible discursive strategies that lie outside of the domains of public health and within the individual and community.

Awareness and Willingness to Use Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men and Transgender Women in Brazil.

PubMed

Hoagland, Brenda; De Boni, Raquel B; Moreira, Ronaldo I; Madruga, José Valdez; Kallas, Esper G; Goulart, Silvia Pereira; Cerqueira, Natalia; Torres, Thiago S; Luz, Paula M; Fernandes, Nilo Martinez; Liu, Albert Y; Grinsztejn, Beatriz; Veloso, Valdilea G

2017-05-01

Antiretroviral pre-exposure prophylaxis (PrEP) is recommended to prevent HIV infection among high-risk men who have sex with men (MSM) though not available in Brazil where the HIV epidemic persists unabated in this group. This cross-sectional study describes PrEP awareness and willingness and associated factors among MSM and transvestite/transgender women (trans women) pre-screened for the PrEP Brasil study. Awareness was reported by 61.3 % of the participants and was associated with age, education, site, study period and prior HIV testing. Most participants (82.1 %) were willing to use PrEP, which was associated with site, study period, number of male condomless anal sexual partners and anal sex with HIV positive/unknown partners. PrEP information is need among young and less educated individuals. Willingness to use PrEP was high and future studies should be conducted to confirm PrEP acceptability and the characteristics of the population who chose to adopt this intervention.

Executive summary: Pre-exposure prophylaxis for prevention of HIV infection in adults in Spain: July 2016.

PubMed

Moreno, Santiago; Antela, Antonio; García, Felipe; Del Amo, Julia; Boix, Vicente; Coll, Pep; Fortuny, Claudia; Sirvent, Juan L Gómez; Gutiérrez, Félix; Iribarren, José A; Llibre, Josep M; Quirós, Juan C López Bernaldo de; Losa, Juan Emilio; Lozano, Ana; Meulbroek, Michael; Olalla, Julián; Pujol, Ferran; Pulido, Federico; Crespo Casal, Manuel; García, Juan González; Aldeguer, José López; Molina, Jose A Pérez; Podzamczer Palter, Daniel; Román, Antonio Rivero

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

[PrEP Forum: an on-line debate on pre-exposure prophylaxis in Brazil].

PubMed

Queiroz, Artur Acelino Francisco Luz Nunes; Sousa, Alvaro Francisco Lopes de

2017-11-21

This study aimed to identify health-promoting contents focused on HIV/Aids prevention in messages posted in a Facebook group for debates on the use of pre-exposure prophylaxis (PrEP). This was a prospective observational study using systematic non-participant observation. From July 2015 to June 2016, all the posts in the group were catalogued and formed a corpus. Everything was processed in IRaMuTeQ and analyzed by descending hierarchical classification. The collected data were grouped in three classes: (1) HIV/Aids prevention: discussing prophylaxis, treatment, target public, and side effects; (2) universal access to PrEP in Brazil: discussing government responsibilities; (3) on-line purchase of truvada: exposing a situation of vulnerability. The findings call attention to a potential public health problem and provide backing for understanding facilitators and barriers to the use of PrEP in Brazil through the identification of health-promoting content linked to individual, social, and institutional markers.

Blood safety implications of donors using HIV pre-exposure prophylaxis.

PubMed

Seed, C R; Yang, H; Lee, J F

2017-07-01

HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection. The most commonly used PrEP medication (Truvada ® , Gilead Sciences, Inc.) acts by inhibiting HIV-1 reverse transcriptase. If someone who is using PrEP unknowingly becomes HIV infected (termed 'PrEP breakthrough infection'), there may be suppressed viral replication resulting in a virus level undetectable by the most sensitive HIV NAT. Failure to seroconvert and seroreversion (loss of previously detectable HIV antibodies) have also both been observed with 2nd, 3rd and 4th generation screening immunoassays, as well as Western blot assays. If such a person was tested in the course of donating blood, the results may therefore be difficult to interpret. The index of suspicion for possible PrEP 'interference' should be highest in the context of concomitant low-level positive or 'greyzone' reactivity on HIV NAT and serological tests, which is an unusual pattern in acutely HIV-infected blood donors. Another possibility is detectable HIV RNA with negative HIV serology (i.e. a potential 'NAT yield' case) but without subsequent HIV seroconversion (or disappearance of HIV RNA). Excluding antiretroviral therapy or PrEP use by the donor in such circumstances would be important. The current rarity of PrEP breakthrough infection indicates that any potential safety risk is likely very small. However, considering the increasing use of PrEP we feel it is prudent for those interpreting HIV donor screening test results to consider the potential for PrEP interference. © 2017 International Society of Blood Transfusion.

SEXUAL PRACTICES AMONG MEN WHO HAVE SEX WITH MEN IN CHIANG MAI, THAILAND: PART OF THE ANTIRETROVIRAL PRE-EXPOSURE PROPHYLAXIS TRIAL.

PubMed

Tangmunkongvorakul, Arunrat; Chariyalertsak, Suwat; Amico, K Rivet; Guptarak, Marisa; Saokhieo, Pongpun; Sangangamsakun, Thirayut; Songsupa, Radchanok; McMahan, Vanessa; Grant, Robert

2016-05-01

This study aimed to gain a better understanding of the association between participation in a blinded antiretroviral pre-exposure prophylaxis (PrEP) clinical trial and sexual practices among men who have sex with men and transgender women. This study utilized both quantitative and qualitative methodologies. Data included reported PrEP medication adherence and sexual behavior among 114 study participants. Forty-six participants took part in qualitative data collection, 32 were interviewed and 14 participated in one of three focus group discussions. The average percentage of study medication adherence, number of sex partners and rates of sex without a condom were calculated. For qualitative data, content analysis was used to identify repeated normative themes, some of which arose spontaneously from interview interactions. Participants at the Chiang Mai site reported good adherence to the study medication. The sexual risk behavior of these participants had decreased by their final study visit; this was unrelated to level of adherence. Qualitative findings describe sexual practices that were highly contextual; participants used risk assessments to determine sex practices. Condoms were used with casual partners but not necessarily with primary partners. Our findings suggest that while PrEP is an exciting new development for HIV prevention, it must be paired with behavioral interventions to fully address sexual risk among this population. Interventions should provide this population with skills to negotiate condom use with their primary partners as well as in situations in which their sexual partners do not support condom use.

Counseling Framework for HIV-Serodiscordant Couples on the Integrated Use of Antiretroviral Therapy and Pre-exposure Prophylaxis for HIV Prevention.

PubMed

Morton, Jennifer F; Celum, Connie; Njoroge, John; Nakyanzi, Agnes; Wakhungu, Imeldah; Tindimwebwa, Edna; Ongachi, Snaidah; Sedah, Eric; Okwero, Emmanuel; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Haberer, Jessica E; Baeten, Jared M; Heffron, Renee

2017-01-01

For HIV-serodiscordant couples, integrated delivery of antiretroviral therapy (ART) for HIV-positive partners and time-limited pre-exposure prophylaxis (PrEP) for negative partners virtually eliminates HIV transmission. Standardized messaging, sensitive to the barriers and motivators to HIV treatment and prevention, is needed for widespread scale-up of this approach. Within the Partners Demonstration Project, a prospective interventional project among 1013 serodiscordant couples in Kenya and Uganda, we offered ART to eligible HIV-positive partners and PrEP to HIV-negative partners before ART initiation and through the HIV-positive partner's first 6 months of ART use. We conducted individual and group discussions with counseling staff to elicit the health communication framework and key messages about ART and PrEP that were delivered to couples. Counseling sessions for serodiscordant couples about PrEP and ART included discussions of HIV serodiscordance, PrEP and ART initiation and integrated use, and PrEP discontinuation. ART messages emphasized daily, lifelong use for treatment and prevention, adherence, viral suppression, resistance, side effects, and safety of ART during pregnancy. PrEP messages emphasized daily dosing, time-limited PrEP use until the HIV-positive partner sustained 6 months of high adherence to ART, adherence, safety during conception, side effects, and other risks for HIV. Counseling messages for HIV-serodiscordant couples are integral to the delivery of time-limited PrEP as a "bridge" to ART-driven viral suppression. Their incorporation into programmatic scale-up will maximize intervention impact on the global epidemic.

Knowledge, attitudes, and beliefs about HIV pre-exposure prophylaxis among US Air Force Health Care Providers

PubMed Central

Hakre, Shilpa; Blaylock, Jason M; Dawson, Peter; Beckett, Charmagne; Garges, Eric C; Michael, Nelson L; Danaher, Patrick J; Scott, Paul T; Okulicz, Jason F

2016-01-01

Abstract Providers are central to effective implementation of HIV pre-exposure prophylaxis (PrEP). Primary care providers (PCP) and infectious disease physicians (ID) in the US Air Force (USAF) participated in a cross-sectional survey regarding knowledge, attitudes, and beliefs toward HIV PrEP. Characteristics associated with PrEP knowledge were assessed in univariate and multivariate analyses. Among 403 (40% of 1015 providers) participants, 9% (PCP 383, ID 20) ever prescribed PrEP. In univariate analysis, years in practice, number of HIV-infected patients treated in the past 12 months, past prescription of antiretrovirals for HIV prevention, frequency of prescribing PrEP in the past 12 months, and ever being questioned by a patient about PrEP were associated with PrEP knowledge (P < 0.05). In multivariate analysis, providers who had ever prescribed antiretrovirals to prevent HIV (AOR: 2.37, 95% CI: 1.27–4.42) had greater odds of high PrEP knowledge. Despite concerns about medication side effects (overall 67%: PCP 68%, ID 85%) and prescribing PrEP without clear evidence (overall 60%: PCP 65%, ID 62%), 64% (PCP 65%, ID 85%) of participants indicated PrEP should be offered in the Military Health System and 68% (PCP 70%, ID 100%) disagreed with the statement that their patient population was not at risk for HIV infection. Successful PrEP implementation in the USAF will require continued education and training of primary care providers to improve knowledge and mitigate concerns about PrEP. PMID:27512869

Higher placental anti-inflammatory IL-10 cytokine expression in HIV-1 infected women receiving longer zidovudine prophylaxis associated with nevirapine.

PubMed

Pornprasert, Sakorn; Mary, Jean-Yves; Faye, Albert; Leechanachai, Pranee; Limtrakul, Aram; Rugpao, Sungwal; Sirivatanapa, Pannee; Gomuthbutra, Vorapin; Matanasaravoot, Wanmanee; Le Coeur, Sophie; Lallemant, Marc; Barré-Sinoussi, Françoise; Menu, Elisabeth; Ngo-Giang-Huong, Nicole

2009-03-01

Placental cytokine balance may be critical for the control of mother-to-child transmission (MTCT) of HIV. We assessed whether the type and duration of antiretrovirals used for prevention of HIV-1-MTCT modified the inflammatory cytokine profile. We investigated the levels of cytokine expression in the placentas of 61 HIV-1-infected women who received zidovudine (ZDV) plus single dose nevirapine (SD-NVP) or ZDV only for prevention of MTCT. Placentas of 38 HIV-1-uninfected women were included as controls. All placentas were obtained after vaginal delivery. Levels of mRNA and cytokine expression were quantified using real-time PCR and ELISA, respectively, in placental explants and 24-hour culture supernatants and analyzed in relation to the women's characteristics and the type and duration of antiretroviral prophylaxis. HIV-1-infected and uninfected women did not show any differences in the expression of placental cytokine secretion except for a trend toward lower TNF-alpha mRNA levels in HIV-1-infected women. Within the HIV-1-infected group, women who were exposed to a long duration of ZDV (>72 days) or received SD-NVP less than 5h prior to delivery, more frequently expressed detectable levels of IL-10 in their placentas (32% versus 7% (p = 0.01) and 32% versus 5% (p = 0.02), respectively). No infant was found to be HIV-1-infected. Our results showed a normalization of the placental cytokine balance in HIV-1-infected women receiving antiretroviral prophylaxis. Furthermore, the type and duration of antiretroviral prophylaxis have an impact on the placental anti-inflammatory IL-10 expression level, which may contribute to controlling HIV replication at the placental level, thus reducing MTCT of HIV-1.

Topical Prophylaxis for HIV Prevention in Women: Becoming a Reality

PubMed Central

Verma, Natasha A.; Lee, Anna C.; Herold, Betsy C.

2011-01-01

Strategies to protect against sexual transmission of HIV include the development of products formulated for topical application, which limit the toxicities associated with systemic oral pre-exposure prophylaxis. Following several clinical trial failures, attention is now focused on antiretroviral (ARV) agents. Highly potent ARV topical formulations provide a female-controlled, targeted, and feasible option for HIV prevention. A recently completed tenofovir gel trial was the first to demonstrate significant protection against HIV acquisition. Topical ARVs have the advantage of delivering high concentration of drug at the site of transmission of HIV, with low systemic absorption. Sustained-release formulations, such as intravaginal rings, will likely improve adherence and can be designed to provide controlled and continuous delivery of ARV combinations. Further studies to test alternative dosing strategies and pharmacokinetic/pharmacodynamic relationships in the genital tract will provide valuable information as the field strives to improve upon the promising tenofovir gel trial results. PMID:21424725

Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2018).

PubMed

2018-05-11

This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017. 1 The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisions. The main difference with respect to the previous document concerns recommended initial ART regimens, only three of which are maintained as preferential. All three include dolutegravir or raltegravir, together with emtricitabine/tenofovir alafenamide or abacavir/lamivudine. Other differences concern the section on switching ART in patients with suppressed viral replication, which now includes new two- and three-drug regimens, and the antiretroviral drugs recommended for pregnant women and patients with tuberculosis. A recommendation has also been added for patients who present with acute HIV infection after pre-exposure prophylaxis. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Transitioning to HIV Pre-Exposure Prophylaxis (PrEP) from Non-Occupational Post-Exposure Prophylaxis (nPEP) in a Comprehensive HIV Prevention Clinic: A Prospective Cohort Study.

PubMed

Siemieniuk, Reed A C; Sivachandran, Nirojini; Murphy, Pauline; Sharp, Andrea; Walach, Christine; Placido, Tania; Bogoch, Isaac I

2015-08-01

The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality.

A review of nanotechnological approaches for the prophylaxis of HIV/AIDS

PubMed Central

Date, Abhijit A.; Destache, Christopher J.

2013-01-01

Successful treatment and control of HIV/AIDS is one of the biggest challenges of 21st century. More than 33 million individuals are infected with HIV worldwide and more than 2 million new cases of HIV infection have been reported. The situation demands development of effective prevention strategies to control the pandemic of AIDS. Due to lack of availability of an effective HIV vaccine, antiretroviral drugs and nucleic acid therapeutics like siRNA have been explored for HIV prophylaxis. Clinical trials shave shown that antiretroviral drugs, tenofovir and emtricitabine can offer some degree of HIV prevention. However, complete prevention of HIV infection has not been achieved yet. Nanotechnology has brought a paradigm shift in the diagnosis, treatment and prevention of many diseases. The current review discusses potential of various nanocarriers such as dendrimers, polymeric nanoparticles, liposomes, lipid nanocarriers, drug nanocrystals, inorganic nanocarriers and nanofibers in improving efficacy of various modalities available for HIV prophylaxis. PMID:23726227

Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013).

PubMed

2013-11-01

In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is <500cells/μL; if the CD4(+) lymphocyte count is >500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >10(5)copies/mL, CD4(+) lymphocyte percentage <14%, cognitive impairment, and age >55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Cost-effectiveness of rabies post exposure prophylaxis in Iran.

PubMed

Hatam, Nahid; Esmaelzade, Firooz; Mirahmadizadeh, Alireza; Keshavarz, Khosro; Rajabi, Abdolhalim; Afsar Kazerooni, Parvin; Ataollahi, Marzieh

2014-01-01

The rabies is one of the most important officially-known viral zoonotic diseases for its global distribution, outbreak, high human and veterinary costs, and high death rate and causes high economic costs in different countries of the world every year. The rabies is the deadliest disease and if the symptoms break out in a person, one will certainly die. However, the deaths resulting from rabies can be prevented by post-exposure prophylaxis. To do so, in Iran and most of the countries in the world, all the people who are exposed to animal bite receive Post-Exposure Prophylaxis (PEP) treatment. The present survey aimed to investigate the cost-effectiveness of PEP in southern Iran. The present study estimated the PEP costs from the government`s Perspective with step-down method for the people exposed to animal bite, estimated the number of DALYs prevented by PEP in the individuals using decision Tree model, and computed the Incremental cost-effectiveness Ratio. The information collected of all reported animal bite cases (n=7111) in Fars Province, who referred rabies registries in urban and rural health centers to receive active care. Performing the PEP program cost estimated 1,052,756.1 USD for one  year and the estimated cost for the treatment of each animal bite case and each prevented death was 148.04 and 5945.42 USD, respectively. Likewise 4,509.82 DALYs were prevented in southern Iran in 2011 by PEP program. The incremental cost-effectiveness ratio for each DALY was estimated to be 233.43 USD. In addition to its full effectiveness in prophylaxis from rabies, PEP program saves the financial resources of the society, as well. This study showed performing PEP to be more cost-effective.

Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database

PubMed Central

2012-01-01

Background Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits. PMID:22281054

Safety of discontinuing cotrimoxazole prophylaxis among HIV infected adults on anti-retroviral therapy in Uganda (COSTOP trial): Design.

PubMed

Anywaine, Zacchaeus; Abaasa, Andrew; Levin, Jonathan; Kasirye, Ronnie; Kamali, Anatoli; Grosskurth, Heiner; Munderi, Paula; Nunn, Andrew

2015-07-01

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design. COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm(3) are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events. Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations. This paper describes the design and methodological considerations important for the conduct of CTX cessation studies. Copyright © 2015. Published by Elsevier Inc.

The potential of targeted antibody prophylaxis in SARS outbreak control: a mathematic analysis.

PubMed

Bogaards, Johannes Antonie; Putter, Hein; Jan Weverling, Gerrit; Ter Meulen, Jan; Goudsmit, Jaap

2007-03-01

Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak. We developed a mathematical model to investigate the effects of hospital admission and targeted antibody prophylaxis on the reproduction number R, defined as the number of secondary cases generated by an index case, during different SARS outbreak scenarios. Assuming a basic reproduction number R(0)=3, admission of patients to hospital within 4.3 days of symptom onset is necessary to achieve outbreak control without the need to further reduce community-based transmission. Control may be enhanced by providing pre-exposure prophylaxis to contacts of hospitalized patients, and through contact tracing and provision of post-exposure prophylaxis. Antibody prophylaxis may also be employed to reduce R below one and thereby restrict outbreak size and duration. Patient isolation alone can be sufficient to control SARS outbreaks provided that the time from onset to admission is short. Antibody prophylaxis as supplemental measure generally allows for containment of higher R(0) values and restricts both the size and duration of an outbreak.

The use of antiretroviral therapy for the prevention of new HIV infection in populations at high risk for HIV sero-conversion in Nigeria.

PubMed

Idoko, John; Folayan, Morenike O

2014-09-01

The last few years have witnessed a renewed commitment to HIV prevention. The evidence to support the use of antiretroviral therapy (ART) for prevention of new HIV infection in the form of Pre-exposure prophylaxis (PrEP) among men who have sex with men, transgender, people who inject drugs, heterosexual men and women and HIV-1 serodiscordant couples, or treatment as prevention (TasP) for serodiscordant couples have also grown. The need to explore the possible use of ART for HIV prevention in Nigeria has become imperative in view of its high HIV burden and the current slow pace of effort to achieve the universal target of reducing its HIV incidence by 50%. While PrEP and TasP are welcome addendum to the existing HIV prevention armamentarium, it is still important to conduct a demonstration project to identify strategies that can facilitate access to PrEP and TasP taking cognizance of the peculiar local challenges with respect to ART and HIV prevention commodity access. The country has therefore drawn a roadmap for itself on how to introduce ART for use for HIV prevention as either PrEP or TasP. This paper discusses the three year national roadmap that would enable the country generated the needed scientific evidence as well as extensive community support for use of ART for HIV prevention in Nigeria. This process includes the conduct of modeling and formative studies, and the implementation of a 24 months demonstration project. The outcome of the demonstration project would inform plans for the scale up of pre-exposure prophylaxis (PrEP) access for population(s) at high risk for HIV infection in Nigeria.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention.

PubMed

Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention

PubMed Central

Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Introduction Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. Discussion After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. Conclusions The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV. PMID:26198341

MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters.

PubMed

Gowen, Brian B; Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Nishiyama, Shoko; Wandersee, Luci; Scharton, Dionna; Jung, Kie-Hoon; Ikegami, Tetsuro

2015-01-01

Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.

Pre-exposure prophylaxis of HIV

PubMed Central

Naswa, Smriti; Marfatia, Y. S.

2011-01-01

Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other prevention strategies. Women represent nearly 60% of adults infected with HIV and PrEP can be a female-controlled prevention method for women who are unable to negotiate condom use. Two antiretroviral nucleoside analog HIV-1 reverse transcriptase inhibitor drugs are currently under trial as PrEP drugs, namely tenofovirdisoproxilfumarate (TDF) alone and TDF in combination with emricitabine (FTC), to be taken as daily single dose oral drugs. There are 11 ongoing trials of ARV-based prevention in different at risk populations across the world. The iPrex trial showed that daily use of oral TDF/FTC by MSM resulted in 44% reduction in the incidence of HIV. This led to publication of interim guidance by CDC to use of PrEP by health providers for MSM. Few other trials are Bangkok Tenofovir Study, Partners PrEP Study, FEM-PrEP study, and VOICE (MTN-003) study. Future trials are being formulated for intermittent PrEP (iPrEP) where drugs are taken before and after sex, “stand-in dose” iPrEP, vaginal or rectal PrEP, etc. There are various issues/concerns with PrEP such as ADRs and resistance to TDF/FTC, adherence to drugs, acceptability, sexual disinhibition, use of PrEP as first line of defense for HIV without other prevention strategies, and cost. The PrEP has a potential to address unmet need in public health if delivered as a part of comprehensive toolkit of prevention services, including risk-reduction, correct and consistent use of condoms, and diagnosis and treatment of sexually transmitted infections. PMID:21799568

The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific.

PubMed

Elmes, N J; Nasveld, P E; Kitchener, S J; Kocisko, D A; Edstein, M D

2008-11-01

Tafenoquine is being developed for radical cure and post-exposure prophylaxis of Plasmodium vivax malaria. In an open-label study, 1512 Australian Defence Force personnel received one of three tafenoquine 3 d regimens [400 mg once daily (od), 200 mg twice daily (bid), 200 mg od] or daily primaquine (22.5 mg) plus doxycycline (100 mg) over 14 d in Bougainville and in Timor-Leste for post-exposure prophylaxis. The relapse rate of subjects treated in Bougainville with tafenoquine (n=173) was 1.2% (200 mg bid x 3 d) and 2.3% (400 mg od x 3 d), while primaquine plus doxycycline (n=175) was 3.4%. For subjects treated in Timor-Leste with tafenoquine (n=636), the relapse rate was 4.9% (200 mg od x 3 d), 5.3% (200 mg bid x 3 d) and 11.0% (400 mg od x 3d), while primaquine plus doxycycline (n=289) was 10.0%. The most frequent adverse events reported across all groups were nausea, abdominal distress and diarrhoea. There was a dose-dependent reduction in adverse events with a reduced dose of tafenoquine, with the lowest dose (total 600 mg over 3 d) producing rates of adverse events equivalent to that of primaquine plus doxycycline. The much shorter dosing regimen of tafenoquine should increase compliance, which is often suboptimal with primaquine after leaving an endemic area. [Australian New Zealand Clinical Trials Registry Number 12607000588493].

To whom is HIV pre-exposure prophylaxis proposed?

PubMed

Ayerdi-Aguirrebengoa, Oskar; Vera-García, Mar; Puerta-López, Teresa; Raposo-Utrilla, Montserrat; Rodríguez-Martín, Carmen; Del Romero-Guerrero, Jorge

2017-05-01

HIV Pre-Exposure Prophylaxis (PrEP) consists of administering antiretroviral drugs to seronegative individuals with high risk practices. The aim of the study was to describe the characteristics of recent seroconverted HIV patients in order to determine the profile of the appropriate candidates for PrEP. A descriptive study of all patients diagnosed with HIV infection in 2014, and who had achieved a documented negative serology over the previous 12 months. A specific form was completed to determine the sociodemographic, behavioural, and clinical features, with complementary tests being performed for other sexually transmitted infections. Almost all (98.4%) of the 61 recent seroconverted were men who have sex with men, and aged between 20 to 39 years (88.5%). They also had a background of sexually transmitted infections (80.3%), performed multiple and unprotected sexual practices (82.7%), and under the effect of recreational drugs (87%). The evaluation of the risk factors for HIV infection in seronegative patients should enable the appropriate candidates for PrEP to be identified. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

HIV Pre-Exposure Prophylaxis and Postexposure Prophylaxis in Japan: Context of Use and Directions for Future Research and Action.

PubMed

DiStefano, Anthony S; Takeda, Makiko

2017-02-01

Biomedical HIV prevention strategies are playing an increasingly prominent role in addressing HIV epidemics globally, but little is known about their use in Japan, where persistent HIV disparities and a recently stable, but not declining, national epidemic indicate the need for evolving approaches. We conducted an ethnographic study to determine the context of pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) use and to identify directions for future research and action in Japan. We used data from observational fieldwork in the Kansai region and Tokyo Metropolitan Area (n = 178 persons observed), qualitative interviews (n = 32), documents and web-based data sources (n = 321), and email correspondences (n = 9) in the period 2013-2016. Drug approvals by Japan's regulatory agencies, insurance coverage for medications, and policies by healthcare institutions and government agencies were the main factors affecting PrEP and PEP legality, use, and awareness. Awareness and the observable presence of PrEP and PEP were very limited, particularly at the community level. PrEP and PEP held appeal for Japanese scientists and activists, and for study participants who represented various other stakeholder groups; however, significant concerns prevented open endorsements. Japanese health officials should prioritize a national discussion, weigh empirical evidence, and strongly consider formal approval of antiretroviral (ARV) medications for use in PrEP and both occupational and nonoccupational PEP. Once approved, social marketing campaigns can be used to advertise widely and increase awareness. Future research would benefit from theoretical grounding in a diffusion of innovations framework. These findings can inform current and future ARV-based prevention strategies at a critical time in the international conversation.

Evaluation of Hepatitis A Vaccine in Post-Exposure Prophylaxis, The Netherlands, 2004-2012

PubMed Central

Whelan, Jane; Sonder, Gerard J.; Bovée, Lian; Speksnijder, Arjen; van den Hoek, Anneke

2013-01-01

Background The secondary attack rate of hepatitis A virus (HAV) among contacts of cases is up to 50%. Historically, contacts were offered immunoglobulin (IG, a human derived blood product) as post-exposure prophylaxis (PEP). Amid safety concerns about IG, HAV vaccine is increasingly recommended instead. Public health authorities’ recommendations differ, particularly for healthy contacts ≥40 years old, where vaccine efficacy data is limited. We evaluated routine use of HAV vaccine as an alternative to immunoglobulin in PEP, in those considered at low risk of severe infection in the Netherlands. Methods Household contacts of acute HAV cases notified in Amsterdam (2004-2012) were invited ≤14 days post-exposure, for baseline anti-HAV testing and PEP according to national guidelines: immunoglobulin if at risk of severe infection, or hepatitis A vaccine if healthy and at low risk (aged <30, or, 30-50 years and vaccinated <8 days post-exposure). Incidence of laboratory confirmed secondary infection in susceptible contacts was assessed 4-8 weeks post-exposure. In a vaccinated subgroup, relative risk (RR) of secondary infection with estimated using Poisson regression. Results Of 547 contacts identified, 191 were susceptible to HAV. Per-protocol, 167 (87%) were vaccinated (mean:6.7 days post-exposure, standard deviation(sd)=3.3) and 24 (13%) were given immunoglobulin (mean:9.7 days post-exposure, sd=2.8). At follow-up testing, 8/112 (7%) had a laboratory confirmed infection of whom 7 were symptomatic. All secondary infections occurred in vaccinated contacts, and half were >40 years of age. In healthy contacts vaccinated per-protocol ≤8 days post-exposure, RRref. ≤15 years of secondary infection in those >40 years was 12.0 (95%CI:1.3-106.7). Conclusions Timely administration of HAV vaccine in PEP was feasible and the secondary attack rate was low in those <40 years. Internationally, upper age-limits for post-exposure vaccination vary. Pending larger studies, immunoglobulin should be considered PEP of choice in people >40 years of age and those vulnerable to severe disease. PMID:24147144

Antiretroviral Drugs in Meconium: Detection for Different Gestational Periods of Exposure.

PubMed

Himes, Sarah K; Tassiopoulos, Katherine; Yogev, Ram; Huestis, Marilyn A

2015-08-01

To determine whether antiretroviral (ARV) medications can be detected in meconium from second or third trimester, labor and delivery (L&D), or postnatal exposures. Twenty ARV medications were quantified by liquid chromatography-tandem mass spectrometry in 598 meconium samples from uninfected infants born to pregnant women with HIV enrolled in the Pediatric HIV/AIDS Cohort Study. ARV detection in meconium following third trimester exposure was 85.7%-94.4% for all ARVs except stavudine (0%, n = 2), likely because of low doses and a high limit for quantification. Of 107 samples with some second trimester only ARV exposures, meconium was positive for only lopinavir, tenofovir, or efavirenz in 11.8%-14.3% of exposed neonates; administration of these ARVs occurred between gestational weeks 25-28 in the positive samples. Days without lopinavir or tenofovir before delivery significantly correlated with decreasing concentrations of lopinavir and tenofovir in meconium. Tenofovir and lamivudine concentrations significantly correlated with increasing gestational age among infants with continuous second and third trimester exposure. Zidovudine given during L&D or for neonatal prophylaxis was detected in 95.1% and 94.6% of meconium samples, respectively. Changes in ARV treatments during pregnancy offered a unique opportunity to investigate ARV detection in meconium. ARVs in meconium primarily reflect third trimester ARV exposures, although 6 of 107 second trimester only exposures were detected. Zidovudine administration during L&D was detected in meconium indicating potential urine contamination or rapid incorporation into meconium. These data will improve interpretation of meconium drug test results. Published by Elsevier Inc.

The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors.

PubMed

Sluis-Cremer, Nicolas

2014-07-31

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance.

The Emerging Profile of Cross-Resistance among the Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors

PubMed Central

Sluis-Cremer, Nicolas

2014-01-01

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance. PMID:25089538

Animal bites and rabies exposure in Australian travellers.

PubMed

Mills, Deborah J; Lau, Colleen L; Weinstein, Philip

2011-12-19

To examine the circumstances of animal exposure in a case series of Australian travellers who required rabies postexposure prophylaxis, and to assess the appropriateness of current guidelines for rabies pre-exposure vaccination. Prospective case series of 65 returned travellers who presented to four Australian travel medicine clinics between 1 April 2009 and 31 July 2010 for rabies post-exposure prophylaxis. Demographic characteristics associated with risk of injury; countries where injuries occurred; circumstances of the injuries; and travellers' experiences of obtaining postexposure prophylaxis overseas. Animal bites and scratches occurred most commonly among travellers aged 20-29 years. Most injuries occurred in Bali, Indonesia (30 [46%]) and Thailand (21 [32%]), and the most common animals responsible for the injuries to the 65 travellers were monkeys (29 travellers [45%]) and dogs (27 [42%]). Thirty-nine of the travellers (60%) initiated contact with the animal. Forty travellers (62%) were able to commence rabies vaccination overseas, but only nine (14%) were able to obtain rabies immunoglobulin overseas. Most travellers had difficulty obtaining rabies postexposure prophylaxis overseas, resulting in significant delays in appropriate treatment. We recommend that current National Health and Medical Research Council guidelines for at-risk persons be broadened, and that the risk of rabies and the option of pre-exposure vaccination be discussed with all travellers to rabies-endemic areas.

Positive benefits: preventive impact of post-exposure prophylaxis awareness among those with diagnosed HIV.

PubMed

Dodds, C

2008-04-01

To consider the extent to which those presenting for post-exposure prophylaxis (PEP) after sexual risk had been encouraged to do so by their PEP-aware partners with (diagnosed) HIV. Thirty men who had completed the 2005 UK Gay Men's Sex Survey who said they had ever tried to get PEP took part in a 30 minute telephone interview. Fifteen men in the sample described a sexual exposure incident where they had knowledge that their partner was diagnosed with having HIV. Of these, only five knew about their partner's HIV diagnosis prior to sexual contact. The remaining 10 sought PEP because their sexual partner revealed his positive status following potential sexual exposure. Our analysis revealed that word of mouth from friends, sexual partners and health professionals played a key role in men's knowledge about the existence of PEP. It is important for HIV and sexual health specialists to ensure that PEP information is not only targeted at those who are tested negative for HIV or are untested but also to people with diagnosed HIV.

ARV-based HIV prevention for women - where we are in 2014.

PubMed

Mastro, Timothy D; Sista, Nirupama; Abdool-Karim, Quarraisha

2014-01-01

Women continue to be at special risk for HIV acquisition due to a complex mix of biological, behavioural, structural, cultural and social factors, with unacceptable rates of new infection. Scientific advances over the past decade have highlighted the use of antiretroviral (ARV) drugs as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition (sexually, parenterally and vertically) and ARV treatment (ART) for HIV-positive patients to prevent onward transmission (treatment as prevention - TasP). This paper reviews the evidence base for PrEP and TasP, describes new products in development and the need to translate research findings into programmes with impact at the population level.

Accidental exposure to biological material in healthcare workers at a university hospital: Evaluation and follow-up of 404 cases.

PubMed

Gutierrez, Eliana Battaggia; Lopes, Marta Heloísa; Yasuda, Maria Aparecida Shikanai

2005-01-01

The care and follow-up provided to healthcare workers (HCWs) from a large teaching hospital who were exposed to biological material between 1 August 1998 and 31 January 2002 is described here. After exposure, the HCW is evaluated by a nurse and doctor in an emergency consultation and receives follow-up counselling. The collection of 10 ml of blood sample from each HCW and its source patient, when known, is made for immunoenzymatic testing for HIV, HBV and HCV. Evaluation and follow-up of 404 cases revealed that the exposures were concentrated in only a few areas of the hospital; 83% of the HCWs exposed were seen by a doctor responsible for the prophylaxis up to 3 h after exposure. Blood was involved in 76.7% (309) of the exposures. The patient source of the biological material was known in 80.7% (326) of the exposed individuals studied; 80 (24.5%) sources had serological evidence of infection with 1 or more agents: 16.2% were anti-HCV positive, 3.8% were HAgBs positive and 10.9% were anti-HIV positive. 67% (273) of the study population completed the proposed follow-up. No confirmed seroconversion occurred. In conclusion, the observed adherence to the follow-up was quite low, and measures to improve it must be taken. Surprisingly, no difference in adherence to the follow-up was observed among those exposed HCW at risk, i.e. those with an infected or unknown source patient. Analysis of post-exposure management revealed excess prescription of antiretroviral drugs, vaccine and immunoglobulin. Infection by HCV is the most important risk of concern, in our hospital, in accidents with biological material.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

PubMed

Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

2017-05-09

Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Should travellers to rabies-endemic countries be pre-exposure vaccinated? An assessment of post-exposure prophylaxis and pre-exposure prophylaxis given to Danes travelling to rabies-endemic countries 2000-12.

PubMed

Christiansen, Annette H; Rodriguez, Anna B; Nielsen, Jens; Cowan, Susan A

2016-04-01

Since 2000, a steady increase of vaccines used for both rabies Post-exposure prophylaxis (PEP) and rabies Pre-exposure prophylaxis (PrEP) given to Danish travellers was observed. This study aims to evaluate whether the increase of PEP and PrEP was due to increased travelling, increased awareness of the need for PrEP, or more animal bites per travel, leading to more PEP being administered, in order to assess the need for changing the recommendations. We also described in which countries Danish travelers most frequently reported possible exposure to rabies, and evaluated the timeliness of rabies PEP, including rabies immunoglobulin (RIG). We included all Danes reported to the National Database for Rabies Treatment as having started rabies PEP either abroad or after returning to Denmark, between 2000 and 2012. Data on the yearly number of Danish travelers from 2004 to 2012 to Thailand were collected to calculate the incidence of animal bites at this destination. We also included data on rabies vaccines sold for PrEP or for booster vaccination in Denmark. PEP after possible exposure to rabies abroad increased yearly by 8.8 %. Likewise vaccines sold for PrEP increased by 8.2% annually. The number of Danish travelers to Thailand increased by 7.3% per year, resulting in a stable incidence of animal bites per 100,000 travelers. Seventy-five % started PEP in the country of exposure, while only 10 % received RIG. The yearly increase in PEP and PrEP are parallel to the yearly increase in number of travelers, and can thus be explained by the increased rate of traveling, and not by a rise in awareness of rabies risk or more bites per traveler.Even short term travelers should be given the option of including PrEP in their travel immunisation program, as PEP and especially RIG is not always available in rabies-endemic countries. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

Prescribing prophylaxis to patients who have been exposed to HIV.

PubMed

Bagley, Sue

2012-03-01

Emergency nurse practitioners should be prepared to prescribe post-exposure prophylaxis for sexual exposure (PEPSE) to people who may have been exposed to HIV, even where the number of such presentations is small. As this article makes clear, nurse prescribers require a sound knowledge of the drugs recommended in PEPSE protocols, and of their side effects, to relieve patients' anxiety and inform them about safe sexual practice. The article offers a case study and reflection to show that patients, particularly those who may have been exposed to HIV, who have been given the information they want are more likely to complete their courses of treatment.

'PrEP is not ready for our community, and our community is not ready for PrEP': pre-exposure prophylaxis for HIV for people who inject drugs and limits to the HIV prevention response.

PubMed

Guise, Andy; Albers, Eliot Ross; Strathdee, Steffanie A

2017-04-01

Pre-exposure prophylaxis for HIV, or 'PrEP', is the use of antiretroviral medicines by people who are HIV-negative to protect themselves against acquiring HIV. PrEP has shown efficacy for preventing HIV acquisition. Despite the potential, many concerns have been voiced by people who inject drugs (PWID) and their organizations. There is a need to engage with these views and ensure their integration in to policy and strategy. This paper presents PWID views on PrEP to foster the uptake of these opinions into scientific and policy debate around PrEP METHODS: Critical analysis of a report of a community consultation led by the International Network of People who Use Drugs (INPUD). The INPUD report highlights enthusiasm from PWID for PrEP, but also three main concerns: the feasibility and ethics of PrEP, its potential use as a substitute for other harm reduction strategies and how a focus on PrEP heralds a re-medicalization of HIV. Each concern relates to evidenced gaps in essential services or opposition to harm reduction and PWID human rights. People who use drugs have fundamental concerns about the potential impacts of pre-exposure prophylaxis for HIV which reflect a 'fault line' in HIV prevention: a predominance of biomedical approaches over community perspectives. Greater community engagement in HIV prevention strategy is needed, or we risk continuing to ignore the need for action on the underlying structural drivers and social context of the HIV epidemic. © 2016 Society for the Study of Addiction.

The Evaluation of Post-Exposure Prophylaxis Models for Use in the Event of an Aerosolized Anthrax Attack

DTIC Science & Technology

2014-09-01

exercise conducted in the Chicago metropolitan area revealed that the initiation of PEP on Day 5 after an attack, as opposed to on Day 2, resulted in an...Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity,” Biosecurity and Bioterrorism: Biodefense Strategy, Practice... Chicago Metropolitan Area, also concluded that the optimal cost effective response strategy is to provide antibiotic prophylaxis and vaccination for all

Factors associated with short-course antiretroviral prophylaxis (dual therapy) adherence for PMTCT in Nkangala district, South Africa.

PubMed

Peltzer, Karl; Sikwane, Elisa; Majaja, Mmapaseka

2011-09-01

To identify factors that influence adherence to short-course antiretroviral (ARV) prophylaxis by pregnant women and mothers participating in the HIV prevention of mother to child (PMTCT) programme. The sample interviewed included 139 HIV-positive antenatal women (mean gestational age 32 weeks; sexually transmitted diseases [STD] = 2.8, range 4-9 months) and 607 postnatal HIV-positive women, with either having an infant aged 1-10 weeks (30.8%), 11 weeks to 6 months (36.7%) or 7-12 months (32.5%) from Nkangala district, Mpumalanga province, South Africa. A large percentage of antenatal and postnatal women in this study initiated ARV prophylaxis for PMTCT or were on ARV (85.6% and 98%, respectively). Sixty-one per cent of antenatal and 85.9% of postnatal women reported complete adherence to the appropriate medication schedule in the 4 days preceding the interview or prior to delivery. In multivariate analysis, it was found that women with higher HIV status disclosure and less discrimination were better in maternal AZT adherence, women with higher male involvement were better in maternal and infant nevirapine adherence. Adherence to maternal and infant dual therapy prophylaxis was found to be less than optimal. Community factors (discrimination, HIV disclosure, male involvement) contribute to adherence to short-course ARV prophylaxis in this largely rural setting in South Africa. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Evolving treatment implementation among HIV-infected pregnant women and their partners: results from a national surveillance study in Italy, 2001-2015.

PubMed

Floridia, Marco; Frisina, Valentina; Ravizza, Marina; Marconi, Anna Maria; Pinnetti, Carmela; Cetin, Irene; Sansone, Matilde; Molinari, Atim; Cervi, Francesca; Meloni, Alessandra; Luzi, Kety; Masuelli, Giulia; Tamburrini, Enrica

2017-06-01

The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV-negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P  < 0.001), and in the proportion of HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P  = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV-negative partners. The results suggest good implementation of antiretroviral treatment among HIV-positive women and their HIV-positive partners, but no implementation, even in recent years, of Pre-Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.

Using serology to assist with complicated post-exposure prophylaxis for rabies and Australian bat lyssavirus.

PubMed

Conroy, Niall; Vlack, Susan; Williams, Julian M; Patten, John J; Horvath, Robert L; Lambert, Stephen B

2013-01-01

Australia uses a protocol combining human rabies immunoglobulin (HRIG) and rabies vaccine for post-exposure prophylaxis (PEP) of rabies and Australian bat lyssavirus (ABLV), with the aim of achieving an antibody titre of ≥0.5 IU/ml, as per World Health Organization (WHO) guidelines, as soon as possible. We present the course of PEP administration and serological testing for four men with complex requirements. Following dog bites in Thailand, two men (62 years old, 25 years old) received no HRIG and had delayed vaccine courses: 23 days between dose two and three, and 18 days between dose one and two, respectively. Both seroconverted following dose four. Another 62-year-old male, who was HIV-positive (normal CD4 count), also suffered a dog bite and had delayed care receiving i.m. rabies vaccine on days six and nine in Thailand. Back in Australia, he received three single and one double dose i.m. vaccines followed by another double dose of vaccine, delivered intradermally and subcutaneously, before seroconverting. A 23-year-old male with a history of allergies received simultaneous HRIG and vaccine following potential ABLV exposure, and developed rash, facial oedema and throat tingling, which was treated with a parenteral antihistamine and tapering dose of steroids. Serology showed he seroconverted following dose four. These cases show that PEP can be complicated by exposures in tourist settings where reliable prophylaxis may not be available, where treatment is delayed or deviates from World Health Organization recommendations. Due to the potentially short incubation time of rabies/ABLV, timely prophylaxis after a potential exposure is needed to ensure a prompt and adequate immune response, particularly in patients who are immune-suppressed or who have not received HRIG. Serology should be used to confirm an adequate response to PEP when treatment is delayed or where a concurrent immunosuppressing medical condition or therapy exists.

Post-exposure rabies prophylaxis in humans exposed to animals in Lublin province (Eastern Poland) in 2012–2015 – A retrospective study

PubMed Central

Krzowska-Firych, Joanna; Tomasiewicz, Krzysztof; Kozøowska, Agata

2017-01-01

ABSTRACT Rabies continues to be one of the most important viral diseases and remains a significant threat to public health across the globe. The post-exposure prophylaxis in humans can effectively prevent death after exposure to a potentially infected animal. In Poland, recommendations for rabies PEP followed the national guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures. RIG should be given for category III contact. The vaccination schedule includes 5 doses given within a 30 day period (the Essen regimen). The aim. The aim of our study was to determine the frequency of post-exposure prophylaxis among patients exposed to animals and also to assess the animal species suspected as a source of rabies exposure. Methods. We have retrospectively analyzed medical records from the years 2012–2015 of all adult patients who were exposed to animals and consulted at the Dispensary of Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. All consulted patients were asked to give an informed consent in case of decision to use collected data for future research work. Ethical approval was obtained from the Ethics Committee of the Medical University of Lublin, Poland, and all patients included in this study gave an informed consent during consultation after the exposure to animals. Results. During the studied 4-year period, 511 persons exposed to animals were consulted and prophylactic procedure consisting of active immunization were applied in 54.2% of the total consulted. Dogs and cats were the most common animal species suspected as the source of the rabies exposure. Anti-rabies prophylaxis was applied in 45.8% of all vaccinated patients exposed to dogs, and in 24.2% exposed to cats. All patients with bite wounds were consulted at the Department of Surgery and wound care followed surgical recommendations. In the study group, 45 patients had category III contact. There were 38 patients exposed to dogs, and 7 exposed to cats. There were no people exposed to wildlife in this group. All animals were available for veterinary observation. During and after exposure, none of the animals that serve as a potential source of infection presented with symptoms of rabies. The local epidemiological data indicated that during exposures of our patients, there were no confirmed cases of rabies among animals in Lublin province. Based on the data mentioned above, RIG was not applied. During the studied period in Lublin province, rabies was confirmed mainly in wildlife, and only in 2 dogs. Conclusions. In Lublin province, people are still at risk of exposure to rabid animals. The majority of our patients were vaccinated after domestic animals exposure, but rabies was confirmed mainly in wildlife, and since 2013, there were no cases of rabies among domestic animals. PMID:28166482

Post-exposure rabies prophylaxis in humans exposed to animals in Lublin province (Eastern Poland) in 2012-2015 - A retrospective study.

PubMed

Krzowska-Firych, Joanna; Tomasiewicz, Krzysztof; Kozøowska, Agata

2017-06-03

Rabies continues to be one of the most important viral diseases and remains a significant threat to public health across the globe. The post-exposure prophylaxis in humans can effectively prevent death after exposure to a potentially infected animal. In Poland, recommendations for rabies PEP followed the national guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures. RIG should be given for category III contact. The vaccination schedule includes 5 doses given within a 30 day period (the Essen regimen). The aim of our study was to determine the frequency of post-exposure prophylaxis among patients exposed to animals and also to assess the animal species suspected as a source of rabies exposure. We have retrospectively analyzed medical records from the years 2012-2015 of all adult patients who were exposed to animals and consulted at the Dispensary of Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. All consulted patients were asked to give an informed consent in case of decision to use collected data for future research work. Ethical approval was obtained from the Ethics Committee of the Medical University of Lublin, Poland, and all patients included in this study gave an informed consent during consultation after the exposure to animals. During the studied 4-year period, 511 persons exposed to animals were consulted and prophylactic procedure consisting of active immunization were applied in 54.2% of the total consulted. Dogs and cats were the most common animal species suspected as the source of the rabies exposure. Anti-rabies prophylaxis was applied in 45.8% of all vaccinated patients exposed to dogs, and in 24.2% exposed to cats. All patients with bite wounds were consulted at the Department of Surgery and wound care followed surgical recommendations. In the study group, 45 patients had category III contact. There were 38 patients exposed to dogs, and 7 exposed to cats. There were no people exposed to wildlife in this group. All animals were available for veterinary observation. During and after exposure, none of the animals that serve as a potential source of infection presented with symptoms of rabies. The local epidemiological data indicated that during exposures of our patients, there were no confirmed cases of rabies among animals in Lublin province. Based on the data mentioned above, RIG was not applied. During the studied period in Lublin province, rabies was confirmed mainly in wildlife, and only in 2 dogs. In Lublin province, people are still at risk of exposure to rabid animals. The majority of our patients were vaccinated after domestic animals exposure, but rabies was confirmed mainly in wildlife, and since 2013, there were no cases of rabies among domestic animals.

Focus on the therapeutic efficacy of 3BNC117 against HIV-1: In vitro studies, in vivo studies, clinical trials and challenges.

PubMed

Liu, Zhi-Jun; Bai, Jing; Liu, Feng-Li; Zhang, Xiang-Yang; Wang, Jing-Zhang

2017-11-01

3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo. The outcomes of Phase I and Phase IIa clinical trials in 2015 and 2016 showed the safety, tolerability, and therapeutic efficacy of 3BNC117 in HIV-1-infected human individuals. Nevertheless, anti-3BNC117 antibodies and HIV-1 strains resistant to 3BNC117 pose clinical challenges to immunotherapy with 3BNC117, so potential strategies for optimizing the potency of 3BNC117 are suggested here. Predictably, HIV-1 prevention and AIDS treatment will benefit from combinational immunotherapies with 3BNC117 and other pharmaceuticals (bNAbs, antiretroviral medicines, viral inducers, etc.) in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

Prophylaxis of Human Hydrophobia in South Korea

PubMed Central

2014-01-01

Domestic human hydrophobia has not been reported since the one case of 2004 in South Korea, but still a few animal rabies occur persistently since the reemerging stage of rabies from 1993. The government has made efforts to control animal rabies in many aspects, but whether prophylactic strategy for human hydrophobia is performed adequately is in question. The rate of proper post-exposure prophylaxis for animal bite case in 'high-risk region' of rabies is very low with 20% between 2011 and 2013. The National Animal Bite Patient Surveillance targeting 'high-risk region' is missing out animal bite cases who visit directly to hospitals in 'suspect-risk region' of rabies. Little data seems to exist for pre-exposure prophylaxis of domestic hydrophobia. Danger of reoccurrence of human hydrophobia always remain in South Korea. The medical personnel needs to have greater interest on the matter and the government strengthen the management system. PMID:25298903

Mother-to-child transmission of HIV in Kenya: results from a nationally representative study.

PubMed

Sirengo, Martin; Muthoni, Lilly; Kellogg, Timothy A; Kim, Andrea A; Katana, Abraham; Mwanyumba, Sophie; Kimanga, Davies O; Maina, William K; Muraguri, Nicolas; Elly, Benjamin; Rutherford, George W

2014-05-01

Kenya has an estimated 13,000 new infant HIV infections that occur annually. We measured the burden of HIV infection among women of childbearing age and assessed access to and coverage of key prevention of mother-to-child transmission interventions. The second Kenya AIDS Indicator Survey was a nationally representative 2-stage cluster sample of households. We analyzed data from women aged 15-54 years who had delivered a newborn within the preceding 5 years and from whom we obtained samples for HIV testing. Of 3310 women who had ≥1 live birth in the preceding 5 years, 2862 (86.5%) consented to HIV testing in the survey, and 171 (6.1%) were found to be infected. Ninety-five percent received prenatal care, 93.1% were screened for HIV during prenatal care, and of those screened, 97.8% received their test results. Seventy-six women were known to be infected in their last pregnancy. Of these, 54 (72.3%) received antepartum antiretroviral prophylaxis, and 51 (69.1%) received intrapartum prophylaxis; 56 (75.3%) reported their newborns received postpartum prophylaxis. Of the 76 children born to these mothers, 63 (82.5%) were tested for HIV at the first immunization visit or thereafter, and 8 (15.1%) were HIV infected. We found a substantial burden of HIV in Kenyan women of childbearing age and a cumulative 5-year mother-to-child transmission rate of 15%. Although screening has improved over the past 5 years, fewer than three-quarters of infected pregnant women are receiving antiretroviral prophylaxis. Universal antiretroviral therapy for HIV-infected pregnant women will be essential in achieving Kenyan's target to eliminate mother-to-child transmission to <5% by 2015.

Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana.

PubMed

Ibrahim, Maryanne; Moyo, Sikhulile; Mohammed, Terence; Mupfumi, Lucy; Gaseitsiwe, Simani; Maswabi, Kenneth; Ajibola, Gbolahan; Gelman, Rebecca; Batlang, Oganne; Sakoi, Maureen; Auletta-Young, Chloe; Makhema, Joseph; Lockman, Shahin; Shapiro, Roger L

2017-08-15

HIV point-of-care (POC) testing allows for early infant HIV diagnosis and treatment, but POC accuracy at birth and in the setting of antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission is unknown. We evaluated the Cepheid Xpert HIV-1 Qual POC test against the Roche Taqman HIV-1 DNA polymerase chain reaction (PCR) platform using dried blood spots from 15 HIV-infected and 75 HIV-exposed uninfected newborns. These infants were screened for HIV at <96 hours of life at 5 hospital maternity wards in Botswana; all infants received postexposure antiretroviral prophylaxis with single-dose nevirapine and zidovudine, and most mothers received 3-drug antiretroviral therapy in pregnancy and at delivery. Fourteen of the 15 PCR positive samples tested positive by Cepheid POC, yielding a sensitivity of 93.3% (95% confidence interval: 68.1 to 99.8). Baseline viral load among positive infants ranged from <40 to >10,000,000 copies/mL, with a median of 2403 copies/mL. The HIV RNA for the infant with false-negative POC testing was 1661 copies/mL. Of note, 2 infants with low HIV RNA (<40 and 272 copies/mL) were correctly identified as HIV positive by Cepheid POC. All the 75 PCR-negative samples tested negative by Cepheid POC, yielding a specificity of 100% (95% confidence interval: 96.1 to 100). Our study demonstrates high sensitivity and specificity for the Cepheid POC assay in the first week of life despite early infection and antiretroviral prophylaxis. This platform may be a useful approach for adding early infant HIV diagnosis to current testing programs.

'On December 1, 2015, sex changes. Forever': Pre-exposure prophylaxis and the pharmaceuticalisation of the neoliberal sexual subject.

PubMed

Thomann, Matthew

2018-08-01

The global scale-up of AIDS treatment initiatives during the first decade of the twenty-first century has been referred to as a kind of 'pharmaceuticalisation' of public health, a trend that is now building in the area of HIV prevention. This paper traces the emergence and increased uptake of pre-exposure prophylaxis (PrEP), antiretroviral medications that can keep HIV negative individuals from becoming infected, placing it within the broader (re)casting of HIV prevention as a medical and technological problem that has been central to the recent 'end of AIDS' discourse. While HIV prevention discourses have been grounded in a neoliberal calculus of individual responsibility since the late 1990s, PrEP constitutes a pharmaceutical extension of the responsibilised sexual subject. Central to this extension are the acknowledgment of one's risk and a willingness to take pre-emptive medical action to secure a future without HIV. For men who have sex with men, a population heavily targeted for biomedical interventions in the United States, PrEP marks a shift in moral discourses of what it means to be a responsible sexual subject. Characteristics of the pharmaceutical extension of the neoliberal sexual subject are explored through an examination of a New York City-based PrEP promotional campaign.

Negotiating sexual safety in the era of biomedical HIV prevention: relationship dynamics among male couples using pre-exposure prophylaxis.

PubMed

Malone, Jowanna; Syvertsen, Jennifer L; Johnson, Blake E; Mimiaga, Matthew J; Mayer, Kenneth H; Bazzi, Angela R

2018-06-01

Up to two-thirds of new cases of HIV transmission between gay, bisexual and other men who have sex with men in the USA are attributed to primary relationships. Understanding the relationship dynamics and sexual agreements of male-male couples can provide insight into HIV transmission patterns and prevention needs in this population. The daily use of antiretroviral pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, but its negotiation and use within social and intimate relationship contexts remain understudied. We conducted semi-structured qualitative interviews with 20 male couples (n = 40 men) in which at least one partner was either using or in the process of initiating PrEP. Congruent with a theoretical focus on social theories of relationships and negotiated risk, couples were interviewed about relationship dynamics, trust, communication and sexual health practices, including their perception and use of PrEP. Overall, we found that couples showed heightened trust and communication when establishing open, sexual agreements and demonstrated high awareness of sexual risks and health practices in the context of PrEP use. This study demonstrates how understanding relationship dynamics can better inform HIV prevention and sexual health promotion efforts for male couples at risk of HIV.

What is the place of pre-exposure prophylaxis in HIV prevention?

PubMed

De Man, Jeroen; Colebunders, Robert; Florence, Eric; Laga, Marie; Kenyon, Christopher

2013-01-01

New tools are needed to bring down ongoing high HIV incidence. This review aims to evaluate the place of one of these new tools (pre-exposure prophylaxis) in a comprehensive prevention strategy. Several trials have demonstrated the safety and the efficacy of pre-exposure prophylaxis in HIV prevention. Two large trials have, however, failed to show such efficacy. This was likely due to poor adherence in these trials. New forms of long-acting pre-exposure prophylaxis currently in trials may deal with these problems of low adherence. Pre-exposure prophylaxis has been demonstrated to be cost-effective within certain settings. The introduction of pre-exposure prophylaxis into prevention programs needs to be carefully thought through. For example, pre-exposure prophylaxis-induced risk compensation, at both an individual and population level, could undermine other aspects of a comprehensive HIV prevention program. In conclusion, pre-exposure prophylaxis could be a useful additional tool for the prevention of HIV in specific high-risk groups. It should be implemented in a way that deals with issues such as ensuring high adherence and ensuring that pre-exposure prophylaxis does not detract from, but complements, other more fundamental elements of HIV prevention programs.

Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment

PubMed Central

Cooper, Jason D.; Tomasik, Jakub; Bahn, Sabine; Aerts, Joeri L.; Osterhaus, Albert D. M. E.; Gruters, Rob A.; Andeweg, Arno C.

2018-01-01

Objectives To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. Design An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. Methods Plasma marker (‘analyte’) levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. Results Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. Conclusions Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection. PMID:29389978

Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment.

PubMed

van den Ham, Henk-Jan; Cooper, Jason D; Tomasik, Jakub; Bahn, Sabine; Aerts, Joeri L; Osterhaus, Albert D M E; Gruters, Rob A; Andeweg, Arno C

2018-01-01

To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. Plasma marker ('analyte') levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection.

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries

PubMed Central

2013-01-01

Background Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. Methods Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12–24 months after delivery (n = 1070). Women with a CD4 count of 200-500cells/mm3 and gestational age 28–36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm3 initiated antiretroviral therapy, and >500 cells/mm3 received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. Results At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1–2 months of ARV’s, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. Conclusions Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring. Trial registration number ISRCTN71468401 PMID:24192332

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries.

PubMed

Sartorius, Benn K D; Chersich, Matthew F; Mwaura, Mary; Meda, Nicolas; Temmerman, Marleen; Newell, Marie Louise; Farley, Timothy M M; Luchters, Stanley

2013-11-06

Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12-24 months after delivery (n = 1070). Women with a CD4 count of 200-500 cells/mm(3) and gestational age 28-36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm(3) initiated antiretroviral therapy, and >500 cells/mm(3) received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥ 6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1-2 months of ARV's, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring. ISRCTN71468401.

Safety of Perinatal Exposure to Antiretroviral Medications: Developmental Outcomes in Infants

PubMed Central

Sirois, Patricia A.; Huo, Yanling; Williams, Paige L.; Malee, Kathleen; Garvie, Patricia A.; Kammerer, Betsy; Rich, Kenneth; Van Dyke, Russell B.; Nozyce, Molly L.

2013-01-01

Background This study evaluated effects of perinatal exposure to antiretroviral (ARV) medications on neurodevelopment of HIV-exposed, uninfected infants. Methods HIV-exposed, uninfected infants (age 9-15 months) enrolled in SMARTT, a multisite prospective surveillance study, completed the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III), assessing cognition, language, motor skills, social-emotional development, and adaptive behavior. Linear regression models were used to evaluate associations between Bayley-III outcomes in infants with and without perinatal and neonatal ARV exposure, by regimen (combination ARV [cARV] versus non-cARV), type of regimen (defined by drug class), and individual ARVs (for infants with cARV exposure), adjusting for maternal and infant health and demographic covariates. Results As of May 2010, 374 infants had valid Bayley-III evaluations. Median age at testing was 12.7 months; 49% male, 79% black, 16% Hispanic. Seventy-nine percent were exposed to regimens containing protease inhibitors (PIs; 9% of PI-containing regimens also included non-nucleoside reverse transcriptase inhibitors [NNRTIs]), 5% to regimens containing NNRTIs (without PI), and 14% to regimens containing only nucleoside reverse transcriptase inhibitors (NRTIs). Overall, 83% were exposed to cARV. No Bayley-III outcome was significantly associated with overall exposure to cARV, ARV regimen, or neonatal prophylaxis. For individual ARVs, following sensitivity analyses, the adjusted group mean on the Language domain was within age expectations but significantly lower for infants with perinatal exposure to atazanavir (p=0.01). Conclusions These results support the safety of perinatal ARV use. Continued monitoring for adverse neurodevelopmental outcomes in older children is warranted, and the safety of atazanavir merits further study. PMID:23340561

Do Australian immunoglobulin products meet international measles antibody titer standards?

PubMed

Young, Megan K; Bertolini, Joseph; Kotharu, Pushpa; Maher, Darryl; Cripps, Allan W

2017-03-04

The effectiveness of passive immunisation post-exposure to measles appears subject to a dose-response effect. New Zealand and the United Kingdom have increased the recommended dose of polyclonal human immunoglobulin for post-exposure prophylaxis within the last decade in response to concerns about decreasing levels of measles antibodies in these products. This study used the plaque-reduction neutralization test (PRNT) to measure the titer of measles-specific antibodies in Australian immunoglobulin products for post-exposure prophylaxis and compared the utility of an enzyme-linked immunosorbent assay (ELISA) to the PRNT in available Australian and international samples: Australian intramuscular (n = 10), Australian intravenous (n = 28), New Zealand intramuscular (n = 2), Hizentra (subcutaneous)(USA) (n = 3), and Privigen (intravenous)(USA) (n = 2). Measles titres in Australian IM and IV immunoglobulins ranged from 51 to 76 IU/mL and 6 to 24 IU/mL respectively, as measured by PRNT calibrated to the WHO 3 rd international standard. ELISA titres were variable but higher than PRNT titres in all tested samples. Measles antibody titres in Australian immunoglobulin products meet consensus-prescribed international thresholds. Development of a convenient, standardized, readily accessible assay for determination of measles titres in immunoglobulin products would be useful for future studies and facilitate international comparisons.

Assessment of the Impact of Cotrimoxazole Prophylaxis on Key Outcomes Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review

PubMed Central

Hassani, Ahmed Saadani; Marston, Barbara J.; Kaplan, Jonathan E.

2016-01-01

Background Cotrimoxazole (CTX) prophylaxis is among the key interventions provided to HIV-infected individuals in resource-limited settings. We conducted a systematic review of the available evidence. Methods MEDLINE, Embase, Global Health, CINAHL, SOCA, and African Index Medicus (AIM) were used to identify articles relevant to the CTX prophylaxis intervention from 1995 to 2014. Included articles addressed impact of CTX prophylaxis on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated the quality of evidence in individual articles and assessed the overall quality of the body of evidence, the expected impact, and the cost effectiveness (CE) for each outcome. Results Of the initial 1418 identified articles, 42 met all inclusion criteria. These included 9 randomized controlled trials, 26 observational studies, 2 systematic reviews with meta-analysis, 1 other systematic review, and 4 CE studies. The overall quality of evidence was rated as “good” and the expected impact “high” for both mortality and morbidity. The overall quality of evidence from the 4 studies addressing retention in care was rated as “poor,” and the expected impact on retention was rated as “uncertain.” The 4 assessed CE studies showed that provision of CTX prophylaxis is cost effective and sometimes cost saving. No studies addressed impact on quality of life or HIV transmission. Conclusions CTX prophylaxis is a cost-effective intervention with expected high impact on morbidity and mortality reduction in HIV-infected adults in resource-limited settings. Benefits are seen in both pre-antiretroviral therapy and antiretroviral therapy populations. PMID:25768865

Pre-exposure rabies prophylaxis: a systematic review.

PubMed

Kessels, Jocelyn A; Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

2017-03-01

To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings. We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

Pre-exposure rabies prophylaxis: a systematic review

PubMed Central

Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

2017-01-01

Abstract Objective To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings. Methods We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Findings Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Conclusion Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities. PMID:28250534

Household exposure and animal-bite surveillance following human rabies detection in Southern Ghana.

PubMed

Afakye, Kofi; Kenu, Ernest; Nyarko, Kofi Mensah; Johnson, Sherry Ama Mawuko; Wongnaah, Florence; Bonsu, George Kwame

2016-01-01

Rabies remains a neglected tropical zoonotic disease with 100% case fatality rate and estimated 6,000 global mortality annually, and yet vaccine preventable. In Ghana, rabies outbreaks receive poor response. We investigated rabies in a 5-year old boy to find the source of infection, identify exposed persons for post-exposure prophylaxis and describe animal-bite surveillance in Manya-Krobo District of Ghana. We actively searched for cases and exposures by interviewing household members of the victim, schoolmates, and health professionals using WHO case definition, interview guide and checklist. We reviewed health and veterinary records and reports, and interviewed stakeholders. Descriptive data analyses were carried out and presented using tables and charts. Recorded responses were transcribed into thematic areas and analysed. Child had dog-bite at the wrist, and developed hyperactivity, hydrophobia and hyperventilation 2 months post bite. He was hospitalised and died from respiratory failure day 3 after admission. Thirty-three persons were exposed to rabies infectious material. Females were 66%, age-groups 5-15yrs and 30-59 yrs were 33.3% and 39.4% respectively. A third (11/33) were category II exposure by WHO classification and were recommended for post-exposure prophylaxis. Surveillance records showed ninety-two animal-bite cases were reported for past 12 months. Half were females, and 18-59yrs age-group was 43%. Surveillance data quality was poor. Rabies remains a public health burden inGhana with domestic dog as reservoir of the virus and females more vulnerable to secondary exposures. Health education on rabies should be intensified, and robust animal-bite surveillance system put in place.

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation.

PubMed

Cambiano, Valentina; Miners, Alec; Dunn, David; McCormack, Sheena; Ong, Koh Jun; Gill, O Noel; Nardone, Anthony; Desai, Monica; Field, Nigel; Hart, Graham; Delpech, Valerie; Cairns, Gus; Rodger, Alison; Phillips, Andrew N

2018-01-01

In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain. In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs. Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex. This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised. National Institute for Health Research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Polarised press reporting about HIV prevention: Social representations of pre-exposure prophylaxis in the UK press.

PubMed

Jaspal, Rusi; Nerlich, Brigitte

2017-09-01

Pre-exposure prophylaxis is a novel biomedical HIV prevention option for individuals at high risk of HIV acquisition. Although pre-exposure prophylaxis has yielded encouraging results in various clinical trials, opponents argue that pre-exposure prophylaxis poses a number of risks to human health and to sexually transmitted infection prevention efforts. Using qualitative thematic analysis and social representation theory, this article explores coverage of pre-exposure prophylaxis in the UK print media between 2008 and 2015 in order to chart the emerging social representations of this novel HIV prevention strategy. The analysis revealed two competing social representations of pre-exposure prophylaxis: (1) as a positive development in the 'battle' against HIV (the hope representation) and (2) as a medical, social and psychological setback in this battle, particularly for gay/bisexual men (the risk representation). These social representations map onto the themes of pre-exposure prophylaxis as a superlatively positive development; pre-exposure prophylaxis as a weapon in the battle against HIV/AIDS; and risk, uncertainty and fear in relation to pre-exposure prophylaxis. The hope representation focuses on taking (individual and collective) responsibility, while the risk representation focuses on attributing (individual and collective) blame. The implications for policy and practice are discussed.

Post-exposure Prophylaxis Awareness, Knowledge, Access and Use Among Three Populations in New York City, 2016-17.

PubMed

Koblin, Beryl A; Usher, DaShawn; Nandi, Vijay; Tieu, Hong-Van; Bravo, Eddie; Lucy, Debbie; Miles, London; Ortiz, Geneva; Kindlon, Marcia J; Parisi, Donna M; Frye, Victoria

2018-06-01

Post-exposure prophylaxis (PEP) is a cost-effective, but underused HIV prevention strategy. PEP awareness, knowledge, access, and usage was assessed among young men of color who have sex with men (YMSMOC; n = 177), transgender women (TW; n = 182), and cisgender women of color (CWOC; n = 170) in New York City. 59% were aware of PEP: 80% among YMSMOC, 63% among TW and 34% among CWOC (p < 0.001). 13% had ever used PEP. PEP awareness was higher among YMSMOC with a recent HIV test and lower among those with ≥ 4 partners. PEP awareness was lower among TW who anticipated stigma and reported barriers to taking PEP, and higher among TW who exchanged sex for resources. Among CWOC, more barriers to taking PEP reduced the odds of PEP awareness. PEP education and outreach needs to be deliberate about population-specific campaigns, with a need to focus on reducing PEP stigma and other barriers which impede PEP access.

Measures against transmission of pandemic H1N1 influenza in Japan in 2009: simulation model.

PubMed

Yasuda, H; Suzuki, K

2009-11-05

The first outbreak of pandemic H1N1 influenza in Japan was contained in the Kansai region in May 2009 by social distancing measures. Modelling methods are needed to estimate the validity of these measures before their implementation on a large scale. We estimated the transmission coefficient from outbreaks of pandemic H1N1 influenza among school children in Japan in summer 2009; using this transmission coefficient, we simulated the spread of pandemic H1N1 influenza in a virtual community called the virtual Chuo Line which models an area to the west of metropolitan Tokyo. Measures evaluated in our simulation included: isolation at home, school closure, post-exposure prophylaxis and mass vaccinations of school children. We showed that post-exposure prophylaxis combined with isolation at home and school closure significantly decreases the total number of cases in the community and can mitigate the spread of pandemic H1N1 influenza, even when there is a delay in the availability of vaccine.

Simultaneous Measurement of Etravirine, Maraviroc and Raltegravir in Pigtail Macaque Plasma, Vaginal Secretions and Vaginal Tissue using a LC-MS/MS Assay

PubMed Central

Blakney, Anna K.; Jiang, Yonghou; Whittington, Dale; Woodrow, Kim A.

2016-01-01

Etravirine (ETR), maraviroc (MVC) and raltegravir (RAL) are promising antiretroviral drugs being used in HIV treatment and may be interesting for prevention applications such as oral or topical pre-exposure prophylaxis. Here we describe a sensitive and accurate method for the simultaneous detection of ETR, MVC and RAL from pigtail macaque plasma, vaginal secretions, and vaginal tissue. This method is characterized by a straightforward precipitation extraction method, a limit of quantification <0.5 ng mL−1 for all three antiretrovirals bolstered by a corresponding internal standard for each drug analyte, and short run time. Quantification is performed using positive ion electrospray triple quadrupole mass spectrometry. This method was validated over clinically relevant ranges for the three ARV drugs in all three matrices: 0.1–100 ng mL−1 for ETR, 0.05–100 ng mL−1 for MVC and 1–100 ng mL−1 for RAL. Our method is accurate and precise, with measured mean inter-assay precision (%CV) and accuracy (% bias) of 5.08% and 1.96%, respectively, while the mean intra-assay precision and accuracy were 3.44% and 1.08 %. The overall post-extraction recovery for ETR, MVC and RAL was >94% in all cases. We also show that extracted biological samples are stable after storage at room temperature or 4 °C and after three freeze/thaw cycles. This is the first analytical method capable of quantifying ETR, MVC and RAL in biological matrices relevant for pre-clinical testing of oral or topical HIV prevention methods in pigtailed macaques. PMID:27236000

Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women.

PubMed

Mugwanya, Kenneth K; John-Stewart, Grace; Baeten, Jared

2017-07-01

In settings where HIV is prevalent in heterosexual populations, pregnancy and postpartum breastfeeding periods can be associated with substantial HIV acquisition risk. Pre-exposure prophylaxis (PrEP) with daily oral tenofovir disoproxil fumarate (TDF)/emtricitabine is an attractive HIV prevention option for women who are lactating but data are limited on its safety during the lactation period. Areas covered: We provide a concise synthesis and summary of current evidence on the safety of TDF-based PrEP during breastfeeding. We conducted a review, searching Pubmed database and major PrEP conferences for primary studies with TDF-based PrEP exposure during postpartum breastfeeding. Expert opinion: TDF-based oral PrEP is an effective female-controlled HIV prevention option. There is evidence supporting the safety of TDF use for infant outcomes during breastfeeding in antiretroviral treatment regimens for HIV and hepatitis B virus, and more limited, but consistently safe, data from use of TDF as PrEP. The potential for risk is arguably outweighed for at-risk individuals by HIV prevention benefits, including indirect protection to the infant as a result of preventing HIV in the breastfeeding mother. As PrEP delivery is scaled up in heterosexual populations in high HIV prevalence settings and for at-risk persons in other settings, implementation science studies can provide a framework to increase the accrual of safety, acceptability, and use data related to PrEP during lactation.

Cell Phone-Based and Adherence Device Technologies for HIV Care and Treatment in Resource-Limited Settings: Recent Advances.

PubMed

Campbell, Jeffrey I; Haberer, Jessica E

2015-12-01

Numerous cell phone-based and adherence monitoring technologies have been developed to address barriers to effective HIV prevention, testing, and treatment. Because most people living with HIV and AIDS reside in resource-limited settings (RLS), it is important to understand the development and use of these technologies in RLS. Recent research on cell phone-based technologies has focused on HIV education, linkage to and retention in care, disease tracking, and antiretroviral therapy adherence reminders. Advances in adherence devices have focused on real-time adherence monitors, which have been used for both antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has recently been combined with cell phone-based technologies to create real-time adherence interventions using short message service (SMS). New developments in adherence technologies are exploring ingestion monitoring and metabolite detection to confirm adherence. This article provides an overview of recent advances in these two families of technologies and includes research on their acceptability and cost-effectiveness when available. It additionally outlines key challenges and needed research as use of these technologies continues to expand and evolve.

"I never thought that it would happen … " Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya.

PubMed

Ngure, Kenneth; Vusha, Sophie; Mugo, Nelly; Emmanuel-Fabula, Mira; Ngutu, Mariah; Celum, Connie; Baeten, Jared M; Heffron, Renee

2016-12-01

In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples' needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples' communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples' counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.

Prophylaxis and treatment of HIV-1 infection in pregnancy - Swedish Recommendations 2017.

PubMed

Navér, Lars; Albert, Jan; Carlander, Christina; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Svedhem-Johansson, Veronica; Sönnerborg, Anders; Westling, Katarina; Yilmaz, Aylin; Pettersson, Karin

2018-01-24

Prophylaxis and treatment with antiretroviral drugs have resulted in a very low rate of mother-to-child transmission (MTCT) of HIV during recent years. Registration of new antiretroviral drugs, modification of clinical praxis, updated general treatment guidelines and increasing knowledge about MTCT have necessitated regular revisions of the recommendations for 'Prophylaxis and treatment of HIV-1 infection in pregnancy'. The Swedish Reference Group for Antiviral Therapy (RAV) has updated the recommendations from 2013 at an expert meeting 19 September 2017. In the new text, current treatment guidelines for non-pregnant are considered. The most important revisions are that: (1) Caesarean section and infant prophylaxis with three drugs are recommended when maternal HIV RNA >150 copies/mL (previously >50 copies/mL). The treatment target of undetectable HIV RNA remains unchanged <50 copies/mL; (2) Obstetric management and mode of delivery at premature rupture of the membranes and rupture of the membranes at full term follow the same procedures as in HIV negative women; (3) Vaginal delivery is recommended to a well-treated woman with HIV RNA <150 copies/mL regardless of gestational age, if no obstetric contraindications are present; (4) Treatment during pregnancy should begin as soon as possible and should continue after delivery; (5) Ongoing well-functioning HIV treatment at pregnancy start should usually be retained; (6) Recommended drugs and drug combinations have been updated.

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

PubMed

Baeten, Jared M; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R; Campbell, James D; Wangisi, Jonathan; Tappero, Jordan W; Bukusi, Elizabeth A; Cohen, Craig R; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kakia, Aloysious; Odoyo, Josephine; Mucunguzi, Akasiima; Nakku-Joloba, Edith; Twesigye, Rogers; Ngure, Kenneth; Apaka, Cosmas; Tamooh, Harrison; Gabona, Fridah; Mujugira, Andrew; Panteleeff, Dana; Thomas, Katherine K; Kidoguchi, Lara; Krows, Meighan; Revall, Jennifer; Morrison, Susan; Haugen, Harald; Emmanuel-Ogier, Mira; Ondrejcek, Lisa; Coombs, Robert W; Frenkel, Lisa; Hendrix, Craig; Bumpus, Namandjé N; Bangsberg, David; Haberer, Jessica E; Stevens, Wendy S; Lingappa, Jairam R; Celum, Connie

2012-08-02

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

PubMed

Manning, Susan E; Rupprecht, Charles E; Fishbein, Daniel; Hanlon, Cathleen A; Lumlertdacha, Boonlert; Guerra, Marta; Meltzer, Martin I; Dhankhar, Praveen; Vaidya, Sagar A; Jenkins, Suzanne R; Sun, Benjamin; Hull, Harry F

2008-05-23

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.

[Childhood tuberculosis].

PubMed

Hamzaoui, A

2015-01-01

Childhood TB is an indication of failing TB control in the community. It allows disease persistence in the population. Mortality and morbidity due to TB is high in children. Moreover, HIV co-infection and multidrug-resistant diseases are as frequent in children as in adults. Infection is more frequent in younger children. Disease risk after primary infection is greatest in infants younger than 2 years. In case of exposure, evidence of infection can be obtained using the tuberculin skin test (TST) or an interferon-gamma assay (IGRA). There is no evidence to support the use of IGRA over TST in young children. TB suspicion should be confirmed whenever possible, using new available tools, particularly in case of pulmonary and lymph node TB. Induced sputum, nasopharyngeal aspiration and fine needle aspiration biopsy provide a rapid and definitive diagnosis of mycobacterial infection in a large proportion of patients. Analysis of paediatric samples revealed higher sensitivity and specificity values of molecular techniques in comparison with the ones originated from adults. Children require higher drugs dosages than adults. Short courses of steroids are associated with TB treatment in case of respiratory distress, bronchoscopic desobstruction is proposed for severe airways involvement and antiretroviral therapy is mandatory in case of HIV infection. Post-exposure prophylaxis in children is a highly effective strategy to reduce the risk of TB disease. The optimal therapy for treatment of latent infection with a presumably multidrug-resistant Mycobacterium tuberculosis strain is currently not known. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Haematological features in children less than 12 years on cotrimoxazole prophylaxis seen in opportunistic infection clinics at Harare and Parirenyatwa Teaching Hospitals.

PubMed

Mateveke-Kuona, P; Bwakura, M F; Dzangare, J; Pazvakavambwa, I

2010-01-01

To determine the prevalence of peripheral haematological abnormalities in children receiving cotrimoxazole prophylaxis. An outpatient hospital based cross sectional study. The study was conducted at two tertiary peadiatric HIV clinics that offer comprehensive care to children living with HIV. 202 HIV infected, antiretroviral therapy naive children aged between 3 months and 12 years who were receiving cotrimoxazole prophylaxis for at least 1 month with more than95% adherence to prophylaxis were included. Haematological abnormalities on full blood count and peripheral film. The prevalence of anaemia was 62% with normocytic normochromic anaemia being the most frequent type (45%). The commonest red blood cell abnormality was rouleaux formation on the peripheral film. Monocytosis occurred in 62%, leucopaenia in 39%, eosinophilia in 34%, neutropaenia in 18% and lymphopaenia in 10% of the children. This study showed a high prevalence ofhaematological abnormalities in HIV infected children on cotrimoxazole prophylaxis. It emphasizes the need for evaluation for anaemia and its management in children on cotrimoxazole prophylaxis.

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

PubMed

Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits observed in clinical trials are maintained in real-world use.

Willingness to Self-Pay for Pre-exposure Prophylaxis in Men Who Have Sex With Men: A National Online Survey in Taiwan.

PubMed

Ko, Nai-Ying; Chen, Bo-Jie; Li, Chia-Wen; Ku, Wen-Wei; Hsu, Su-Ting

2016-04-01

High cost of pre-exposure prophylaxis (PrEP) is a major concern for acceptability. This study determined the willingness of men who have sex with men to self-pay for PrEP and factors associated with the likelihood of condom use if taking PrEP. The Taiwan 2014 MSM Online Sex Survey was conducted and data such as demographics, attitudes toward PrEP, and sexual behaviors in the previous 3 months were collected. Of the 1,151 MSM who participated, 56% were willing to take PrEP, but only 23% were willing to self-pay $340 for PrEP. Willingness to self-pay for PrEP was significantly associated with the previous receipt of nonoccupational post-exposure prophylaxis (adjusted odds ratio [AOR], 3.02, 95%CI [1.49, 6.12]), and positive attitudes toward PrEP (AOR, 3.02, 95%CI [2.19, 4.17]). Of MSM who are willing to use PrEP, 73.6% would maintain condom use if taking PrEP. If PrEP is made available in Taiwan, more efforts should be focused on increasing awareness of MSM who are practicing risky behaviors.

Use of HIV PEPSE and Hepatitis B vaccine following the introduction of a SARC.

PubMed

Bennett, Judy; Johnson, Sandie

2011-11-01

Adherence to local guidelines on the use of HIV post exposure prophylaxis (PEP) and hepatitis B vaccine following sexual assault was evaluated by means of audit. Forensic Medical Examiners (FMEs) were asked to complete an audit form after conducting sexual offence examinations at Gloucester Sexual Assault Referral Centre (SARC). Only one HIV PEP pack was prescribed during the six and a half month audit period. Examination of the SARC records of the allegations made by complainants did not reveal any high-risk cases involving a failure to offer HIV post-exposure prophylaxis following sexual exposure (PEPSE). The majority of the examinations performed at the SARC were carried out by trained sexual offence examiners (SOEs). The audit indicates that these SOEs were considering the appropriate use of HIV PEPSE and hepatitis B vaccine when they performed examinations. Some examinations were performed by general forensic medical examiners who completed the audit forms infrequently. It was not possible to determine whether these examiners were considering the appropriate use of HIV PEPSE and hepatitis treatments. Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... vaccines for a post-exposure prophylaxis indication using the animal rule. On November 17, 2010, the...

Oral Pre-Exposure Prophylaxis (PrEP) for Prevention of HIV in Serodiscordant Heterosexual Couples in the United States: Opportunities and Challenges

PubMed Central

Myers, Julie E.; Kurth, Ann E.; Cohen, Stephanie E.; Mannheimer, Sharon B.; Simmons, Janie; Pouget, Enrique R.; Trabold, Nicole; Haberer, Jessica E.

2014-01-01

Abstract Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention approach in which HIV-negative individuals are provided with daily oral antiretroviral medication for the primary prevention of HIV-1. Several clinical trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at high risk for HIV, with adherence closely associated with level of risk reduction. In the United States (US), three groups have been prioritized for initial implementation of PrEP—injection drug users, men who have sex with men at substantial risk for HIV, and HIV-negative partners within serodiscordant heterosexual couples. Numerous demonstration projects involving PrEP implementation among MSM are underway, but relatively little research has been devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples in the US. Such couples face a unique set of challenges to PrEP implementation at the individual, couple, and provider level with regard to PrEP uptake and maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk behavior. Oral PrEP also provides new opportunities for serodiscordant couples and healthcare providers for primary prevention and reproductive health. This article provides a review of the critical issues, challenges, and opportunities involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual couples in the US. PMID:25045996

Optimizing content for pre-exposure prophylaxis (PrEP) counseling for men who have sex with men: Perspectives of PrEP users and high-risk PrEP naïve men.

PubMed

Wade Taylor, S; Mayer, Kenneth H; Elsesser, Steven M; Mimiaga, Matthew J; O'Cleirigh, Conall; Safren, Steven A

2014-05-01

Existing trials of antiretroviral (ARV) medication as chemoprophylaxis against HIV reveal that the degree of protection is primarily dependent on product adherence. However, there is a lack of data on targets for behavioral interventions to improve adherence to ARV as prevention. Information from individuals who have used ARV as pre-exposure prophylaxis (PrEP) can inform behavioral intervention development. Thirty-nine HIV-uninfected MSM at high risk for HIV acquisition participated in one of four semi-structured focus groups. Two of the focus groups consisted of MSM who had been prescribed and used PrEP in the context of a clinical trial; the other two consisted of high-risk MSM who had not previously used PrEP. An in-depth, within-case/across-case content analysis resulted in six descriptive themes potentially salient for a PrEP adherence behavioral intervention: (1) motivations to use PrEP, (2) barriers to PrEP use, (3) facilitators to PrEP use, (4) sexual decision-making in the context of PrEP, (5) prospective PrEP education content, and, (6) perceived effective characteristics of PrEP delivery personnel. Addressing these themes in behavioral interventions in the context of prescribing PrEP may result in the optimal "packaging" public health programs that implement PrEP for high-risk MSM.

Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus-Independent Administration Efficiently Prevent HIV Transmission

PubMed Central

Date, Abhijit A.; Long, Julie M.; Nochii, Tomonori; Belshan, Michael; Shibata, Annemarie; Vincent, Heather; Baker, Caroline E.; Thayer, William O.; Kraus, Guenter; Lachaud-Durand, Sophie; Williams, Peter; Destache, Christopher J.; Garcia, J. Victor

2015-01-01

Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent HIV transmission are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations of the reverse transcriptase inhibitor rilpivirine for pericoital and coitus-independent HIV prevention. Topically applied rilpivirine, encapsulated in PLGA nanoparticles, was delivered in a thermosensitive gel, which becomes solid at body temperature. PLGA nanoparticles with encapsulated rilpivirine coated the reproductive tract and offered significant protection to BLT humanized mice from a vaginal high-dose HIV-1 challenge. A different nanosuspension of crystalline rilpivirine (RPV LA), administered intramuscularly, protected BLT mice from a single vaginal high-dose HIV-1 challenge one week after drug administration. Using transmitted/founder viruses, which were previously shown to establish de novo infection in humans, we demonstrated that RPV LA offers significant protection from two consecutive high-dose HIV-1 challenges one and four weeks after drug administration. In this experiment, we also showed that, in certain cases, even in the presence of drug, HIV infection could occur without overt or detectable systemic replication until levels of drug were reduced. We also showed that infection in the presence of drug can result in acquisition of multiple viruses after subsequent exposures. These observations have important implications for the implementation of long-acting antiretroviral formulations for HIV prevention. They provide first evidence that occult infections can occur, despite the presence of sustained levels of antiretroviral drugs. Together, our results demonstrate that topically- or systemically administered rilpivirine offers significant coitus-dependent or coitus-independent protection from HIV infection. PMID:26271040

Household exposure and animal-bite surveillance following human rabies detection in Southern Ghana

PubMed Central

Afakye, Kofi; Kenu, Ernest; Nyarko, Kofi Mensah; Johnson, Sherry Ama Mawuko; Wongnaah, Florence; Bonsu, George Kwame

2016-01-01

Introduction Rabies remains a neglected tropical zoonotic disease with 100% case fatality rate and estimated 6,000 global mortality annually, and yet vaccine preventable. In Ghana, rabies outbreaks receive poor response. We investigated rabies in a 5-year old boy to find the source of infection, identify exposed persons for post-exposure prophylaxis and describe animal-bite surveillance in Manya-Krobo District of Ghana. Methods We actively searched for cases and exposures by interviewing household members of the victim, schoolmates, and health professionals using WHO case definition, interview guide and checklist. We reviewed health and veterinary records and reports, and interviewed stakeholders. Descriptive data analyses were carried out and presented using tables and charts. Recorded responses were transcribed into thematic areas and analysed. Results Child had dog-bite at the wrist, and developed hyperactivity, hydrophobia and hyperventilation 2 months post bite. He was hospitalised and died from respiratory failure day 3 after admission. Thirty-three persons were exposed to rabies infectious material. Females were 66%, age-groups 5-15yrs and 30-59 yrs were 33.3% and 39.4% respectively. A third (11/33) were category II exposure by WHO classification and were recommended for post-exposure prophylaxis. Surveillance records showed ninety-two animal-bite cases were reported for past 12 months. Half were females, and 18-59yrs age-group was 43%. Surveillance data quality was poor. Conclusion Rabies remains a public health burden inGhana with domestic dog as reservoir of the virus and females more vulnerable to secondary exposures. Health education on rabies should be intensified, and robust animal-bite surveillance system put in place. PMID:28149437

Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery.

PubMed

Hu, Minlu; Patel, Sravan Kumar; Zhou, Tian; Rohan, Lisa C

2015-12-10

Efflux and uptake transporters of drugs are key regulators of the pharmacokinetics of many antiretroviral drugs. A growing body of literature has revealed the expression and functionality of multiple transporters in female genital tract (FGT), colorectal tissue, and immune cells. Drug transporters could play a significant role in the efficacy of preventative strategies for HIV-1 acquisition. Pre-exposure prophylaxis (PrEP) is a promising strategy, which utilizes topically (vaginally or rectally), orally or other systemically administered antiretroviral drugs to prevent the sexual transmission of HIV to receptive partners. The drug concentration in the receptive mucosal tissues and target immune cells for HIV is critical for PrEP effectiveness. Hence, there is an emerging interest in utilizing transporter information to explain tissue disposition patterns of PrEP drugs, to interpret inter-individual variability in PrEP drug pharmacokinetics and effectiveness, and to improve tissue drug exposure through modulation of the cervicovaginal, colorectal, or immune cell transporters. In this review, the existing literature on transporter expression, functionality and regulation in the transmission-related tissues and cells is summarized. In addition, the relevance of transporter function for drug delivery and strategies that could exploit transporters for increased drug concentration at target locales is discussed. The overall goal is to facilitate an understanding of drug transporters for PrEP optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

PubMed

Mieras, Liesbeth; Anthony, Richard; van Brakel, Wim; Bratschi, Martin W; van den Broek, Jacques; Cambau, Emmanuelle; Cavaliero, Arielle; Kasang, Christa; Perera, Geethal; Reichman, Lee; Richardus, Jan Hendrik; Saunderson, Paul; Steinmann, Peter; Yew, Wing Wai

2016-06-08

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

PrEP (Pre-Exposure Prophylaxis) 101

MedlinePlus

... Español (Spanish) Recommend on Facebook Tweet Share Compartir Pre-exposure prophylaxis (or PrEP) is when people at ... A Brief Intro Protect yourself. Learn about PrEP (Pre-Exposure Prophylaxis) and how it works in this ...

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

Vaccines and bioterrorism: smallpox and anthrax.

PubMed

Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

2003-01-01

Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years.

PubMed

Zijenah, Lynn S; Katzenstein, David A; Nathoo, Kusum J; Rusakaniko, Simbarashe; Tobaiwa, Ocean; Gwanzura, Christine; Bikoue, Arsene; Nhembe, Margaret; Matibe, Petronella; Janossy, George

2005-02-01

BACKGROUND: Serologic tests for HIV infection in infants less than 18 months do not differentiate exposure and infection since maternally acquired IgG antibodies may be detected in infants. Thus, the gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. There is an urgent need to evaluate alternative and cost effective laboratory methods for early diagnosis of infant HIV-1 infection as well as identifying infected infants who may benefit from cotrimoxazole prophylaxis and/or initiation of highly active antiretroviral therapy. METHODS: Whole blood was collected in EDTA from 137 infants aged 0 to 18 months. DNA polymerase chain reaction was used as the reference standard for diagnosis of HIV-1 infection. T-cell subset profiles were determined by flow cytometry. RESULTS: Seventy-six infants were DNA PCR positive while 61 were negative. The median CD4 counts of PCR negative infants were significantly higher than those of the PCR positive infants, p < 0.001. The median CD4/CD8 ratio and the %CD4 of the PCR positive infants were both significantly lower than those of the negative infants, p < 0.001. The CD4/CD8 ratio had a >98% sensitivity for diagnosis of HIV-1 infection and a specificity of >98%. CONCLUSION: The CD4/CD8 ratio appears useful in identifying HIV-infected infants. The development of lower cost and more robust flow cytometric methods that provide both CD4/CD8 ratio and %CD4 may be cost-effective for HIV-1 diagnosis and identification of infants for cotrimoxazole prophylaxis and/or highly active antiretroviral therapy.

T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years

PubMed Central

Zijenah, Lynn S; Katzenstein, David A; Nathoo, Kusum J; Rusakaniko, Simbarashe; Tobaiwa, Ocean; Gwanzura, Christine; Bikoue, Arsene; Nhembe, Margaret; Matibe, Petronella; Janossy, George

2005-01-01

Background Serologic tests for HIV infection in infants less than 18 months do not differentiate exposure and infection since maternally acquired IgG antibodies may be detected in infants. Thus, the gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. There is an urgent need to evaluate alternative and cost effective laboratory methods for early diagnosis of infant HIV-1 infection as well as identifying infected infants who may benefit from cotrimoxazole prophylaxis and/or initiation of highly active antiretroviral therapy. Methods Whole blood was collected in EDTA from 137 infants aged 0 to 18 months. DNA polymerase chain reaction was used as the reference standard for diagnosis of HIV-1 infection. T-cell subset profiles were determined by flow cytometry. Results Seventy-six infants were DNA PCR positive while 61 were negative. The median CD4 counts of PCR negative infants were significantly higher than those of the PCR positive infants, p < 0.001. The median CD4/CD8 ratio and the %CD4 of the PCR positive infants were both significantly lower than those of the negative infants, p < 0.001. The CD4/CD8 ratio had a >98% sensitivity for diagnosis of HIV-1 infection and a specificity of >98%. Conclusion The CD4/CD8 ratio appears useful in identifying HIV-infected infants. The development of lower cost and more robust flow cytometric methods that provide both CD4/CD8 ratio and %CD4 may be cost-effective for HIV-1 diagnosis and identification of infants for cotrimoxazole prophylaxis and/or highly active antiretroviral therapy. PMID:15683549

Controversies in rabies vaccination.

PubMed

Ghosh, Tapan Kr

2003-06-01

Rabies is a cent per cent fatal disease and there should not be any controversy in giving rabies vaccine to the victims. WHO has fixed schedules for doses for both pre and post-exposure in different category of cases, which also help us to avoid all controversies. But controversies arise in five main areas, which are related to the strategies of rabies prevention. These are: (i) Replacing use of NTV by MTCV. (ii) Intradermal schedule of MTCV, in place of Essen protocol of 5 i.m. doses to reduce the cost. (iii) Acceptability and inclusion of pre-exposure doses of MTCV in the immunization schedule of children as additional vaccine (iv) Schedule for re-exposure in already post-exposure vaccinated cases and schedule for exposure in pre-exposure vaccinated cases. (v) Uses of RIG in WHO category III cases. If these controversial issues are considered scientifically, rabies prophylaxis will see the light of success.

The Danish PEP Registry: Experience with the use of post-exposure prophylaxis following blood exposure to HIV from 1999-2012.

PubMed

Lunding, Suzanne; Katzenstein, Terese L; Kronborg, Gitte; Storgaard, Merete; Pedersen, Court; Mørn, Birgitte; Lindberg, Jens Å; Kronborg, Thit M; Jensen, Janne

2016-01-01

The risk of occupational exposures to blood cannot be eliminated completely and access to post-exposure prophylaxis (PEP) to prevent HIV transmission is important. However, PEP administration has been associated with frequent adverse effects, low compliance and difficulties to ensure a proper risk assessment. This nationwide study describes 14 years of experience with the use of PEP following blood exposure in Denmark. A descriptive study of all PEP cases following non-sexual exposure to HIV in Denmark from 1999-2012. A total of 411 cases of PEP were described. There was a mean of 29.4 cases/year, increasing from 23 cases in 1999 to 49 cases in 2005 and then decreasing to 16 cases in 2012. Overall 67.2% of source patients were known to be HIV-positive at the time of PEP initiation, with no significant change over time. The median time to initiation of PEP was 2.5 h (0.15-28.5) following occupational exposure. Adverse effects were reported by 50.9% with no significant difference according to PEP regimen. In 85.1% of cases with available data, either a full course of PEP was completed or PEP was stopped because the source was tested HIV-negative. Only 6.6% stopped PEP early due to adverse effects. PEP in Denmark is generally prescribed according to the guidelines and the annual number of cases has declined since 2005. Adverse effects were common regardless of PEP regimens used and new drug regimens should be considered.

Feasibility of sustainable provision of intradermal post exposure prophylaxis against rabies at primary care level –evidence from rural Haryana

PubMed Central

2014-01-01

Background Rabies is the most severe and neglected public health problem in India. Management of animal bite with post exposure prophylaxis is the only existent strategy to prevent rabies related deaths. Cost-effective and sustainable programme for provision of post exposure prophylaxis (PEP) is needed in India. Methods In this study, we have documented the experience of implementation of intra-dermal anti rabies vaccination in Animal Bite Management (ABM) clinic at Primary Health Centre (PHC). This study facility belonged to Comprehensive Rural Health Services Project, Ballabgarh in Faridabad district of Haryana. Hospital service record of ABM clinic was analyzed and various feasibility issues such as costing of services, vaccine wastage and other operational issues in providing PEP services at PHC level were documented. Results A total of 619 patients were treated in the ABM clinic. Service utilization of ABM clinic was increased by 38% in the second year of implementation. Mean age of the patients was 23.9 years (SD: 18.8) and majority (70.4%) were males. Majority (86%) of the patients received the first dose of anti-rabies vaccine within the recommended 48 hours. A total 446 vaccine vials (1 ml) were consumed of which 20.8% was contributed in vaccine wastage. User-fee (350 Indian Rupees) collected from the patients. User-fee was re-used to purchase vaccines, intradermal (ID) syringes and other consumables required to ensure regular availability of ARV services at the PHC. Conclusions This study demonstrated the cost-effective and sustainable model of provision of PEP against rabies at primary care level. ID PEP provision at primary care level not only address the unmet need of animal bite management in the community also reduces the out of pocket expenditure of the patients. PMID:24965875

Introducing leprosy post-exposure prophylaxis into the health systems of India, Nepal and Indonesia: a case study.

PubMed

Tiwari, A; Mieras, L; Dhakal, K; Arif, M; Dandel, S; Richardus, J H

2017-09-29

Leprosy has a wide range of clinical and socio-economic consequences. India, Indonesia and Nepal contribute significantly to the global leprosy burden. After integration, the health systems are pivotal in leprosy service delivery. The Leprosy Post Exposure Prophylaxis (LPEP) program is ongoing to investigate the feasibility of providing single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) to the contacts of leprosy cases in various health systems. We aim to compare national leprosy control programs, and adapted LPEP strategies in India, Nepal and Indonesia. The purpose is to establish a baseline of the health system's situation and document the subsequent adjustment of LPEP, which will provide the context for interpreting the LPEP results in future. The study followed the multiple-case study design with single units of analysis. The data collection methods were direct observation, in-depth interviews and desk review. The study was divided into two phases, i.e. review of national leprosy programs and description of the LPEP program. The comparative analysis was performed using the WHO health system frameworks (2007). In all countries leprosy services including contact tracing is integrated into the health systems. The LPEP program is fully integrated into the established national leprosy programs, with SDR and increased documentation, which need major additions to standard procedures. PEP administration was widely perceived as well manageable, but the additional LPEP data collection was reported to increase workload in the first year. The findings of our study led to the recommendation that field-based leprosy research programs should keep health systems in focus. The national leprosy programs are diverse in terms of organizational hierarchy, human resource quantity and capacity. We conclude that PEP can be integrated into different health systems without major structural and personal changes, but provisions are necessary for the additional monitoring requirements.

Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin

PubMed Central

Barth-Jaeggi, Tanja; Steinmann, Peter; Mieras, Liesbeth; van Brakel, Wim; Richardus, Jan Hendrik; Tiwari, Anuj; Bratschi, Martin; Cavaliero, Arielle; Vander Plaetse, Bart; Mirza, Fareed; Aerts, Ann

2016-01-01

Introduction The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50–60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. Methods and analysis The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. Ethics and dissemination Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies. PMID:27856484

ACOG Committee Opinion No. 536: Human immunodeficiency virus and acquired immunodeficiency syndrome and women of color.

PubMed

2012-09-01

In the United States, most new cases of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) occur among women of color (primarily African American and Hispanic women). Most women of color acquire the disease from heterosexual contact, often from a partner who has undisclosed risk factors for HIV infection. Safe sex practices, especially consistent condom use, must be emphasized for all women, including women of color. A combination of testing, education, and brief behavioral interventions can help reduce the rate of HIV infection and its complications among women of color. In addition,biomedical interventions such as early treatment of patients infected with HIV and pre-exposure antiretroviral prophylaxis of high-risk individuals offer promise for future reductions in infections.

Re-emergence of animal rabies in northern Greece and subsequent human exposure, October 2012 - March 2013.

PubMed

Tsiodras, S; Dougas, G; Baka, A; Billinis, C; Doudounakis, S; Balaska, A; Georgakopoulou, T; Rigakos, G; Kontos, V; Tasioudi, K E; Tzani, M; Tsarouxa, P; Iliadou, P; Mangana-Vougiouka, O; Iliopoulos, D; Sapounas, S; Efstathiou, P; Tsakris, A; Hadjichristodoulou, C; Kremastinou, J

2013-05-02

Greece has been rabies-free since 1987 with no human cases since 1970. During 2012 to 2013, rabies has re-emerged in wild and domestic animals in northern Greece. By end March 2013, rabies was diagnosed in 17 animals including 14 red foxes, two shepherd dogs and one cat; 104 subsequent human exposures required post-exposure prophylaxis according to the World Health Organization criteria. Human exposures occurred within 50 km radius of a confirmed rabies case in a wild or domestic animal, and most frequently stray dogs were involved.

Differences in Awareness of Pre-exposure Prophylaxis and Post-exposure Prophylaxis Among Groups At-Risk for HIV in New York State: New York City and Long Island, NY, 2011-2013.

PubMed

Walters, Suzan M; Rivera, Alexis V; Starbuck, Lila; Reilly, Kathleen H; Boldon, Nyasha; Anderson, Bridget J; Braunstein, Sarah

2017-07-01

Pre-exposure prophylaxis (PrEP) to reduce the risk of HIV was approved in 2012 and post-exposure prophylaxis (PEP) in 2005. We report the differences in awareness of PrEP/PEP and factors associated with awareness by examining 3 risk groups (men who have sex with men (MSM), people who inject drugs, and high-risk heterosexuals). National HIV Behavioral Surveillance system data collected in New York City (NYC) and Long Island, NY in 2011-2013 were used. Logistic regressions by region were developed to estimate adjusted associations [Adjusted Odds Ratios (AOR)] and determine differences in awareness of PrEP/PEP. Awareness of PrEP/PEP was low for all groups. In multivariate analysis controlling for sociodemographic factors, noninjection drug use, HIV status, and exposure to HIV prevention, males who inject drugs in NYC had significantly decreased odds of PrEP/PEP awareness [AOR: 0.45; confidence interval (CI): 0.25 to 0.81] compared with MSM. MSM aged 18-29 years had increased awareness of PrEP (AOR: 2.94; 95% CI 1.11 to 7.80). On Long Island, females who inject drugs (AOR: 0.18; 95% CI: 0.05 to 0.62), males who inject drugs (AOR: 0.14; 95% CI: 0.05 to 0.39), female heterosexuals (AOR: 0.25; 95% CI: 0.11 to 0.59), and male heterosexuals (AOR: 0.32; 95% CI: 0.14 to 0.73) had significantly decreased odds of PrEP/PEP awareness. Black MSM had increased awareness of PrEP (AOR: 4.08 CI:1.21 to 13.73). Large proportions of groups at-risk for HIV were unaware of PrEP/PEP. When comparing risk groups to MSM, we found MSM to have greater awareness in both regions. On Long Island, people who inject drugs and heterosexuals were far less likely to have PrEP/PEP awareness than in NYC. On Long Island, Black MSM had increased PrEP awareness and in NYC MSM aged 18-29 had increased PrEP awareness. These findings suggest that awareness may be spreading through networks and highlight the importance of targeted educational and prevention efforts by group and region.

Evaluation of the duration of thromboembolic prophylaxis after high-risk orthopaedic surgery: the ETHOS observational study.

PubMed

Bergqvist, David; Arcelus, Juan I; Felicissimo, Paulo

2012-02-01

Real-life data on post-discharge venous thromboembolism (VTE) prophylaxis practices and treatments are lacking. We assessed post-operative VTE prophylaxis prescribed and received in a prospective registry, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in high-risk orthopaedic surgery patients. Consecutive patients undergoing total hip arthroplasty (THA), hip fracture surgery (HFS), or knee arthroplasty (KA) were enrolled at discharge from 161 centres in 17 European countries if they had received in-hospital VTE prophylaxis that was considered in accordance with the ACCP guidelines by the treating physician. Data on prescribed and actual prophylaxis were obtained from hospital charts and patient post-discharge diaries. Post-operative prophylaxis prescribed and actual prophylaxis received were considered adherent or adequate, respectively, if recommended therapies were used for ≥28 days (HFS and THA) or ≥10 days (KA). Among 4,388 patients, 69.9% were prescribed ACCP-adherent VTE prophylaxis (THA: 1,411/2,217 [63.6%]; HFS: 701/1,112 [63.0%]; KA: 955/1,059 [90.2%]). Actual prophylaxis received was described in 3,939 patients with an available diary after discharge (non-evaluability rate of 10%). Mean actual durations of pharmacological prophylaxis from surgery were: 28.4 ± 13.7 (THA), 29.3 ± 13.9 (HFS), and 28.7 ± 14.1 days (KA). ACCP-adequate VTE prophylaxis was received by 66.5% of patients (60.9% THA, 55.4% HFS, and 88.7% KA). Prophylaxis inadequacies were mainly due to inadequate prescription, non-recommended prophylaxis prescription at discharge, or too short prophylaxis prescribed. In high-risk orthopaedic surgery patients with hospital-initiated prophylaxis, there is a gap between ACCP recommendations, prescribed and actual prophylaxis received, mainly due to inadequate prescription at discharge.

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.

PubMed

De Benedictis, Paola; Minola, Andrea; Rota Nodari, Elena; Aiello, Roberta; Zecchin, Barbara; Salomoni, Angela; Foglierini, Mathilde; Agatic, Gloria; Vanzetta, Fabrizia; Lavenir, Rachel; Lepelletier, Anthony; Bentley, Emma; Weiss, Robin; Cattoli, Giovanni; Capua, Ilaria; Sallusto, Federica; Wright, Edward; Lanzavecchia, Antonio; Bourhy, Hervé; Corti, Davide

2016-04-01

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. © 2016 Humabs BioMed SA Published under the terms of the CC BY 4.0 license.

Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.

PubMed

Hakim, James; Musiime, Victor; Szubert, Alex J; Mallewa, Jane; Siika, Abraham; Agutu, Clara; Walker, Simon; Pett, Sarah L; Bwakura-Dangarembizi, Mutsa; Lugemwa, Abbas; Kaunda, Symon; Karoney, Mercy; Musoro, Godfrey; Kabahenda, Sheila; Nathoo, Kusum; Maitland, Kathryn; Griffiths, Anna; Thomason, Margaret J; Kityo, Cissy; Mugyenyi, Peter; Prendergast, Andrew J; Walker, A Sarah; Gibb, Diana M

2017-07-20

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups. Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. (Funded by the Medical Research Council and others; REALITY Current Controlled Trials number, ISRCTN43622374 .).

Provision of drugs for post-exposure prophylaxis of HIV for medical students on overseas electives.

PubMed

Franklin, G F; Gray, K; Nathwani, D

2001-10-01

To assess the need for, and the most practical way to provide, HIV post-exposure prophylaxis (PEP) for medical students travelling to areas where this is not readily available. Follow-up questionnaire for all 140 students from Dundee University returning from their medical elective in 2000, 22 of whom took triple therapy for PEP with them on elective. 103/140 students (74%) returned questionnaires. 76/103 (74%) were involved in exposure-prone procedures and 38/103 (37%) reported a significant exposure to potentially infective fluids. Six of this group considered PEP but none reported using it. The greatest perceived risk on elective remained road accidents. 87/103 respondents thought a 24-h helpline for health issues on electives would be useful. A high number of students report significant exposure to potentially infected fluids and this needs to be urgently addressed. There was almost unanimous endorsement of the idea of providing PEP and when it is made easily available prior to travel, students are willing to take it to areas where it is not available. In response to the survey, the investigators are looking at how to increase the current limited supply of PEP (Students may have to pay part of the cost) and the best way to provide a helpline, as it is felt that this could have a broad impact on student safety on electives, not just for issues involving PEP. Copyright 2001 The British Infection Society.

Reactions and Receptivity to Framing HIV Prevention Message Concepts About Pre-Exposure Prophylaxis for Black and Latino Men Who Have Sex with Men in Three Urban US Cities.

PubMed

Mimiaga, Matthew J; Closson, Elizabeth F; Battle, Shanice; Herbst, Jeffrey H; Denson, Damian; Pitts, Nicole; Holman, Jeremy; Landers, Stewart; Mansergh, Gordon

2016-10-01

Men who have sex with men (MSM) of color are disproportionately affected by HIV in the United States. Pre-exposure prophylaxis (PrEP) using antiretroviral medications is a newer biomedical prevention modality with established efficacy for reducing the risk of acquiring HIV. We conducted formative qualitative research to explore audience reactions and receptivity to message concepts on PrEP as part of the development of prevention messages to promote PrEP awareness among black and Latino MSM in the United States. In 2013, 48 black and 42 Latino (total study sample = 90) mixed HIV serostatus MSM from Chicago, Ft. Lauderdale, and Kansas City participated in either an individual interview or focus group discussion. Men were recruited online and at community-based organizations in each city. We elicited feedback on the comprehensibility, credibility, and relevance of two draft messages on PrEP. The messages included efficacy estimates from iPrEx, a phase III clinical trial to ascertain whether the antiretroviral medication tenofovir/emtricitabine disoproxil fumarate (commercially known as Truvada ® ) could safely and effectively prevent HIV acquisition through sex among MSM and transgender women. With participants' consent, the interviews and focus groups were recorded and transcribed. The data were then summarized and analyzed using a qualitative descriptive approach. The majority of men were unfamiliar with PrEP. It was suggested that additional information about the medication and clinical trials establishing efficacy was needed to enhance the legitimacy and relevancy of the messages. Participants sought to form an opinion of PrEP that was grounded in their own interpretation of the efficacy data. However, confusion about nonadherence among clinical trial subjects and individual versus average risk limited comprehension of these messages. Thematic overlaps suggest that message believability was connected to participants' ability to derive meaning from the PrEP efficacy data. Despite being concerned that other MSM would interpret the messages to mean that condom use was unnecessary while taking PrEP, participants themselves primarily understood PrEP as a supplement rather than a replacement for condoms. Based on their experience with taking antiretroviral medication, HIV-positive men considered condom use a more feasible form of HIV prevention than PrEP. Participants' responses suggest that more information about PrEP and the clinical trial would support the legitimacy of PrEP and the messages as a whole. These details may enhance believability in the concept of PrEP and reinforce confidence in the validity of the efficacy result.

Rabies: the clinical features, management and prevention of the classic zoonosis.

PubMed

Warrell, Mary J; Warrell, David A

2015-02-01

The diagnosis of rabies encephalitis relies on awareness of the varied clinical features and eliciting a history of unusual contact with a mammal throughout the endemic area. The diagnosis is easily missed. Laboratory tests are not routine and only confirm clinical suspicion. Rabies infection carries a case fatality exceeding 99.9%. Palliation is appropriate, except for previously-vaccinated patients or those infected by American bats, for whom intensive care is probably indicated. However, as rabies vaccines are outstandingly effective, no one should die of dog-transmitted infection. Vaccines and rabies immunoglobulin are expensive and usually scarce in Asia and Africa. All travellers to dog rabies enzootic areas should be strongly encouraged to have pre-exposure immunisation before departure. There is no contraindication to vaccination but the cost can be prohibitive. Intradermal immunisation, using 0.1 ml and sharing vials of vaccine, is cheaper and is now permitted by UK regulations. Returning travellers may need post-exposure prophylaxis. Economical intradermal post-exposure vaccination is practicable and should be introduced into rural areas of Africa and Asia immediately. Eliminating rabies in dogs is now feasible and would dramatically reduce human mortality, if funds were made available. The high current economic burden of human prophylaxis would then be largely relieved. © 2015 Royal College of Physicians.

Pre-Exposure Prophylaxis YouTube Videos: Content Evaluation.

PubMed

Kecojevic, Aleksandar; Basch, Corey; Basch, Charles; Kernan, William

2018-02-16

Antiretroviral (ARV) medicines reduce the risk of transmitting the HIV virus and are recommended as daily pre-exposure prophylaxis (PrEP) in combination with safer sex practices for HIV-negative individuals at a high risk for infection, but are underused in HIV prevention. Previous literature suggests that YouTube is extensively used to share health information. While pre-exposure prophylaxis (PrEP) is a novel and promising approach to HIV prevention, there is limited understanding of YouTube videos as a source of information on PrEP. The objective of this study was to describe the sources, characteristics, and content of the most widely viewed PrEP YouTube videos published up to October 1, 2016. The keywords "pre-exposure prophylaxis" and "Truvada" were used to find 217 videos with a view count >100. Videos were coded for source, view count, length, number of comments, and selected aspects of content. Videos were also assessed for the most likely target audience. The total cumulative number of views was >2.3 million, however, a single Centers for Disease Control and Prevention video accounted for >1.2 million of the total cumulative views. A great majority (181/217, 83.4%) of the videos promoted the use of PrEP, whereas 60.8% (132/217) identified the specific target audience. In contrast, only 35.9% (78/217) of the videos mentioned how to obtain PrEP, whereas less than one third addressed the costs, side effects, and safety aspects relating to PrEP. Medical and academic institutions were the sources of the largest number of videos (66/217, 30.4%), followed by consumers (63/217, 29.0%), community-based organizations (CBO; 48/217, 22.1%), and media (40/217, 18.4%). Videos uploaded by the media sources were more likely to discuss the cost of PrEP (P<.001), whereas the use of PrEP was less likely to be promoted in videos uploaded by individual consumers (P=.002) and more likely to be promoted in videos originated by CBOs (P=.009). The most common target audience for the videos was gay and bisexual men. YouTube videos can be used to share reliable PrEP information with individuals. Further research is needed to identify the best practices for using this medium to promote and increase PrEP uptake. ©Aleksandar Kecojevic, Corey Basch, Charles Basch, William Kernan. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 16.02.2018.

Rape and HIV post-exposure prophylaxis: addressing the dual epidemics in South Africa.

PubMed

Kim, Julia C; Martin, Lorna J; Denny, Lynette

2003-11-01

In South Africa, a country notable for both a rapidly escalating AIDS epidemic and high levels of sexual violence, the issue of HIV post-exposure prophylaxis (PEP) following rape has recently come to the fore, and a policy supporting provision of PEP has been approved by the national government. This paper compares the conditions for providing PEP in Europe and North America with the conditions faced by two initiatives in South Africa, one serving a primarily rural base, and one urban. It is based on a review of the literature on sexual violence in South Africa and use of PEP following occupational and non-occupational exposure. It incorporates perspectives from in-depth interviews in 2000 with 18 key informants, including survivors of sexual violence, gender and HIV activists, domestic violence NGOs, rape crisis centres, physicians, lawyers, researchers and HIV/AIDS advisors in the Department of Health. The paper argues that given the scientific evidence for PEP, and the nature of the dual epidemics of HIV and sexual violence in South Africa, the public health and social justice rationale for implementing PEP equals and indeed exceeds that put forward in industrialised countries. However, delays in accessing PEP caused by the public justice system and lack of training for service providers constitute significant obstacles to effective implementation. In this respect, provision of PEP presents an opportunity to reform and strengthen existing services for post-rape care and to link attention to the epidemic of sexual violence to HIV/AIDS prevention.

Translating PrEP effectiveness into public health impact: key considerations for decision-makers on cost-effectiveness, price, regulatory issues, distributive justice and advocacy for access.

PubMed

Hankins, Catherine; Macklin, Ruth; Warren, Mitchell

2015-01-01

The extraordinary feat of proving the effectiveness of oral pre-exposure prophylaxis (PrEP) in clinical trials in different populations in a variety of settings may prove to have been easier than ensuring it is used well. Decision-makers must make difficult choices to realize the promise of antiretroviral prophylaxis for their countries. This paper outlines key economic, regulatory and distributive justice issues that must be addressed for effective and acceptable PrEP implementation. In considering the role that PrEP can play in combination prevention programmes, decision-makers must determine who can benefit most from PrEP, how PrEP can be provided safely and efficiently, and what kind of health system support will ensure successful implementation. To do this, they need contextualized information on disease burden by population, analyses of how PrEP services might best be delivered, and projections of the human resource and infrastructure requirements for each potential delivery model. There are cost considerations, varying cost-effectiveness results and regulatory challenges. The principles of ethics can inform thorny discussions about who should be prioritized for oral PrEP and how best to introduce it fairly. We describe the cost-effectiveness of PrEP in different populations at higher risk of HIV exposure, its price in low- and middle-income countries, and the current regulatory situation. We explore the principles of ethics that can inform resource allocation decision-making about PrEP anchored in distributive justice, at a time when universal access to antiretroviral treatment remains to be assured. We then highlight the role of advocacy in moving the PrEP agenda forward. The time is ripe now for decisions about whether, how and for whom PrEP should be introduced into a country's HIV response. It has the potential to contribute significantly to high impact HIV prevention if it is tailored to those who can most benefit from it and if current regulatory and pricing barriers can be overcome. Advocacy at all levels can help inform decision-making and push the access agenda to avert HIV infections among those at highest risk of HIV exposure. The benefits will accrue beyond the individual level to slow HIV transmission at the population level.

The Use of Chemoprophylaxis after Floods to Reduce the Occurrence and Impact of Leptospirosis Outbreaks.

PubMed

Schneider, Maria Cristina; Velasco-Hernandez, Jorge; Min, Kyung-Duk; Leonel, Deise Galan; Baca-Carrasco, David; Gompper, Matthew E; Hartskeerl, Rudy; Munoz-Zanzi, Claudia

2017-06-03

Record-breaking and devastating rainfall events have occurred in the past decade. Rain and floods are considered the main risk factors for leptospirosis and several outbreaks have been reported following extreme weather events. In such situations, one possible intervention to prevent leptospirosis cases in high-risk groups is the use of chemoprophylaxis. However, not enough evidence of its effect is available. The objectives of this study were to review the literature on the current practices of chemoprophylaxis for leptospirosis and to explore, using a mathematical model, how various chemoprophylaxis scenarios may affect the progression of a leptospirosis outbreak. Twenty-six peer-reviewed publications were selected (10 quantitative studies, two systematic reviews and 14 articles of other types). Oral doxycycline was the most used antibiotic for chemoprophylaxis of leptospirosis. Post-exposure prophylaxis was assessed in four studies following a natural disaster. Although evidence of the effectiveness of post-exposure prophylaxis is inconsistent, the direction of association supported a protective effect for morbidity and mortality. The theoretical model showed how the assumed benefit of chemoprophylaxis was influenced by the time and rate of administration. Future models should consider the heterogeneity of affected communities, improved estimates of the effect of chemoprophylaxis on leptospirosis infection and disease, as well as potential detrimental impacts. Additional research is critical to provide clear evidence-based recommendations for leptospirosis control during an outbreak. The results of this study suggest that chemoprophylaxis may provide some protection in reducing the number of leptospirosis cases after a high-risk exposure; however, the effective benefit may depend on a variety of factors such as the timing and coverage of prophylaxis. The information summarized can be used to support decision-making during a high-risk event.

The Use of Chemoprophylaxis after Floods to Reduce the Occurrence and Impact of Leptospirosis Outbreaks

PubMed Central

Schneider, Maria Cristina; Velasco-Hernandez, Jorge; Min, Kyung-duk; Leonel, Deise Galan; Baca-Carrasco, David; Gompper, Matthew E.; Hartskeerl, Rudy; Munoz-Zanzi, Claudia

2017-01-01

Record-breaking and devastating rainfall events have occurred in the past decade. Rain and floods are considered the main risk factors for leptospirosis and several outbreaks have been reported following extreme weather events. In such situations, one possible intervention to prevent leptospirosis cases in high-risk groups is the use of chemoprophylaxis. However, not enough evidence of its effect is available. The objectives of this study were to review the literature on the current practices of chemoprophylaxis for leptospirosis and to explore, using a mathematical model, how various chemoprophylaxis scenarios may affect the progression of a leptospirosis outbreak. Twenty-six peer-reviewed publications were selected (10 quantitative studies, two systematic reviews and 14 articles of other types). Oral doxycycline was the most used antibiotic for chemoprophylaxis of leptospirosis. Post-exposure prophylaxis was assessed in four studies following a natural disaster. Although evidence of the effectiveness of post-exposure prophylaxis is inconsistent, the direction of association supported a protective effect for morbidity and mortality. The theoretical model showed how the assumed benefit of chemoprophylaxis was influenced by the time and rate of administration. Future models should consider the heterogeneity of affected communities, improved estimates of the effect of chemoprophylaxis on leptospirosis infection and disease, as well as potential detrimental impacts. Additional research is critical to provide clear evidence-based recommendations for leptospirosis control during an outbreak. The results of this study suggest that chemoprophylaxis may provide some protection in reducing the number of leptospirosis cases after a high-risk exposure; however, the effective benefit may depend on a variety of factors such as the timing and coverage of prophylaxis. The information summarized can be used to support decision-making during a high-risk event. PMID:28587195

Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

PubMed

Mujugira, Andrew; Baeten, Jared M; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R; Barnes, Linda; Campbell, James D; Wangisi, Jonathan; Tappero, Jordan W; Bukusi, Elizabeth; Cohen, Craig R; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kidoguchi, Lara; Panteleeff, Dana; Krows, Meighan; Shah, Heena; Revall, Jennifer; Morrison, Susan; Ondrejcek, Lisa; Ingram, Charlotte; Coombs, Robert W; Lingappa, Jairam R; Celum, Connie

2011-01-01

Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort. HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months. From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40) and (26-39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/µL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease. Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245).

Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir

PubMed Central

García-Lerma, J. Gerardo; Otten, Ron A; Qari, Shoukat H; Jackson, Eddie; Cong, Mian-er; Masciotra, Silvina; Luo, Wei; Kim, Caryn; Adams, Debra R; Monsour, Michael; Lipscomb, Jonathan; Johnson, Jeffrey A; Delinsky, David; Schinazi, Raymond F; Janssen, Robert; Folks, Thomas M; Heneine, Walid

2008-01-01

Background In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. Methods and Findings We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. Conclusions This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities. PMID:18254653

Effectiveness and Cost Effectiveness of Oral Pre-Exposure Prophylaxis in a Portfolio of Prevention Programs for Injection Drug Users in Mixed HIV Epidemics

PubMed Central

Alistar, Sabina S.; Owens, Douglas K.; Brandeau, Margaret L.

2014-01-01

Background Pre-exposure prophylaxis with oral antiretroviral treatment (oral PrEP) for HIV-uninfected injection drug users (IDUs) is potentially useful in controlling HIV epidemics with a significant injection drug use component. We estimated the effectiveness and cost effectiveness of strategies for using oral PrEP in various combinations with methadone maintenance treatment (MMT) and antiretroviral treatment (ART) in Ukraine, a representative case for mixed HIV epidemics. Methods and Findings We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs who inject opiates, and IDUs in MMT, adding an oral PrEP program (tenofovir/emtricitabine, 49% susceptibility reduction) for uninfected IDUs. We analyzed intervention portfolios consisting of oral PrEP (25% or 50% of uninfected IDUs), MMT (25% of IDUs), and ART (80% of all eligible patients). We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, HIV infections averted, and incremental cost effectiveness. A combination of PrEP for 50% of IDUs and MMT lowered HIV prevalence the most in both IDUs and the general population. ART combined with MMT and PrEP (50% access) averted the most infections (14,267). For a PrEP cost of $950, the most cost-effective strategy was MMT, at $520/QALY gained versus no intervention. The next most cost-effective strategy consisted of MMT and ART, costing $1,000/QALY gained compared to MMT alone. Further adding PrEP (25% access) was also cost effective by World Health Organization standards, at $1,700/QALY gained. PrEP alone became as cost effective as MMT at a cost of $650, and cost saving at $370 or less. Conclusions Oral PrEP for IDUs can be part of an effective and cost-effective strategy to control HIV in regions where injection drug use is a significant driver of the epidemic. Where budgets are limited, focusing on MMT and ART access should be the priority, unless PrEP has low cost. PMID:24489747

Rabies in an Arctic fox on the Svalbard archipelago, Norway, January 2011.

PubMed

Orpetveit, I; Ytrehus, B; Vikoren, T; Handeland, K; Mjos, A; Nissen, S; Blystad, H; Lund, A

2011-02-17

We report a case of rabies in an Arctic fox. In January 2011 a fox attacked dogs belonging to a meteorological station in the Svalbard archipelago, Norway. Rabies virus was detected in the fox's brain post-mortem. The dogs had been vaccinated against rabies and their antibody levels were protective. Post-exposure prophylaxis was administered to staff at the station. Rabies vaccination is recommended for inhabitants and visitors to the Arctic who may be in contact with wild animals.

Tenofovir-based Pre-Exposure Prophylaxis for HIV Prevention: Evidence and evolving questions

PubMed Central

Celum, Connie; Baeten, Jared

2012-01-01

Purpose of review Topical tenofovir gel and oral tenofovir and emtricitabine/tenofovir (FTC/TDF) have been demonstrated to have efficacy in preventing HIV-1 in some populations. Pre-exposure prophylaxis (PrEP) trials and future directions are summarized. Recent findings Peri-coital use of 1% tenofovir gel in CAPRISA 004 reduced HIV-1 acquisition by 39% and HSV-2 acquisition by 51%. Daily oral FTC/TDF demonstrated 44% reduction in HIV-1 acquisition among men who have sex with men (MSM) in iPrEx. Both studies showed higher efficacy among those with higher adherence. Efficacy of daily oral TDF and FTC/TDF was 66% and 73%, respectively, among HIV-1 uninfected partners in an HIV-1 serodiscordant partnership in the Partners PrEP Study. Efficacy of daily oral FTC/TDF was 66% in young heterosexuals in Botswana in the TDF-2 trial. The FEM-PrEP and VOICE studies in African women found no efficacy with oral FTC/TDF and TDF, respectively. Safety and tolerability were excellent and limited resistance was observed in seroconverters. Summary Topical tenofovir gel showed efficacy in African women and daily oral TDF and FTC/TDF were efficacious in MSM, and African HIV-1 serodiscordant couples and young heterosexuals. The reasons for lack of efficacy of oral FTC/TDF and TDF in two studies in African women are being investigated. Longer-acting formulations, invtravaginal rings, and new candidate antiretrovirals are being evaluated. PMID:22156901

Economic evaluation of HIV pre-exposure prophylaxis among men-who-have-sex-with-men in England in 2016.

PubMed

Ong, Koh Jun; Desai, Sarika; Field, Nigel; Desai, Monica; Nardone, Anthony; van Hoek, Albert Jan; Gill, Owen Noel

2017-10-01

Clinical effectiveness of pre-exposure prophylaxis (PrEP) for preventing HIV acquisition in men who have sex with men (MSM) at high HIV risk is established. A static decision analytical model was constructed to inform policy prioritisation in England around cost-effectiveness and budgetary impact of a PrEP programme covering 5,000 MSM during an initial high-risk period. National genitourinary medicine clinic surveillance data informed key HIV risk assumptions. Pragmatic large-scale implementation scenarios were explored. At 86% effectiveness, PrEP given to 5,000 MSM at 3.3 per 100 person-years annual HIV incidence, assuming risk compensation (20% HIV incidence increase), averted 118 HIV infections over remaining lifetimes and was cost saving. Lower effectiveness (64%) gave an incremental cost-effectiveness ratio of + GBP 23,500 (EUR 32,000) per quality-adjusted life year (QALY) gained. Investment of GBP 26.9 million (EUR 36.6 million) in year-1 breaks even anywhere from year-23 (86% effectiveness) to year-33 (64% effectiveness). PrEP cost-effectiveness was highly sensitive to year-1 HIV incidence, PrEP adherence/effectiveness, and antiretroviral drug costs. There is much uncertainty around HIV incidence in those given PrEP and adherence/effectiveness, especially under programme scale-up. Substantially reduced PrEP drug costs are needed to give the necessary assurance of cost-effectiveness, and for an affordable public health programme of sufficient size.

Southern African guidelines on the safe use of pre-exposure prophylaxis in persons at risk of acquiring HIV-1 infection

PubMed Central

Rebe, Kevin; Venter, Francois; Maartens, Gary; Moorhouse, Michelle; Conradie, Francesca; Wallis, Carole; Black, Vivian; Harley, Beth; Eakles, Robyn

2016-01-01

The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP) guidelines in June 2012 for men who have sex with men (MSM) who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO) Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines. PMID:29568613

HIV providers' likelihood to prescribe pre-exposure prophylaxis (PrEP) for HIV prevention differs by patient type: a short report.

PubMed

Adams, Leah M; Balderson, Benjamin H

2016-09-01

Pre-exposure prophylaxis (PrEP), the antiretroviral treatment regimen for HIV-negative people at high risk of acquiring HIV, has demonstrated efficacy across clinical trials in several patient populations. The Centers for Disease Control (CDC) have released detailed guidelines to aid providers in prescribing PrEP for their high-risk patients, including men who have sex with men (MSM), high-risk heterosexuals, and injection drug users (IDUs). Given that much attention in PrEP has focused on MSM patients, the present study used an online survey to assess factors involved in HIV care providers' (n = 363) decisions about prescribing PrEP, along with their willingness to prescribe PrEP to patients from various risk populations (e.g., MSM, heterosexuals, IDUs). The efficacy of PrEP was an important factor in providers' decisions about prescribing PrEP, as were considerations about patients' adherence to the regimen, regular follow-up for care, and medication costs. This survey's findings also suggest that providers' willingness to prescribe PrEP varies by patient group, with providers most willing to initiate the regimen with MSM who have an HIV-positive partner, and least willing to prescribe to high-risk heterosexuals or IDUs. In the context of the current CDC recommendations for PrEP that include MSM, heterosexuals, and IDUs, examining providers' rationales for and barriers against supporting this HIV prevention strategy across patient groups merits further attention.

Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers.

PubMed

Lipshultz, Steven E; Williams, Paige L; Zeldow, Bret; Wilkinson, James D; Rich, Kenneth C; van Dyke, Russell B; Seage, George R; Dooley, Laurie B; Kaltman, Jonathan R; Siberry, George K; Mofenson, Lynne M; Shearer, William T; Colan, Steven D

2015-01-02

We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs. There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores. There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.

Discontinuing Pneumocystis jirovecii Pneumonia Prophylaxis in HIV-Infected Patients With a CD4 Cell Count <200 cells/mm3.

PubMed

Sidhu, Vaninder K; Foisy, Michelle M; Hughes, Christine A

2015-12-01

To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3). We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation. All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included. Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV-infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART). Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART. © The Author(s) 2015.

Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis.

PubMed

Kuhar, David T; Henderson, David K; Struble, Kimberly A; Heneine, Walid; Thomas, Vasavi; Cheever, Laura W; Gomaa, Ahmed; Panlilio, Adelisa L

2013-09-01

This report updates US Public Health Service recommendations for the management of healthcare personnel (HCP) who experience occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV). Although the principles of exposure management remain unchanged, recommended HIV postexposure prophylaxis (PEP) regimens and the duration of HIV follow-up testing for exposed personnel have been updated. This report emphasizes the importance of primary prevention strategies, the prompt reporting and management of occupational exposures, adherence to recommended HIV PEP regimens when indicated for an exposure, expert consultation in management of exposures, follow-up of exposed HCP to improve adherence to PEP, and careful monitoring for adverse events related to treatment, as well as for virologic, immunologic, and serologic signs of infection. To ensure timely postexposure management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns, and institutions should take steps to ensure that staff are aware of both the importance of and the institutional mechanisms available for reporting and seeking care for such exposures. The following is a summary of recommendations: (1) PEP is recommended when occupational exposures to HIV occur; (2) the HIV status of the exposure source patient should be determined, if possible, to guide need for HIV PEP; (3) PEP medication regimens should be started as soon as possible after occupational exposure to HIV, and they should be continued for a 4-week duration; (4) new recommendation-PEP medication regimens should contain 3 (or more) antiretroviral drugs (listed in Appendix A ) for all occupational exposures to HIV; (5) expert consultation is recommended for any occupational exposures to HIV and at a minimum for situations described in Box 1 ; (6) close follow-up for exposed personnel ( Box 2 ) should be provided that includes counseling, baseline and follow-up HIV testing, and monitoring for drug toxicity; follow-up appointments should begin within 72 hours of an HIV exposure; and (7) new recommendation-if a newer fourth-generation combination HIV p24 antigen-HIV antibody test is utilized for follow-up HIV testing of exposed HCP, HIV testing may be concluded 4 months after exposure ( Box 2 ); if a newer testing platform is not available, follow-up HIV testing is typically concluded 6 months after an HIV exposure.

Systematic review and meta-analysis of secondary prophylaxis for prevention of HIV-related toxoplasmic encephalitis relapse using trimethoprim-sulfamethoxazole.

PubMed

Connolly, Mark P; Haitsma, Gertruud; Hernández, Adrián V; Vidal, José E

2017-09-01

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.

Post-Travel Consultations in a Regional Hub City Hospital, Japan.

PubMed

Yaita, Kenichiro; Sakai, Yoshiro; Iwahashi, Jun; Masunaga, Kenji; Hamada, Nobuyuki; Watanabe, Hiroshi

2016-01-01

To clarify the characteristics of post-travel consultation services in Japan, particularly in the provinces, we analyzed our post-travel patients in the travel clinic of Kurume University Hospital located in Kurume City (a regional hub City in southwestern Japan). Sixty post-travel patients visited our clinic between April 2008 and October 2014 and participated in this study: 55 were Japanese and five were foreign. We summarized and compared the characteristics of the patients after dividing the Japanese participants into long-term travelers (>14 days) and short-term travelers (≤14 days). The foreign travelers were described in a separate analysis. Of the 55 Japanese travelers, the mean age (± standard deviation) was 37.3 ± 16.3 years, and 36 patients (65%) were men. Southeast Asia was the major destination (30/55, 55%), and business was stated as the major reason for travel (16/55, 29%). Post-exposure rabies prophylaxis (16/55, 29%) was the most common purpose for the consultations. There were 34 participants (62%) who were classified as short-term travelers. Fewer of the short-term travelers stated receiving pre-travel consultations compared with long-term travelers (11% vs. 79%, p=0.0002). The five foreign travelers included one dengue fever patient and two malaria patients. Most post-travel Japanese patients visited our clinic were short-term travelers who had not received any pre-travel consultation. One of the most common complaints, post-exposure rabies prophylaxis, could have been avoided to some extent by appropriate pre-travel consultations. The results of this study suggest that pre-travel consultations should therefore be encouraged for both long- and short-term travelers.

Post-exposure prophylaxis use and recurrent exposure to HIV among men who have sex with men who use crystal methamphetamine

PubMed Central

Oldenburg, Catherine E.; Jain, Sachin; Mayer, Kenneth H.; Mimiaga, Matthew J.

2014-01-01

Background Men who have sex with men (MSM) who use crystal methamphetamine (CM) are at increased risk for HIV infection. Post-exposure prophylaxis (PEP) is a useful HIV prevention strategy if individuals are able to identify high-risk exposures and seek timely care, however to date there has been limited data on the use of PEP by CM users. Methods A retrospective cohort study of all PEP prescriptions (N=1,130 prescriptions among 788 MSM) at Fenway Community Health in Boston, MA was undertaken. Multivariable models were used to assess the association between CM use during exposure (7.4% used CM during exposure) and chronically (7.4% of MSM were chronic CM users) and individual-level and event-level outcomes among MSM who used PEP at least once. Results Compared to those who had not used CM, MSM PEP users who used CM more frequently returned for repeat PEP (aOR 5.13, 95%CI 2.82 to 9.34) and were significantly more likely to seroconvert over the follow-up period (aHR 3.61, 95%CI 1.51 to 8.60). MSM who used CM had increased odds of unprotected anal intercourse as the source of exposure (aOR 2.12, 95%CI 1.16 to 3.87) and knowing that their partner was HIV infected (aOR 2.27, 95%CI 1.42 to 3.64). Conclusions While MSM who use CM may have challenges accessing ART in general, these data highlight the fact that those who were able to access PEP subsequently remained at increased risk of HIV seroconversion Counseling and/or substance use interventions during the PEP course should be considered for CM-using MSM. PMID:25482500

API consensus guidelines for use of antiretroviral therapy in adults (API-ART guidelines). Endorsed by the AIDS Society of India.

PubMed

Gupta, S B; Pujari, S N; Joshi, S R; Patel, A K

2006-01-01

With rational use of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been transformed into a chronic manageable illness like diabetes and hypertension. These guidelines provide information on state of art, evidence based approach for use of ART in Indian context. When to initiate ART? Antiretroviral therapy is indicated for all symptomatic HIV infected persons regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic patients, ART should be offered when the CD4 counts < 200/mm3 and should be considered in patients with CD4 counts between 200-250/mm3. Therapy is not recommended for patients with CD4 count more than 350/ mm3. Involvement of patient in all treatment decisions and assessing readiness is critical before initiating ART. What to start with? A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is recommended for antiretroviral naïve patients. The choice between nevirapine and efavirenz is based on differences in adverse events profiles; cost and availability of convenient fixed dose combinations and need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations and ART strategies not to be used in clinical practice has been enlisted. How to follow up? Recommendations have been made for baseline evaluation and monitoring of patients on ART. These include guidelines on laboratory and clinical evaluation. A plasma viral load at 6 months after initiation of first-line ART is strongly recommended. Yearly estimation of lipid profile has been recommended. How to identify and manage ART failure? The guidelines recognize the issue of identifying ART failure late if only CD4 counts are used for monitoring. In the absence of resistance testing various second-line regimens have been enlisted. A boosted protease inhibitor based regimen is recommended in this situation to be combined with 2-NRTIs. Special situations Recommendations have been made for use of ART in HIV-TB, HIV-HBV, and HIV-HCV co-infected patients. In patients with active TB and a CD4 count < 200/mm3, initiation of ART is recommended as soon as the anti-TB treatment is tolerated. Efavirenz is the only ARV drug, which can be safely used with rifampicin. In pregnancy use of single dose nevirapine for reducing risk of mother to child transmission of HIV is not recommended, because of the risk of development of resistance. For post-exposure prophylaxis taking ART treatment history of the source patient is crucial in designing an effective regimen.

HIV serodiscordant relationships in India: translating science to practice.

PubMed

Solomon, Sunil Suhas; Solomon, Suniti

2011-12-01

Over the past 30 years, several interventions have been identified to prevent HIV transmission from HIV-infected persons to uninfected persons in discordant relationships. Yet, transmissions continue to occur. Interventions such as voluntary counselling and testing, condom promotion and risk reduction counselling are very effective in preventing transmission among serodiscordant couples but are underutilized in India despite their widespread availability. New interventions such as pre-risk exposure prophylaxis and universal antiretroviral therapy (irrespective of CD4 count) have been newly identified but face several challenges that impede their widespread implementation in India. Discordant couples in India also face certain unique socio-cultural issues such as marital and fertility pressure. We briefly review the various interventions (existing and novel) available for persons in discordant relationships in India and socio-cultural issues faced by these individuals and make recommendations to maximize their implementation.

Impact of pharmacy technician-centered medication reconciliation on optimization of antiretroviral therapy and opportunistic infection prophylaxis in hospitalized patients with HIV/AIDS.

PubMed

Siemianowski, Laura A; Sen, Sanchita; George, Jomy M

2013-08-01

This study aimed to examine the role of a pharmacy technician-centered medication reconciliation (PTMR) program in optimization of medication therapy in hospitalized patients with HIV/AIDS. A chart review was conducted for all inpatients that had a medication reconciliation performed by the PTMR program. Adult patients with HIV and antiretroviral therapy (ART) and/or the opportunistic infection (OI) prophylaxis listed on the medication reconciliation form were included. The primary objective is to describe the (1) number and types of medication errors and (2) the percentage of patients who received appropriate ART. The secondary objective is a comparison of the number of medication errors between standard mediation reconciliation and a pharmacy-led program. In the PTMR period, 55 admissions were evaluated. In all, 50% of the patients received appropriate ART. In 27of the 55 admissions, there were 49 combined ART and OI-related errors. The most common ART-related errors were drug-drug interactions. The incidence of ART-related medication errors that included drug-drug interactions and renal dosing adjustments were similar between the pre-PTMR and PTMR groups (P = .0868). Of the 49 errors in the PTMR group, 18 were intervened by a medication reconciliation pharmacist. A PTMR program has a positive impact on optimizing ART and OI prophylaxis in patients with HIV/AIDS.

Isoniazid for preventing tuberculosis in HIV-infected children

PubMed Central

Zunza, Moleen; Gray, Diane M; Young, Taryn; Cotton, Mark; Zar, Heather J

2017-01-01

Background Tuberculosis (TB) is an important cause of illness and death in HIV-positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV-negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV-positive children. Objectives To summarise the effects of TB preventive treatment versus placebo in HIV-positive children with no known TB contact on active TB, death, and reported adverse events. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017. Selection criteria We included trials of HIV-positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo. Data collection and analysis Two review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE. Main results We included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow-up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART). In HIV-positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported. In HIV-positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups. Authors' conclusions Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV-positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. . Isoniazid prophylaxis for preventing active tuberculosis and death in HIV-positive children What was the aim of this review? To summarise the effects of isoniazid prophylaxis on TB, death, and adverse effects in HIV-positive children. Key messages In areas of high tuberculosis endemicity, isoniazid prophylaxis prevents active TB and death in HIV-positive children who are not on ART. We conducted a review to assess the effect of TB medication on active TB or death and its safety in HIV-positive children. What was studied in the review? TB is a common cause of severe lung disease and death in HIV-positive children. Childhood TB is common in poor countries, especially those with a coexisting burden of HIV/AIDS disease. HIV-positive children have a higher risk of developing TB than HIV-negative children. Isoniazid prevents TB in HIV-positive adults and is currently used in children who are at high risk of developing TB disease after exposure to someone with TB. However, there is limited information on the effect of isoniazid medication in reducing active TB or death if given to HIV-positive children without known TB contact. We searched for studies up to 17 February 2017, and found three studies published between 2007 and 2014 that addressed the effect of isoniazid medication compared to no medication on active TB and death in 991 HIV-positive children, below the age of 13 years. Most of the children were on antiretroviral therapy (ART) and the studies were conducted in South Africa and Botswana. The median length of follow-up ranged from 5.7 to 34 months. What are the main results of the review? In HIV-positive children not taking ART, isoniazid medication reduced the number of children developing active TB by 69% (low certainty evidence), and death by 54% (low certainty evidence). One trial was conducted in HIV-positive children taking ART, and this did not detect any benefit or harm of isoniazid (very low certainty evidence). The number of children with adverse effects were similar in children receiving isoniazid medication as the control group in both children on ART and not on ART. How up to date is the review? The review authors searched for studies published up to February 2017. PMID:28850172

Rabies transmission risks during peripartum--Two cases and a review of the literature.

PubMed

Aguèmon, Christiane Tshabu; Tarantola, Arnaud; Zoumènou, Eugène; Goyet, Sophie; Assouto, Pamphile; Ly, Sowath; Mewanou, Serge; Bourhy, Hervé; Dodet, Betty; Aguèmon, Abdou-Rahmann

2016-04-04

We report two cases of probable rabies in near-term/at-term pregnant women in sub-Saharan Africa and Asia. One baby was delivered by caesarean section and the other one vaginally. Both received post-exposure prophylaxis (PEP), including RIG and vaccine and both are alive and healthy, at 9 and 24 months, respectively. We found 14 other published cases of infants born from rabid mothers. One confirmed case of rabies transmission occurred. The other children born from rabid mothers, with or without caesarean section, did not acquire rabies, and were still healthy at the time of reporting, with or without post-exposure prophylaxis. Mother-to-child transmission of rabies is possible, but rare, because rabies virus is not present in blood and exposure of the baby's mucosa to maternal infectious fluids and tissue seems limited. A conservative approach should however, be adopted, and rabies PEP, including RIG, be administered as soon as possible to babies born from probably rabid mothers. Whether cesarean-section clearly provides prevention remains unclear. Rabies can be prevented in pregnant women by PEP administration. Rabies cell-culture vaccines are safe and effective and can be administered to pregnant and lactating women, as well as newborns. Efforts must focus on raising rabies awareness in the general population, as well as in healthcare workers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pre-Exposure Prophylaxis YouTube Videos: Content Evaluation

PubMed Central

Basch, Corey; Basch, Charles; Kernan, William

2018-01-01

Background Antiretroviral (ARV) medicines reduce the risk of transmitting the HIV virus and are recommended as daily pre-exposure prophylaxis (PrEP) in combination with safer sex practices for HIV-negative individuals at a high risk for infection, but are underused in HIV prevention. Previous literature suggests that YouTube is extensively used to share health information. While pre-exposure prophylaxis (PrEP) is a novel and promising approach to HIV prevention, there is limited understanding of YouTube videos as a source of information on PrEP. Objective The objective of this study was to describe the sources, characteristics, and content of the most widely viewed PrEP YouTube videos published up to October 1, 2016. Methods The keywords “pre-exposure prophylaxis” and “Truvada” were used to find 217 videos with a view count >100. Videos were coded for source, view count, length, number of comments, and selected aspects of content. Videos were also assessed for the most likely target audience. Results The total cumulative number of views was >2.3 million, however, a single Centers for Disease Control and Prevention video accounted for >1.2 million of the total cumulative views. A great majority (181/217, 83.4%) of the videos promoted the use of PrEP, whereas 60.8% (132/217) identified the specific target audience. In contrast, only 35.9% (78/217) of the videos mentioned how to obtain PrEP, whereas less than one third addressed the costs, side effects, and safety aspects relating to PrEP. Medical and academic institutions were the sources of the largest number of videos (66/217, 30.4%), followed by consumers (63/217, 29.0%), community-based organizations (CBO; 48/217, 22.1%), and media (40/217, 18.4%). Videos uploaded by the media sources were more likely to discuss the cost of PrEP (P<.001), whereas the use of PrEP was less likely to be promoted in videos uploaded by individual consumers (P=.002) and more likely to be promoted in videos originated by CBOs (P=.009). The most common target audience for the videos was gay and bisexual men. Conclusions YouTube videos can be used to share reliable PrEP information with individuals. Further research is needed to identify the best practices for using this medium to promote and increase PrEP uptake. PMID:29467119

Anaemia in Pregnancy Is Associated with Advanced HIV Disease

PubMed Central

Nandlal, Vikesh; Moodley, Dhayendre; Grobler, Anneke; Bagratee, Jayanthilall; Maharaj, Niren R.; Richardson, Paul

2014-01-01

Background Anaemia is a common clinical finding in HIV infected women and has been associated with advanced disease. The use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia. We report the prevalence, type, severity and incidence of anaemia in a cohort of HIV infected women who initiated antiretroviral prophylaxis or treatment during pregnancy. Methods and Materials This is a retrospective cohort data analysis of 408 HIV infected pregnant women who participated in a breastfeeding intervention study (HPTN 046 Study, ClinicalTrials.gov NCT 00074412) in South Africa. Women initiated zidovudine prophylaxis for PMTCT or triple antiretroviral treatment in pregnancy according to the standard of care. Laboratory and clinical data in pregnancy, <72 hours and 2 weeks postdelivery were extracted from the main database and analysed. Results The mean Hb concentration was 10.6 g/dL at baseline and 262/408 (64.2%) women were diagnosed with anaemia (Hb<11 g/dL) in pregnancy, 48/146 (32.9%) subsequently developed anaemia intrapartum or postpartum and 89/310 (28.7%) of all cases of anaemia remained unresolved by 2 weeks postdelivery. In a univariate analysis, CD4 count and gravidity were significant risk factors for anaemia in pregnancy, RR 1.41; 1.23–1.61 (p<0.001) and 1.10; 1.01–1.18 (p = 0.02) respectively. After adjusting for antiretroviral regimen, age and gravidity in a multivariable analysis, only the CD4 count remains a significant risk factor for anaemia in pregnancy and postdelivery. Conclusion In conclusion, anaemia was most common among women in the advanced stage of HIV infection (CD4<200 cells/mm3). There was no evidence of an association between ZDV or triple ARVs and anaemia. PMID:25222119

Anaemia in pregnancy is associated with advanced HIV disease.

PubMed

Nandlal, Vikesh; Moodley, Dhayendre; Grobler, Anneke; Bagratee, Jayanthilall; Maharaj, Niren R; Richardson, Paul

2014-01-01

Anaemia is a common clinical finding in HIV infected women and has been associated with advanced disease. The use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia. We report the prevalence, type, severity and incidence of anaemia in a cohort of HIV infected women who initiated antiretroviral prophylaxis or treatment during pregnancy. This is a retrospective cohort data analysis of 408 HIV infected pregnant women who participated in a breastfeeding intervention study (HPTN 046 Study, ClinicalTrials.gov NCT 00074412) in South Africa. Women initiated zidovudine prophylaxis for PMTCT or triple antiretroviral treatment in pregnancy according to the standard of care. Laboratory and clinical data in pregnancy, <72 hours and 2 weeks postdelivery were extracted from the main database and analysed. The mean Hb concentration was 10.6 g/dL at baseline and 262/408 (64.2%) women were diagnosed with anaemia (Hb<11 g/dL) in pregnancy, 48/146 (32.9%) subsequently developed anaemia intrapartum or postpartum and 89/310 (28.7%) of all cases of anaemia remained unresolved by 2 weeks postdelivery. In a univariate analysis, CD4 count and gravidity were significant risk factors for anaemia in pregnancy, RR 1.41; 1.23-1.61 (p<0.001) and 1.10; 1.01-1.18 (p = 0.02) respectively. After adjusting for antiretroviral regimen, age and gravidity in a multivariable analysis, only the CD4 count remains a significant risk factor for anaemia in pregnancy and postdelivery. In conclusion, anaemia was most common among women in the advanced stage of HIV infection (CD4<200 cells/mm3). There was no evidence of an association between ZDV or triple ARVs and anaemia.

[Clinical management of acute and chronic human immunodeficiency virus infection before starting antiretroviral treatment].

PubMed

Miró, José M; Manzardo, Christian; Zamora, Laura; Pumarola, Tomas; Herreras, Zoe; Gallart, Teresa; Gatell, José M

2011-12-01

The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Assessment of duration of staying free from acquiring rehappening opportunistic infections among pre-ART people living with HIV/AIDS between 2008 and 2013.

PubMed

Bizuayehu, Habtamu Mellie; Abyu, Direslgne Misker; Aweke, Amlaku Mulat

2015-01-01

Introduction. In regional state of the study area, HIV (Human Immunodeficiency Virus) prevalence is 2.2% and opportunistic infections (OIs) occurred in 88.9% of pre-ART (Antiretroviral Therapy) people living with HIV/AIDS (PLWHA). Even though OIs are prevalent in the study area, duration of staying free from acquiring rehappening opportunistic infections and its determinant factors are not studied. Method. The study was conducted in randomly selected 341 adult Pre-ART PLWHA who are included in chronic HIV care. OI free duration was estimated using the actuarial life table and Kaplan Meier survival. Cox proportional-hazard model was used to calculate hazard rate. Result. OIs were rediagnosed in three quarters (75.37%) participants. In each week the probability of getting new recurrence OI was about 15.04 per 1000 person weeks. The median duration of not acquiring OI recurrence was 54 weeks. After adjustment, variables associated with recurrence were employment status, marital status, exposure for prophylaxis and adherence to it, CD4 count, and hemoglobin value. Conclusion. Giving prophylaxis and counseling to adhere it, rise in CD4 and hemoglobin level, and enhancing job opportunities should be given for PLWHA who are on chronic HIV care while continuing the care.

Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single-Dose Nevirapine

PubMed Central

Micek, Mark A.; Blanco, Ana Judith; Beck, Ingrid A.; Dross, Sandra; Matunha, Laurinda; Montoya, Pablo; Seidel, Kristy; Gantt, Soren; Matediane, Eduardo; Jamisse, Lilia; Gloyd, Stephen; Frenkel, Lisa M.

2011-01-01

Background In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection. Methods We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time. Results Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P =.006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P =.001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P =.017, compared with established in utero infection). Conclusions The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals. PMID:20384494

Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin.

PubMed

Barth-Jaeggi, Tanja; Steinmann, Peter; Mieras, Liesbeth; van Brakel, Wim; Richardus, Jan Hendrik; Tiwari, Anuj; Bratschi, Martin; Cavaliero, Arielle; Vander Plaetse, Bart; Mirza, Fareed; Aerts, Ann

2016-11-17

The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Preliminary evidence of HIV seroconversion among HIV-negative men who have sex with men taking non-prescribed antiretroviral medication for HIV prevention in Miami, Florida, USA.

PubMed

Buttram, Mance E; Kurtz, Steven P

2017-04-01

Background Limited information suggests that men who have sex with men (MSM) are informally obtaining antiretroviral medication (ARVs) and using them for HIV pre-exposure prophylaxis (PrEP). Data are drawn from an on-going study examining the use of non-prescribed ARVs for PrEP. To date, 24 qualitative interviews have been conducted with HIV-negative, substance-using MSM living in Miami, Florida, USA. Data are presented from two participants who reported HIV seroconversion while using non-prescribed ARVs for PrEP. Preliminary data indicate that some young MSM: (i) lack awareness of and accurate information about the efficacious use of PrEP; (ii) obtain non-prescribed ARVs from HIV-positive sex partners and use these medications for PrEP in a way that does not provide adequate protection against HIV infection or cohere with established guidelines; and (iii) engage in multiple HIV transmission risk behaviours, including condomless anal sex and injection drug use. The informal, non-prescribed and non-medically supervised use of ARVs for HIV prevention has the potential to undermine the protective benefits of PrEP and leave men unprotected against HIV transmission and at risk for ARV resistance.

Antibodies for HIV Prevention in young women

PubMed Central

Abdool Karim, Salim S.; Karim, Quarraisha Abdool; Baxter, Cheryl

2016-01-01

Purpose of review Young women in sub-Saharan Africa bear a disproportionate HIV burden. They urgently require new HIV prevention approaches that women can use. This review provides an overview of the use of antiretrovirals for HIV pre-exposure prophylaxis (PrEP), highlighting some of the challenges with this technology and explores the potential role of monoclonal antibodies (mAbs) for HIV prevention in women. Recent findings Recent findings on the initial steps in viral entry and establishment of a productive local infectious nidus in the vaginal epithelium has provided important clues for HIV prevention in the female genital tract. Topical and oral formulations of antiretroviral drugs have been shown to prevent HIV infection in women with varying levels of success, depending principally on adherence. Further, a number of new broad and potent mAbs have been isolated over the last 5 years. Non-human primate studies demonstrate that broadly neutralizing HIV mAbs can protect rhesus macaques from SHIV infection. These findings have created newfound enthusiasm for passive immunization as a potential prevention strategy for women. Summary If potent broadly neutralising mAbs are effective in preventing HIV infection in women, it could fill an important gap in HIV prevention technologies for young women, especially in Africa. PMID:25700207

[Recommendations of the CEVIHP/SEIP/AEP/PNS on antiretroviral treatment in HIV-infected children and teenagers].

PubMed

Ramos, José Tomás; de José, María Isabel; Polo, Rosa; Fortuny, Claudia; Mellado, María José; Muñoz-Fernández, María Angeles; Beceiro, José; Bertrán, José María; Calvo, Cristina; Chamorro, Lourdes; Ciria, Luis; Guillén, Sara; González-Montero, Raúl; González-Tomé, María Isabel; Gurbindo, María Dolores; Martín-Fontelos, Pablo; Martínez-Pérez, Jorge; Moreno, David; Muñoz-Almagro, María Carmen; Mur, Antonio; Navarro, María Luisa; Otero, Carmen; Rojo, Pablo; Rubio, Bárbara; Saavedra, Jesús

2005-05-01

To update antiretroviral recommendations in antiretroviral therapy (ART) in HIV-infected children and adolescents. Theses guidelines have been formulated by a panel of members of the Plan Nacional sobre el SIDA (PNS) and the Asociacion Espanola de Pediatria (AEP) by reviewing the current available evidence of efficacy, safety, and pharmacokinetics in pediatric studies. Three levels of evidence have been defined according to the source of data: Level A: randomized and controlled studies; Level B: Cohort and case-control studies; Level C: Descriptive studies and experts' opinion. When to start ART should be made on an individual basis, discussed with the family, considering the risk of progression according to age, CD4 and viral load, the ART-related complications and adherence. The ART goal is to reach a maximum and durable viral suppression. This is not always possible, even with clinical and immunologic improvement. The difficulties of permanent adherence and side-effects are resulting in a more conservative trend to initiate ART, and to less toxic and simpler strategies. Currently, combinations of at least three drugs are of first choice both in acute and chronic infection. They must include 2 NA 1 1 NN or 2 NA 1 1 PI. ART is recommended in all symptomatic patients and, with few exceptions, in all infants in the first year of life. Older asymptomatic children should start ART according to CD4 count, especially CD4 percentage, that vary with age. Despite potent salvage therapies, it is common not to reach viral undetectability. Therapeutical options when ART fails are scarce due to cross-resistance. The cause of failure must be identified. Occasionally, there exists clinical and/or immunological progression, and a change of therapy with at least two new drugs still active for the patient, is warranted with the aim of increasing the CD4 count to a lower level of risk. Toxicity and adherence must be regularly monitored. Some aspects about post exposure prophylaxis and coinfection with HCV or HBV are discussed. A higher level of evidence with regard to ART effectiveness and toxicity in pediatrics is currently available, leading to a more conservative and individualized approach. Clinical symptoms and CD4 count are the main determinants to start and change ART.

Adverse Events Associated with Prolonged Antibiotic Use

PubMed Central

Meropol, Sharon B.; Chan, K. Arnold; Chen, Zhen; Finkelstein, Jonathan A.; Hennessy, Sean; Lautenbach, Ebbing; Platt, Richard; Schech, Stephanie D.; Shatin, Deborah; Metlay, Joshua P.

2014-01-01

Purpose The Infectious Diseases Society of America and US CDC recommend 60 days of ciprofloxacin, doxycycline or amoxicillin for anthrax prophylaxis. It is not possible to determine severe adverse drug event (ADE) risks from the few people thus far exposed to anthrax prophylaxis. This study’s objective was to estimate risks of severe ADEs associated with long-term ciprofloxacin, doxycycline and amoxicillin exposure using 3 large databases: one electronic medical record (General Practice Research Database) and two claims databases (UnitedHealthcare, HMO Research Network). Methods We include office visit, hospital admission and prescription data for 1/1/1999–6/30/2001. Exposure variable was oral antibiotic person-days (pds). Primary outcome was hospitalization during exposure with ADE diagnoses: anaphylaxis, phototoxicity, hepatotoxicity, nephrotoxicity, seizures, ventricular arrhythmia or infectious colitis. Results We randomly sampled 999,773, 1,047,496 and 1,819,004 patients from Databases A, B and C respectively. 33,183 amoxicillin, 15,250 ciprofloxacin and 50,171 doxycycline prescriptions continued ≥30 days. ADE hospitalizations during long-term exposure were not observed in Database A. ADEs during long-term amoxicillin were seen only in Database C with 5 ADEs or 1.2(0.4–2.7) ADEs/100,000 pds exposure. Long-term ciprofloxacin showed 3 and 4 ADEs with 5.7(1.2–16.6) and 3.5(1.0–9.0) ADEs/100,000 pds in Databases B and C, respectively. Only Database B had ADEs during long-term doxycycline with 3 ADEs or 0.9(0.2–2.6) ADEs/100,000 pds. For most events, the incidence rate ratio, comparing >28 vs.1–28 pds exposure was <1, showing limited evidence for cumulative dose-related ADEs from long-term exposure. Conclusions Long-term amoxicillin, ciprofloxacin and doxycycline appears safe, supporting use of these medications if needed for large-scale post-exposure anthrax prophylaxis. PMID:18215001

Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers.

PubMed

Jacobs, Michael; Aarons, Emma; Bhagani, Sanjay; Buchanan, Ruaridh; Cropley, Ian; Hopkins, Susan; Lester, Rebecca; Martin, Daniel; Marshall, Neal; Mepham, Stephen; Warren, Simon; Rodger, Alison

2015-11-01

Although a few international health-care workers who have assisted in the current Ebola outbreak in west Africa have been medically evacuated for treatment of Ebola virus disease, more commonly they were evacuated after potential accidental exposure to Ebola virus. An urgent need exists for a consensus about the risk assessment of Ebola virus transmission after accidental exposure, and to investigate the use of post-exposure prophylaxis (PEP). Experimental vaccines have occasionally been used for Ebola PEP, but newly developed experimental antiviral agents have potential advantages. Here, we describe a new method for risk assessment and management of health-care workers potentially exposed to Ebola virus and report the use of experimental antiviral therapies for Ebola PEP in people. We devised a risk assessment and management algorithm for health-care workers potentially exposed to Ebola virus and applied this to eight consecutive individuals who were medically evacuated to the UK from west Africa between January, and March, 2015. PEP with antiviral agents was given to health-care workers assessed to have had substantial risk exposures to Ebola virus. Participants were followed up for 42 days after potential exposure. Four of eight health-care workers were classified as having had low risk exposures and managed by watchful waiting in the community. None of these health-care workers developed Ebola virus disease. The other four health-care workers had intermediate or maximum risk exposures and were given PEP with antiviral agents. PEP was well tolerated with no serious adverse effects. None of these four health-care workers, including two with maximum risk exposures from penetrating injuries with freshly used hollow-bore needles, developed Ebola virus disease. Standardised risk assessment should be adopted and consensus guidelines developed to systematically study the efficacy and safety of PEP with experimental agents. New experimental antiviral treatments are a viable option for PEP against Ebola. Royal Free London NHS Foundation Trust. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increasing the Clinical Potential and Applications of Anti-HIV Antibodies

PubMed Central

Hua, Casey K.; Ackerman, Margaret E.

2017-01-01

Preclinical and early human clinical studies of broadly neutralizing antibodies (bNAbs) to prevent and treat HIV infection support the clinical utility and potential of bNAbs for prevention, postexposure prophylaxis, and treatment of acute and chronic infection. Observed and potential limitations of bNAbs from these recent studies include the selection of resistant viral populations, immunogenicity resulting in the development of antidrug (Ab) responses, and the potentially toxic elimination of reservoir cells in regeneration-limited tissues. Here, we review opportunities to improve the clinical utility of HIV Abs to address these challenges and further accomplish functional targets for anti-HIV Ab therapy at various stages of exposure/infection. Before exposure, bNAbs’ ability to serve as prophylaxis by neutralization may be improved by increasing serum half-life to necessitate less frequent administration, delivering genes for durable in vivo expression, and targeting bNAbs to sites of exposure. After exposure and/or in the setting of acute infection, bNAb use to prevent/reduce viral reservoir establishment and spread may be enhanced by increasing the potency with which autologous adaptive immune responses are stimulated, clearing acutely infected cells, and preventing cell–cell transmission of virus. In the setting of chronic infection, bNAbs may better mediate viral remission or “cure” in combination with antiretroviral therapy and/or latency reversing agents, by targeting additional markers of tissue reservoirs or infected cell types, or by serving as targeting moieties in engineered cell therapy. While the clinical use of HIV Abs has never been closer, remaining studies to precisely define, model, and understand the complex roles and dynamics of HIV Abs and viral evolution in the context of the human immune system and anatomical compartmentalization will be critical to both optimize their clinical use in combination with existing agents and define further strategies with which to enhance their clinical safety and efficacy. PMID:29234320

A polyvalent Clade B virus-like particle HIV vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus Infection in macaques and primes for virus-amplified immunity.

PubMed

Ross, Ted M; Pereira, Lara E; Luckay, Amara; McNicholl, Janet M; García-Lerma, J Gerardo; Heneine, Walid; Eugene, Hermancia S; Pierce-Paul, Brooke R; Zhang, Jining; Hendry, R Michael; Smith, James M

2014-11-01

Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown only partial protection from HIV-1 infection in human trials. Oral Truvada (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not been evaluated in humans. We determined the efficacy of combining a DNA/virus-like particle (VLP) vaccine with partially effective intermittent PrEP in Indian rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at weeks 0 and 4), followed by intramuscular and intranasal inoculations of homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were infected after a median of four exposures; the mean peak plasma viral load (VL) was 3.9×10(7) vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one infected CBP RM had a reduced peak VL of 8.8×10(5) copies/ml. SHIV exposures during PrEP amplified Gag and Env antibody titers in protected RM. These results suggest that combining oral PrEP with HIV vaccines could enhance protection against HIV-1 infection.

Sources of HIV infection among men having sex with men and implications for prevention ✻

PubMed Central

Ratmann, O.; van Sighem, A.; Bezemer, D.; Gavryushkina, A.; Jurriaans, S.; Wensing, A.; de Wolf, F.; Reiss, P.; Fraser, C.

2016-01-01

New HIV diagnoses among men having sex with men (MSM) have not decreased appreciably in most countries, even though care and prevention services have been scaled up substantially in the past twenty years. To maximize the impact of prevention strategies, it is crucial to quantify the sources of transmission at the population level. We used viral sequence and clinical patient data from one of Europe’s nation-wide cohort studies to estimate probable sources of transmission for 617 recently infected MSM. 71% of transmissions were from undiagnosed men, 6% from men who had initiated antiretroviral therapy (ART), 1% from men with no contact to care for at least 18 months, and 43% from those in their first year of infection. The lack of substantial reductions in incidence amongst Dutch MSM is not a result of ineffective ART provision or inadequate retention in care. In counterfactual modeling scenarios, 19% of these past cases could have been averted with current annual testing coverage and immediate ART to those testing positive. 66% of these cases could have been averted with available antiretrovirals (immediate ART provided to all MSM testing positive, and pre-exposure antiretroviral prophylaxis taken by half of all who test negative for HIV), but only if half of all men at risk of transmission had tested annually. With increasing sequence coverage, molecular epidemiological analyses can be a key tool to direct HIV prevention strategies to the predominant sources of infection, and help send HIV epidemics amongst MSM into a decisive decline. PMID:26738795

Where to deploy pre-exposure prophylaxis (PrEP) in sub-Saharan Africa?

PubMed

Verguet, Stéphane; Stalcup, Meg; Walsh, Julia A

2013-12-01

Two randomised controlled trials showed that pre-exposure prophylaxis (PrEP) reduces HIV transmission between heterosexual men and women. We model the potential impact on transmission and cost-effectiveness of providing PrEP in sub-Saharan Africa. We use a deterministic, compartmental model of HIV transmission to evaluate the potential of a 5-year PrEP intervention targeting the adult population of 42 sub-Saharan African countries. We examine the incremental impact of adding PrEP at pre-existing levels of male circumcision and antiretroviral therapy (ART). The base case assumes efficacy of 68%; adherence at 80%; country coverage at 10% of the HIV-uninfected adult population; and annual costs of PrEP and ART at US$200 and US$880 per person, respectively. After 5 years, 390,000 HIV infections (95% UR 190,000 to 630,000) would be prevented, 24% of these in South Africa. HIV infections averted per 100 000 people (adult) would range from 500 in Lesotho to 10 in Somalia. Incremental cost-effectiveness would be US$5800/disability-adjusted life year (DALY) (95% UR 3100 to 13500). Cost-effectiveness would range from US$500/DALY in Lesotho to US$44 600/DALY in Eritrea. In a general adult population, PrEP is a high-cost intervention which will have maximum impact and be cost-effective only in countries that have high levels of HIV burden and low levels of male circumcision in the population. Hence, PrEP will likely be most effective in Southern Africa as a targeted intervention added to existing strategies to control the HIV pandemic.

HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study.

PubMed

Colby, Donn; Srithanaviboonchai, Kriengkrai; Vanichseni, Suphak; Ongwandee, Sumet; Phanuphak, Nittaya; Martin, Michael; Choopanya, Kachit; Chariyalertsak, Suwat; van Griensven, Frits

2015-01-01

Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization as an effective method of HIV prevention for individuals at risk for infection. In this paper, we describe the unique role that Thailand has played in the global effort to combat the HIV epidemic, including its role in proving the efficacy of PrEP, and discuss the opportunities and challenges of implementing PrEP in a middle-income country. Thailand was one of the first countries in the world to successfully reverse a generalized HIV epidemic. Despite this early success, HIV prevalence has remained high among people who inject drugs and has surged among men who have sex with men (MSM) and transgender women (TGW). Two pivotal trials that showed that the use of oral antiretroviral medication as PrEP can reduce HIV transmission were conducted partially or entirely at Thai sites. Demonstration projects of PrEP, as well as clinical trials of alternative PrEP regimens, began or will begin in 2014-2015 in Thailand and will provide additional data and experience on how to best implement PrEP for high-risk individuals in the community. Financing of drug costs, the need for routine laboratory monitoring and lack of awareness about PrEP among at-risk groups all present challenges to the wider implementation of PrEP for HIV prevention in Thailand. Although significant challenges to wider use remain, PrEP holds promise as a safe and highly effective method to be used as part of a combined HIV prevention strategy for MSM and TGW in Thailand.

Mathematical modeling of HIV prevention measures including pre-exposure prophylaxis on HIV incidence in South Korea.

PubMed

Kim, Sun Bean; Yoon, Myoungho; Ku, Nam Su; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Kim, Changsoo; Kwon, Hee-Dae; Lee, Jeehyun; Smith, Davey M; Choi, Jun Yong

2014-01-01

Multiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation. We constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures. Overall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together. This model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM.

Cultural conundrums: the ethics of epidemiology and the problems of population in implementing pre-exposure prophylaxis.

PubMed

Fiereck, Kirk

2015-04-01

The impending implementation of pre-exposure prophylaxis (PrEP) has prompted complicated bioethical and public health ethics concerns regarding the moral distribution of antiretroviral medications (ARVs) to ostensibly healthy populations as a form of HIV prevention when millions of HIV-positive people still lack access to ARVs globally. This manuscript argues that these questions are, in part, concerns over the ethics of the knowledge production practices of epidemiology. Questions of distribution, and their attendant cost-benefit calculations, will rely on a number of presupposed, and therefore, normatively cultural assumptions within the science of epidemiology specifically regarding the ability of epidemiologic surveillance to produce accurate maps of HIV throughout national populations. Specifically, ethical questions around PrEP will focus on who should receive ARVs given the fact that global demand will far exceed supply. Given that sexual transmission is one of the main modes of HIV transmission, these questions of 'who' are inextricably linked to knowledge about sexual personhood. As a result, the ethics of epidemiology, and how the epidemiology of HIV in particular conceives, classifies and constructs sexual populations will become a critical point of reflection and contestation for bioethicists, health activists, physicians, nurses, and researchers in the multi-disciplinary field of global health. This paper examines how cultural conundrums within the fields of bioethics and public health ethics are directly implicated within the ethics of PrEP, by analyzing the problems of population inaugurated by the construction of the men who have sex with men (MSM) epidemiologic category in the specific national context of South Africa. © 2013 John Wiley & Sons Ltd.

Cultural Conundrums: The Ethics of Epidemiology and the Problems of Population in Implementing Pre-Exposure Prophylaxis

PubMed Central

2013-01-01

The impending implementation of pre-exposure prophylaxis (PrEP) has prompted complicated bioethical and public health ethics concerns regarding the moral distribution of antiretroviral medications (ARVs) to ostensibly healthy populations as a form of HIV prevention when millions of HIV-positive people still lack access to ARVs globally. This manuscript argues that these questions are, in part, concerns over the ethics of epidemiological science and knowledge production practices. Questions of distribution, and their attendant cost-benefit calculations, will rely on a number of presupposed, and therefore, normatively cultural assumptions within the science of epidemiology specifically regarding the ability of epidemiological surveillance to produce accurate maps of HIV throughout national populations. Specifically, ethical questions around PrEP will focus on who should receive ARVs given the fact that global demand will far exceed supply. Given that sexual transmission is one of the main modes of HIV transmission, these questions of “who” are inextricably linked to knowledge about sex, gender and sexuality. As a result, the ethics of epidemiology, and how the epidemiology of HIV in particular conceives, classifies and constructs sexual populations will become a critical point of reflection and contestation for bioethicists, health activists, physicians, nurses, and researchers in the medical humanities and biomedicine. This paper examines how cultural conundrums within the fields of bio- and public health ethics are directly implicated within the ethics of PrEP, by analyzing the problems of population inaugurated by the construction of the men who have sex with men (MSM) epidemiological category in the specific national context of South Africa. PMID:24373050

Mathematical Modeling of HIV Prevention Measures Including Pre-Exposure Prophylaxis on HIV Incidence in South Korea

PubMed Central

Kim, Sun Bean; Yoon, Myoungho; Ku, Nam Su; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Kim, Changsoo; Kwon, Hee-Dae; Lee, Jeehyun; Smith, Davey M.; Choi, Jun Yong

2014-01-01

Background Multiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation. Methods We constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures. Results Overall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together. Conclusions This model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM. PMID:24662776

Experiences Using Pre-Exposure Prophylaxis for Safer Conception Among HIV Serodiscordant Heterosexual Couples in the United States.

PubMed

Bazzi, Angela R; Leech, Ashley A; Biancarelli, Dea L; Sullivan, Meg; Drainoni, Mari-Lynn

2017-08-01

Antiretroviral pre-exposure prophylaxis (PrEP) is a promising HIV prevention strategy for HIV serodiscordant couples (HIV-infected male, uninfected female) seeking safer conception. However, most research on PrEP for safer conception has focused on couples in sub-Saharan Africa; little is known about the perspectives or experiences of heterosexual couples in the United States. We conducted qualitative interviews with six couples (six women and five of their male partners) receiving PrEP for conception services at an urban safety net hospital in the US Northeast. In-depth interview guides explored couple relationships and contextual factors and attitudes, perceptions, and decision-making processes surrounding PrEP for safer conception. Thematic analyses focused on identifying the following emergent themes. We found that couple relationships were situated within broader social and cultural contexts of immigration, family, and community that shaped their experiences with HIV and serodiscordant relationship status. Despite strong partner support within relationships, HIV stigma and disapproval of serodiscordant relationships contributed to couples' feelings of social isolation and subsequent aspirations to have "normal" families. By enabling "natural" conception through condomless sex, PrEP for safer conception provided a sense of enhanced relationship intimacy. Couples called for increasing public awareness of PrEP through positive messaging as a way to combat HIV stigma. Findings suggest that relationship dynamics and broader social contexts appear to shape HIV serodiscordant couples' fertility desires and motivations to use PrEP. However, increased public awareness of PrEP for safer conception may be needed to combat HIV stigma at the community level.

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions

PubMed Central

McNicholl, Janet M.

2016-01-01

ABSTRACT Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention. PMID:27679928

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

PubMed

McNicholl, Janet M

2016-12-01

Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

Timely antiretroviral prophylaxis during pregnancy effectively reduces HIV mother-to-child transmission in eight counties in China: a prospective study during 2004-2011.

PubMed

Wang, Qian; Wang, Linhong; Fang, Liwen; Wang, Ailing; Jin, Xi; Wang, Fang; Wang, Xiaoyan; Qiao, Yaping; Sullivan, Sheena G; Rutherford, Shannon; Zhang, Lei

2016-10-10

This study investigates the improvement of the prevention of mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) in China during 2004-2011. A clinic-based prospective study was conducted among HIV-positive pregnant women and their children in eight counties across China. Associated factors of mother-to-child transmission were analyzed using regression analysis. A total of 1,387 HIV+ pregnant women and 1,377 HIV-exposed infants were enrolled. The proportion of pregnant women who received HIV testing increased significantly from 45.1% to 98.9% during 2004-2011. Among whom, the proportion that received antiretroviral (ARV) prophylaxis increased from 61% to 96%, and the corresponding coverage in children increased from 85% to 97% during the same period. In contrast, single-dose nevirapine treatment during delivery declined substantially from 97.9% to 12.7%. Vertical transmission of HIV declined from 11.1% (95% confidence interval [CI]: 5.7-23.3%) in 2004 to 1.2% (95% CI: 0.1-5.8%) in 2011. Women who had a vaginal delivery (compared to emergency caesarian section (odds ratio [OR] = 0.46; 0.23-0.96)) and mothers on multi-ARVs (OR = 0.11; 0.04-0.29) were less likely to transmit HIV to their newborns. Increasing HIV screening enabled timely HIV care and prophylaxis to reduce vertical transmission of HIV. Early and consistent treatment with multi-ARVs during pregnancy is vital for PMTCT.

Recent developments in the understanding and use of anthrax vaccine adsorbed: achieving more with less.

PubMed

Schiffer, Jarad M; McNeil, Michael M; Quinn, Conrad P

2016-09-01

Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine's PEP application.

Issues of human rabies immunoglobulin and vaccine: policy versus practice.

PubMed

Folb, Jonathan E; Cooke, Richard P D

2007-03-01

A retrospective audit was conducted of all issues of rabies vaccine or human rabies immunoglobulin (HRIG) from the Clinical Microbiology Department at University Hospital Aintree for post-exposure prophylaxis. The appropriateness of management was reviewed by a blinded panel, which used guidelines issued by the Health Protection Agency (HPA) as a standard. Thirty-six enquiries, on average 9 days following exposure, led to issues of HRIG, rabies vaccine or both. Dog bites accounted for the majority of incidents. In no cases was the biting animal recorded as having been observed for signs of rabies. Management was judged to have been inappropriate in 9 cases, and documentation was judged to have been unsatisfactory in 13 cases. This study has highlighted several areas of ambiguity in the current guidelines, and a number of deficiencies in the information prompted by the standardized proformas used to deal with post-exposure queries.

High Rates of Baseline Drug Resistance and Virologic Failure Among ART-naive HIV-infected Children in Mali.

PubMed

Crowell, Claudia S; Maiga, Almoustapha I; Sylla, Mariam; Taiwo, Babafemi; Kone, Niaboula; Oron, Assaf P; Murphy, Robert L; Marcelin, Anne-Geneviève; Traore, Ban; Fofana, Djeneba B; Peytavin, Gilles; Chadwick, Ellen G

2017-11-01

Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children <10 years of age initiating ART in Mali. Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.

Dog bites in Bosnia.

PubMed Central

Croft, A; Archer, R

1997-01-01

BACKGROUND: Rabies is a zoonosis that remains endemic in most parts of the world. Primary care physicians are in the first line of defence against the disease. An increasing number of British practitioners and medical students are being exposed to the dangers of rabies through humanitarian work on overseas attachments. Rabies is enzootic throughout Bosnia-Herzegovina and presents a hazard to the multinational troops currently deployed there. AIM: To describe the British Army's experience of animal bites and rabies prevention in Bosnia during the first six months of its current peace enforcement mission, and to make general recommendations on the good management of any rabies hazard at primary care level and under field conditions. METHODS: Routine data from the Army's epidemiological database (ARRC 97) were reviewed, and theatre issues of rabies vaccine and immune globulin were used as a proxy measure for administered post-exposure prophylaxis. RESULTS: A total of 62 animal bites were reported in British troops between December 1995 and May 1996, of which 28 were unprovoked bites and resulted in the administration of a course of rabies vaccine. Ten of these were severe bites and rabies immune globulin (RIG) was administered in addition. The total cost of rabies post-exposure prophylaxis was US$6914.00. CONCLUSION: The prevention of rabies has major human and resource implications, and primary care staff involved in rabies post-exposure management need to be well supported in their clinical decision-making. Rabies protocols should be clear and unambiguous. The effective medical surveillance of military or humanitarian missions in rabies-enzootic areas must include the prompt reporting of animal bites. The predeployment training of medical teams should include an up-to-date assessment of the local rabies threat. PMID:9281871

Dosing antibiotic prophylaxis during cardiopulmonary bypass-a higher level of complexity? A structured review.

PubMed

Paruk, Fathima; Sime, Fekade B; Lipman, Jeffrey; Roberts, Jason A

2017-04-01

In highly invasive procedures such as open heart surgery, the risk of post-operative infection is particularly high due to exposure of the surgical field to multiple foreign devices. Adequate antibiotic prophylaxis is an essential intervention to minimise post-operative morbidity and mortality. However, there is a lack of clear understanding on the adequacy of traditional prophylactic dosing regimens, which are rarely supported by data. The aim of this structured review is to describe the relevant pharmacokinetic/pharmacodynamic (PK/PD) considerations for optimal antibiotic prophylaxis for major cardiac surgery including cardiopulmonary bypass (CPB). A structured review of the relevant published literature was performed and 45 relevant studies describing antibiotic pharmacokinetics in patients receiving extracorporeal CPB as part of major cardiac surgery were identified. Some of the studies suggested marked PK alterations in the peri-operative period with increases in volume of distribution (V d ) by up to 58% and altered drug clearances of up to 20%. Mechanisms proposed as causing the PK changes included haemodilution, hypothermia, retention of the antibiotic within the extracorporeal circuit, altered physiology related to a systemic inflammatory response, and maldistribution of blood flow. Of note, some studies reported no or minimal impact of the CPB procedure on antibiotic pharmacokinetics. Given the inconsistent data, ongoing research should focus on clarifying the influence of CPB procedure and related clinical covariates on the pharmacokinetics of different antibiotics during cardiac surgery. Traditional prophylactic dosing regimens may need to be re-assessed to ensure sufficient drug exposures that will minimise the risk of surgical site infections. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians.

PubMed

Palummieri, Antonio; De Carli, Gabriella; Rosenthal, Éric; Cacoub, Patrice; Mussini, Cristina; Puro, Vincenzo

2017-11-28

Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices.

"Since both of us are using antiretrovirals, we have been supportive to each other": facilitators and barriers of pre-exposure prophylaxis use in heterosexual HIV serodiscordant couples in Kisumu, Kenya.

PubMed

Patel, Rena C; Stanford-Moore, Gaelen; Odoyo, Josephine; Pyra, Maria; Wakhungu, Imeldah; Anand, Keerthana; Bukusi, Elizabeth A; Baeten, Jared M; Brown, Joelle M

2016-01-01

Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful rollout of PrEP among HIV serodiscordant couples in Kenya and other areas in sub-Saharan Africa, thereby reducing sexual transmission of HIV. Further research focused on how best to provide counselling on combination HIV prevention tools in the context of PrEP use is a crucial next step to delivering PrEP.

Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

PubMed

Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-09-06

CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

Hot News: HIV Epidemics - Current Burden and Future Prospects.

PubMed

de Mendoza, Carmen

2017-01-01

The latest estimate from the WHO is of nearly 37 million people living with HIV worldwide by the end of 2016. Roughly 20 million are receiving antiretroviral therapy. Despite this progress in diagnosis and treatment, nearly 2 million new HIV infections continue to occur annually. Whereas men having sex with men (MSM) represent the major risk population for incident cases in North America and the European Union, infection of heterosexual women is the major group in Sub-Saharan Africa. Injection drug use is a leading mechanism of HIV acquisition in Asia, including Russia and the former Soviet republics. Given that HIV cannot be eradicated from infected persons, antiretroviral therapy prescribed as early as possible and forever has become the paradigm to both avoid clinical progression and prevent further transmissions. No protective vaccines are on the horizon, at least within a 5-year view. New genetic strategies (i.e., using CRISPR) that pursue elimination or lethal dysfunction of the HIV provirus hidden in human cell reservoirs have renewed the interest for HIV cure. Ultimately, they represent the most serious hope for controlling and eliminating the HIV pandemics. In the mean time, the benefit of antiretrovirals is being extended using oral drugs at demand in uninfected persons at risk as pre-exposure prophylaxis (PrEP). However, accompanying declines in condom use and increases in sexually transmitted infections are a major concern promoting PrEP. Alerts on rising syphilis and gonorrhea, and outbreaks of acute hepatitis C and now hepatitis A reflect the lack of adequate education, especially among MSM. Altogether, the updated figures from WHO and UNAIDS on the current status of the HIV epidemics suggest that a plateau may have been reached. Thereby, major efforts will be further required to envision a HIV/AIDS-free world. Major gaps still exist in access to antiretroviral therapy, diagnosis of people unaware of their infection, education on risk behaviors and interventions for preventing new HIV infections.

Given Resource Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention

PubMed Central

Macklin, Ruth; Cowan, Ethan

2013-01-01

Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies preexposure prophylaxis and treatment as prevention—use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention. PMID:22778343

Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney recipients on early and late post-transplantation lymphoproliferative disorder onset: a retrospective cohort study.

PubMed

Ville, Simon; Imbert-Marcille, Berthe-Marie; Coste-Burel, Marianne; Garandeau, Claire; Meurette, Aurélie; Cantarovitch, Diego; Giral, Magali; Hourmant, Maryvonne; Blancho, Gilles; Dantal, Jacques

2018-05-01

Post-transplantation lymphoproliferative disorder (PTLD) pathogenesis is related to EBV infection. Mismatch with the donor (EBV D+/R-) is the main risk factor for both early PTLD (<1 year post-transplantation) and late (>1 year). In these at-risk patients, the role of antiviral prophylaxis for preventing PTLD remains controversial. We analyzed the impact of antiviral drugs given to prevent CMV disease in a monocentric retrospective cohort of 73 adult kidney or kidney-pancreas EBV-seronegative recipients, transplanted between 01/01/2000 and 01/01/2016. Thirty-seven (50.7%, prophylaxis group) received (val-)aciclovir or (val-)ganciclovir for 3-6 months and 36 (49.3%, no-prophylaxis group) received no-prophylaxis. Mean follow-up was 69 ± 7.2 months in the prophylaxis group and 91 ± 10.3 months in the no-prophylaxis group. Monitoring of EBV PCR revealed that prophylaxis delayed primary infection at 100 days (43% vs. 84%, P = 0.02). Early PTLD incidence was not different between groups (4/37 vs. 4/36, P = 0.99). Concerning late events, EBV-related neoplasia incidence was significantly lower in treated patients among whom no cases were observed, while in the no-prophylaxis group 6 cases were reported (P = 0.02). Despite a weak level of evidence our study suggests that antiviral prophylaxis could prevent late onset PTLD. © 2017 Steunstichting ESOT.

Should nevirapine be used to prevent mother-to-child transmission of HIV among women of unknown serostatus?

PubMed Central

Sint, Tin Tin; Dabis, François; Kamenga, Claude; Shaffer, Nathan; de Zoysa, Isabelle F.

2005-01-01

At present, HIV testing and counselling during pregnancy represent the key entry point for women to learn their serostatus and for them to access, if they are HIV-positive, specific interventions to reduce mother-to-child transmission (MTCT) of HIV. However, the provision and uptake of testing and counselling services are inadequate, and many pregnant women in countries most affected by the HIV/AIDS epidemic remain unaware of their HIV status. The offer of single-dose nevirapine prophylaxis to women whose HIV status is unknown at the time of delivery has been proposed to circumvent these problems in high-prevalence settings. The potential advantages and disadvantages of three different programme approaches are considered: targeted programmes in which antiretroviral drugs are offered only to women who are known to be HIV-positive; combined programmes in which nevirapine prophylaxis is offered to women whose serostatus remains unknown at the time of delivery despite targeted programme inputs; and universal nevirapine prophylaxis programmes in which HIV testing and counselling are not available and all pregnant women, regardless of their serostatus, are offered nevirapine prophylaxis. PMID:15798847

Offering pre-exposure prophylaxis for HIV prevention to pregnant and postpartum women: a clinical approach

PubMed Central

Seidman, Dominika L; Weber, Shannon; Cohan, Deborah

2017-01-01

Abstract Introduction: HIV prevention during pregnancy and lactation is critical for both maternal and child health. Pregnancy provides a critical opportunity for clinicians to elicit women’s vulnerabilities to HIV and offer HIV testing, treatment and referral and/or comprehensive HIV prevention options for the current pregnancy, the postpartum period and safer conception options for future pregnancies. In this commentary, we review the safety of oral pre-exposure prophylaxis with tenofovir/emtricitabine in pregnant and lactating women and suggest opportunities to identify pregnant and postpartum women at substantial risk of HIV. We then describe a clinical approach to caring for women who both choose and decline pre-exposure prophylaxis during pregnancy and postpartum, highlighting areas for future research. Discussion: Evidence suggests that pre-exposure prophylaxis with tenofovir/emtricitabine is safe in pregnancy and lactation. Identifying women vulnerable to HIV and eligible for pre-exposure prophylaxis is challenging in light of the myriad of individual, community, and structural forces impacting HIV acquisition. Validated risk calculators exist for specific populations but have not been used to screen and offer HIV prevention methods. Partner testing and engagement of men living with HIV are additional means of reaching at-risk women. However, women’s vulnerabilities to HIV change over time. Combining screening for HIV vulnerability with HIV and/or STI testing at standard intervals during pregnancy is a practical way to prompt providers to incorporate HIV screening and prevention counselling. We suggest using shared decision-making to offer women pre-exposure prophylaxis as one of multiple HIV prevention strategies during pregnancy and postpartum, facilitating open conversations about HIV vulnerabilities, preferences about HIV prevention strategies, and choosing a method that best meets the needs of each woman. Conclusion: Growing evidence suggests that pre-exposure prophylaxis with tenofovir/emtricitabine during pregnancy and lactation is safe and effective. Shared decision-making provides one approach to identify at-risk women and offers pre-exposure prophylaxis but requires implementation research in diverse clinical settings. Including pregnant and breastfeeding women in future HIV prevention research is critical for the creation of evidence-driven public health policies and clinical guidelines. PMID:28361503

Offering pre-exposure prophylaxis for HIV prevention to pregnant and postpartum women: a clinical approach.

PubMed

Seidman, Dominika L; Weber, Shannon; Cohan, Deborah

2017-03-08

HIV prevention during pregnancy and lactation is critical for both maternal and child health. Pregnancy provides a critical opportunity for clinicians to elicit women's vulnerabilities to HIV and offer HIV testing, treatment and referral and/or comprehensive HIV prevention options for the current pregnancy, the postpartum period and safer conception options for future pregnancies. In this commentary, we review the safety of oral pre-exposure prophylaxis with tenofovir/emtricitabine in pregnant and lactating women and suggest opportunities to identify pregnant and postpartum women at substantial risk of HIV. We then describe a clinical approach to caring for women who both choose and decline pre-exposure prophylaxis during pregnancy and postpartum, highlighting areas for future research. Evidence suggests that pre-exposure prophylaxis with tenofovir/emtricitabine is safe in pregnancy and lactation. Identifying women vulnerable to HIV and eligible for pre-exposure prophylaxis is challenging in light of the myriad of individual, community, and structural forces impacting HIV acquisition. Validated risk calculators exist for specific populations but have not been used to screen and offer HIV prevention methods. Partner testing and engagement of men living with HIV are additional means of reaching at-risk women. However, women's vulnerabilities to HIV change over time. Combining screening for HIV vulnerability with HIV and/or STI testing at standard intervals during pregnancy is a practical way to prompt providers to incorporate HIV screening and prevention counselling. We suggest using shared decision-making to offer women pre-exposure prophylaxis as one of multiple HIV prevention strategies during pregnancy and postpartum, facilitating open conversations about HIV vulnerabilities, preferences about HIV prevention strategies, and choosing a method that best meets the needs of each woman. Growing evidence suggests that pre-exposure prophylaxis with tenofovir/emtricitabine during pregnancy and lactation is safe and effective. Shared decision-making provides one approach to identify at-risk women and offers pre-exposure prophylaxis but requires implementation research in diverse clinical settings. Including pregnant and breastfeeding women in future HIV prevention research is critical for the creation of evidence-driven public health policies and clinical guidelines.

Assessment of management policies and practices for occupational exposure to bloodborne pathogens in dialysis facilities.

PubMed

Mbaeyi, Chukwuma; Panlilio, Adelisa L; Hobbs, Cynthia; Patel, Priti R; Kuhar, David T

2012-10-01

Occupational exposure management is an important element in preventing the transmission of bloodborne pathogens in health care settings. In 2008, the US Centers for Disease Control and Prevention conducted a survey to assess procedures for managing occupational bloodborne pathogen exposures in outpatient dialysis facilities in the United States. A cross-sectional survey of randomly selected outpatient dialysis facilities. 339 outpatient dialysis facilities drawn from the 2006 US end-stage renal disease database. Hospital affiliation (free-standing vs hospital-based facilities), profit status (for-profit vs not-for-profit facilities), and number of health care personnel (≥100 vs <100 health care personnel). Exposures to hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV); provision of HBV and HIV postexposure prophylaxis. We calculated the proportion of facilities reporting occupational bloodborne pathogen exposures and offering occupational exposure management services. We analyzed bloodborne pathogen exposures and provision of postexposure prophylaxis by facility type. Nearly all respondents (99.7%) had written policies and 95% provided occupational exposure management services to health care personnel during the daytime on weekdays, but services were provided infrequently during other periods of the week. Approximately 10%-15% of facilities reported having HIV, HBV, or HCV exposures in health care personnel in the 12 months prior to the survey, but inconsistencies were noted in procedures for managing such exposures. Despite 86% of facilities providing HIV prophylaxis for exposed health care personnel, only 37% designated a primary HIV postexposure prophylaxis regimen. For-profit and free-standing facilities reported fewer exposures, but did not as reliably offer HBV prophylaxis or have a primary HIV postexposure prophylaxis regimen relative to not-for-profit and hospital-based facilities. The survey response rate was low (37%) and familiarity of individuals completing the survey with facility policies or national guidelines could not be ascertained. Significant improvements are required in the implementation of guidelines for managing occupational exposures to bloodborne pathogens in outpatient dialysis facilities. Published by Elsevier Inc.

Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

PubMed Central

Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

2015-01-01

Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

Awareness and knowledge of human immunodeficiency virus post exposure prophylaxis among Nigerian Family Physicians.

PubMed

Agaba, Patricia A; Agaba, Emmanuel I; Ocheke, Amaka N; Daniyam, Comfort A; Akanbi, Maxwell O; Okeke, Edith N

2012-07-01

To determine the level of awareness and knowledge of HIV postexposure prophylaxis (HIV PEP) and determinants of adequate knowledge among Family Physicians in Nigeria. This was a cross-sectional questionnaire-based survey conducted among 175 Family Physicians at two national conferences. Majority (97.7%) of the respondents was aware of the concept of HIV PEP and 99.4% believed it was effective in preventing HIV transmission. Over two third of our respondents had been exposed to NSI; however, less than 25% of those exposed received PEP. There was high level of knowledge of the various high-risk body fluids as well as types of high-risk exposures. 93.9% of our respondents knew that HIV PEP should commence within 1 h of exposure, 83.3% knew the correct duration of HIV PEP, but only 57.0% knew the ideal PEP regimen for high-risk exposures. The total mean score for our respondents was 17.8±2.9 with 79.4% having an adequate score. Being a junior doctor and male sex were associated with adequate knowledge. This study shows that despite high levels of awareness and knowledge of HIV PEP, access to its use among family physicians in Nigeria is still sub-optimal.

Pre-Exposure Prophylaxis (PrEP)

MedlinePlus

... VA – HIV Pre-Exposure Prophylaxis HIV.gov on Twitter 22 hours 47 min ago. HIV.gov @HIVGov # ... routine. #HIVTestingDay Reply Retweet Favorite HIV.gov on Twitter Search Find HIV Testing Sites & Care Services Connect ...

A Missed Opportunity for U.S. Perinatal Human Immunodeficiency Virus Elimination: Pre-exposure Prophylaxis During Pregnancy.

PubMed

Fruhauf, Timothee; Coleman, Jenell S

2017-10-01

To estimate the proportion of women at increased risk of sexual human immunodeficiency virus (HIV) acquisition during pregnancy in a high HIV incidence urban setting to identify those who may be eligible for pre-exposure prophylaxis. We conducted a retrospective cohort study of women who received prenatal care at a large academic center in 2012. Univariable analyses and multiple logistic regression models were built to identify correlates for pre-exposure prophylaxis eligibility. Among 1,637 pregnant women, mean age was 27.6 years (SD 6.3), 59.7% were African American, and 56.0% were single. Based on the Centers for Disease Control and Prevention's guidelines, more than 10% of women were at increased risk for HIV acquisition during pregnancy and eligible for pre-exposure prophylaxis. Younger [adjusted odds ratio (OR) 0.9/1-year increase, 95% CI 0.8-0.9], single (adjusted OR 2.4, 95% CI 1.2-4.8), African American women (adjusted OR 3.3, 95% CI 1.6-6.7) with higher parity (adjusted OR 1.3/one-child increase, 95% CI 1.1-1.5), and who smoked regularly during pregnancy (adjusted OR 1.8, 95% CI 1.0-3.0) had greater odds of being eligible for pre-exposure prophylaxis at any time during pregnancy. Pregnancy is a vulnerable period during which some heterosexual women in urban settings have a high risk for HIV acquisition and stand to benefit from pre-exposure prophylaxis.

Preventing Mother-to-Child Transmission of HIV in Resource-Limited Settings: The Elizabeth Glaser Pediatric AIDS Foundation Experience

PubMed Central

Sripipatana, Tabitha; Turner, Abigail Norris; Hoblitzelle, Chuck; Robinson, Joanna; Wilfert, Catherine

2009-01-01

Objectives. In September 1999, the Elizabeth Glaser Pediatric AIDS Foundation initiated a multicountry, service-based programmatic effort in the developing world to reduce perinatally acquired HIV infection. We review 6½ years of one of the world's largest programs for the prevention of mother-to-child transmission (PMTCT) of HIV. Methods. Each PMTCT facility records patient data in antenatal clinics and labor and delivery settings about counseling, testing, HIV status, and antiretroviral prophylaxis and submits the data to foundation staff. Results. More than 2.6 million women have accessed foundation-affiliated services through June 2006. Overall, 92.9% of women who received antenatal care or were eligible for PMTCT services in labor and delivery have been counseled, and 82.8% of those counseled accepted testing. Among women identified as HIV positive, 75.0% received antiretroviral prophylaxis (most a single dose of nevirapine), as did 45.6% of their infants. Conclusions. The foundation's experience has demonstrated that opt-out testing, supplying mothers with medication at time of diagnosis, and providing the infant dose early have measurably improved program efficiency. PMTCT should be viewed as an achievable paradigm and an essential part of the continuum of care. PMID:18703458

Needlestick and Sharps Injuries in Dermatologic Surgery: A Review of Preventative Techniques and Post-exposure Protocols

PubMed Central

Monroe, Holly; Orengo, Ida; Rosen, Theodore

2016-01-01

Background: Needlestickand sharps injuries are the leading causes of morbidity in the dermatologicfield. Among medical specialties, surgeons and dermatologists have the highest rates of needlestickand sharps injuries.The high rates of needlestickand sharps injuries in dermatology not only apply to physicians, but also to nurses, physician assistants, and technicians in the demnatologic field. Needlestickand sharps injuries are of great concern due to the monetary, opportunity, social, and emotional costs associated with their occurrence. Objective: A review of preventative techniques and post-exposure protocols for the majortypes of sharps injuries encountered in dermatologic practice. Design: The terms “needle-stick injuryT’sharps injuryTdermatologic surgery? “post-exposure prophylaxis,”and “health-care associated injury” were used in combinations to search the PubMed database. Relevant studies were reviewed for validity and included. Results The authors discuss the major types of sharps injuries that occur in the dermatologic surgery setting and summarize preventative techniques with respect to each type of sharps injury.The authors also summarize and discuss relevant post-exposure protocols in the event of a sharps injury. Conclusion: The adoption of the discussed methods, techniques, practices, and attire can result in the elimination of the vast majority of dermatologic sharps injuries. PMID:27847548

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

PubMed

Ryom, L; Boesecke, C; Gisler, V; Manzardo, C; Rockstroh, J K; Puoti, M; Furrer, H; Miro, J M; Gatell, J M; Pozniak, A; Behrens, G; Battegay, M; Lundgren, J D

2016-02-01

The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview. © 2015 British HIV Association.

HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study

PubMed Central

Colby, Donn; Srithanaviboonchai, Kriengkrai; Vanichseni, Suphak; Ongwandee, Sumet; Phanuphak, Nittaya; Martin, Michael; Choopanya, Kachit; Chariyalertsak, Suwat; van Griensven, Frits

2015-01-01

Introduction Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization as an effective method of HIV prevention for individuals at risk for infection. In this paper, we describe the unique role that Thailand has played in the global effort to combat the HIV epidemic, including its role in proving the efficacy of PrEP, and discuss the opportunities and challenges of implementing PrEP in a middle-income country. Discussion Thailand was one of the first countries in the world to successfully reverse a generalized HIV epidemic. Despite this early success, HIV prevalence has remained high among people who inject drugs and has surged among men who have sex with men (MSM) and transgender women (TGW). Two pivotal trials that showed that the use of oral antiretroviral medication as PrEP can reduce HIV transmission were conducted partially or entirely at Thai sites. Demonstration projects of PrEP, as well as clinical trials of alternative PrEP regimens, began or will begin in 2014–2015 in Thailand and will provide additional data and experience on how to best implement PrEP for high-risk individuals in the community. Financing of drug costs, the need for routine laboratory monitoring and lack of awareness about PrEP among at-risk groups all present challenges to the wider implementation of PrEP for HIV prevention in Thailand. Conclusions Although significant challenges to wider use remain, PrEP holds promise as a safe and highly effective method to be used as part of a combined HIV prevention strategy for MSM and TGW in Thailand. PMID:26198342

HIV testing, care, and treatment experiences among the steady male partners of female sex workers living with HIV in the Dominican Republic

PubMed Central

Fleming, Paul J.; Barrington, Clare; Perez, Martha; Donastorg, Yeycy; Kerrigan, Deanna

2016-01-01

Male steady partners of female sex workers (FSW) living with HIV represent a key population for treatment as prevention and/or pre-exposure prophylaxis (PrEP) interventions. This study uses data collected from male steady partners who were referred by FSW living with HIV participating in a multi-level HIV prevention and care intervention in Santo Domingo, Dominican Republic. We conducted a socio-behavioral survey and HIV-testing with all men (n=64) and 16 in-depth interviews with a sub-sample to obtain more depth. Thirty-five of the 64 participants were living with HIV; 27 were previously diagnosed and 8 were diagnosed during our study. As a result, 45% of men were members of a sero-discordant sexual partnerships. Of men with no previous HIV diagnosis (n=37), 15 had never been tested for HIV and 9 had not been tested in the past two years. Ninety-three percent of men previously diagnosed with HIV reported receiving HIV care in the past 6 months and 78% were taking anti-retrovirals. Low HIV testing was partly due to men not feeling at-risk for HIV, despite having an HIV-infected partner. Additionally, a lack of tailored care inhibited engagement in ARV treatment for those infected. HIV testing was low, highlighting a need for test-and-treat strategies. Men not living with HIV would benefit from regular testing and would be good candidates for pre-exposure prophylaxis. While almost all men who had been diagnosed with HIV were engaged in care and adherent to ART, future research should assess whether they are achieving optimal HIV outcomes for their health and prevention of ongoing transmission. PMID:27009379

Pre-exposure prophylaxis for HIV prevention in women: current perspectives

PubMed Central

Flash, Charlene A; Dale, Sannisha K; Krakower, Douglas S

2017-01-01

There are ~900,000 new HIV infections among women every year, representing nearly half of all new HIV infections globally. In the US, nearly one-fifth of all new HIV infections occur among women, and women from racial and ethnic minority communities experience disproportionately high rates of new HIV infections. Thus, there is a need to develop and implement effective HIV prevention strategies for women in the US and internationally, with a specific need to advance strategies in minority communities. Previous studies have demonstrated that oral HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral medications by HIV-uninfected persons to prevent HIV acquisition, can reduce HIV incidence among women who are adherent to PrEP. However, to date, awareness and uptake of PrEP among women have been very limited, suggesting a need for innovative strategies to increase the knowledge of and access to PrEP among women in diverse settings. This narrative review summarizes the efficacy and safety data of PrEP in women, discusses considerations related to medication adherence for women who use PrEP, and highlights behavioral, social, and structural barriers to maximize the effectiveness of PrEP in women. It also reviews novel modalities for PrEP in women which are being developed and tested, including topical formulations and long-acting injectable agents that may offer advantages as compared to oral PrEP and proposes a community-oriented, social networking framework to increase awareness of PrEP among women. If women are provided with access to PrEP and support to overcome social and structural barriers to adhere to PrEP, this prevention strategy holds great promise to impact the HIV epidemic among women in the US and globally. PMID:28615975

Values and Preferences on the Use of Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A Systematic Review of the Literature.

PubMed

Koechlin, Florence M; Fonner, Virginia A; Dalglish, Sarah L; O'Reilly, Kevin R; Baggaley, Rachel; Grant, Robert M; Rodolph, Michelle; Hodges-Mameletzis, Ioannis; Kennedy, Caitlin E

2017-05-01

Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.

Primary care clinicians' experiences prescribing HIV pre-exposure prophylaxis at a specialized community health centre in Boston: lessons from early adopters.

PubMed

Krakower, Douglas S; Maloney, Kevin M; Grasso, Chris; Melbourne, Katherine; Mayer, Kenneth H

2016-01-01

An estimated 1.2 million Americans have indications for using antiretroviral pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at-risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists. During January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics. Thirty-two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11-33). Most clinicians reported testing and risk-reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians' practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future. In a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale-up of this efficacious intervention.

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa

PubMed Central

Wheeler, Stephanie B.; Stranix-Chibanda, Lynda; Hosek, Sybil G.; Watts, D. Heather; Siberry, George K.; Spiegel, Hans M. L.; Stringer, Jeffrey S.; Chi, Benjamin H.

2016-01-01

Introduction: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. Methods: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. Results: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. Conclusions: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy. PMID:27355502

Evaluating the impact of prioritization of antiretroviral pre-exposure prophylaxis (PrEP) in New York City

PubMed Central

Kessler, Jason; Myers, Julie E.; Nucifora, Kimberly A.; Mensah, Nana; Toohey, Christopher; Khademi, Amin; Cutler, Blayne; Braithwaite, R. Scott

2015-01-01

Objective To compare the value and effectiveness of different prioritization strategies of pre-exposure prophylaxis (PrEP) in New York City (NYC). Design Mathematical modeling utilized as clinical trial is not feasible. Methods Using a model accounting for both sexual and parenteral transmission of HIV we compare different prioritization strategies (PPS) for PrEP to two scenarios—no PrEP and PrEP for all susceptible at-risk individuals. The PPS included PrEP for all MSM, only high-risk MSM, high-risk heterosexuals, and injection drug users, and all combinations of these four strategies. Outcomes included HIV infections averted, and incremental cost effectiveness (per-infection averted) ratios. Initial assumptions regarding PrEP included a 44% reduction in HIV transmission, 50% uptake in the prioritized population and an annual cost per person of $9,762. Sensitivity analyses on key parameters were conducted. Results Prioritization to all MSM results in a 19% reduction in new HIV infections. Compared to PrEP for all persons at-risk this PPS retains 79% of the preventative effect at 15% of the total cost. PrEP prioritized to only high-risk MSM results in a reduction in new HIV infections of 15%. This PPS retains 60% of the preventative effect at 6% of the total cost. There are diminishing returns when PrEP utilization is expanded beyond this group. Conclusions PrEP implementation is relatively cost-inefficient under our initial assumptions. Our results suggest that PrEP should first be promoted among MSM who are at particularly high-risk of HIV acquisition. Further expansion beyond this group may be cost-effective, but is unlikely to be cost-saving. PMID:25493594

Stigma and Conspiracy Beliefs Related to Pre-exposure Prophylaxis (PrEP) and Interest in Using PrEP Among Black and White Men and Transgender Women Who Have Sex with Men

PubMed Central

Kalichman, Seth C.; Price, Devon; Finneran, Stephanie; Allen, Aerielle; Maksut, Jessica

2018-01-01

The HIV/AIDS epidemic in the US continues to persist, in particular, among race, sexual orientation, and gender minority populations. Pre-exposure prophylaxis (PrEP), or using antiretroviral medications for HIV prevention, is an effective option, but uptake of PrEP has been slow. Sociocultural barriers to using PrEP have been largely underemphasized, yet have the potential to stall uptake and, therefore, warrant further understanding. In order to assess the relationships between potential barriers to PrEP (i.e., PrEP stigma and conspiracy beliefs), and interest in PrEP, Black men and transgender women who have sex with men (BMTW, N = 85) and White MTW (WMTW, N = 179) were surveyed at a gay pride event in 2015 in a large southeastern US city. Bivariate and multivariate logistic regression analyses were completed to examine factors associated with PrEP interest. Among the full sample, moderate levels of PrEP awareness (63%) and low levels of use (9%) were observed. Believing that PrEP is for people who are promiscuous (stigma belief) was strongly associated with lack of interest in using PrEP, and individuals who endorsed this belief were more likely to report sexual risk taking behavior. Conspiracy beliefs related to PrEP were reported among a large minority of the sample (42%) and were more frequently reported among BMTW than WMTW. Given the strong emphasis on the use of biomedical strategies for HIV prevention, addressing sociocultural barriers to PrEP access is urgently needed and failure to do so will weaken the potential benefits of biomedical prevention. PMID:28108878

Perceptions among Dutch men who have sex with men and their willingness to use rectal microbicides and oral pre-exposure prophylaxis to reduce HIV risk--a preliminary study.

PubMed

Marra, Elske; Hankins, Catherine A

2015-01-01

Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the Netherlands explored perceptions of MSM and their willingness to use oral PrEP and rectal microbicides (RM) if made available. Recruited through social media (Facebook and Twitter), 108 MSM completed online questionnaires. Seven of them consented to discuss the survey results in semi-structured interviews. Survey participants preferred a RM that could be applied before and after anal intercourse (60.8%) to daily oral PrEP (20.3%). This preference was based on anticipated user friendliness, hypothetically fewer expected adverse events, and perceptions that RM would be less likely to be confused with ARVs for treatment. Those who preferred oral PrEP had stronger beliefs in the effectiveness of pills, perceived its use as easy, and viewed not requiring sexual partner awareness as advantages. No predictive factors were found for the choice of one prevention method over the other. Although Dutch MSM perceive both oral and topical PrEP positively, many barriers exist to the introduction of these products in the Netherlands. These include lack of regulatory approval of oral PrEP, no proven efficacy as yet for RM, and strong HIV stigma within the MSM population. In-depth qualitative research is needed to further explore the perceptions of MSM to inform implementation of programmes should these HIV prevention methods become available.

WHO guidance grounded in a comprehensive approach to sexual and reproductive health and human rights: topical pre-exposure prophylaxis.

PubMed

Lusti-Narasimhan, Manjula; Khosla, Rajat; Baggaley, Rachel; Temmerman, Marleen; McGrory, Elizabeth; Farley, Tim

2014-01-01

Two new microbicide products based on topical (vaginal) application of antiretroviral drugs - 1% tenofovir gel and the dapivirine ring - are currently in late-stage clinical testing, and results on their safety and effectiveness are expected to become available in early 2015. WHO guidelines on the use of topical pre-exposure prophylaxis (topical PrEP) are important in order to ensure that these new prevention products are optimally used. Given that these new topical PrEP products are designed to be woman initiated and will likely be delivered in reproductive health settings, it is important to ensure that the guidance be framed in the context of comprehensive sexual and reproductive health and human rights. In addition to the safety and effectiveness data resulting from clinical trials, and the regulatory approval required for new products, the WHO normative guidelines on the use of topical PrEP will be essential for rapid roll-out in countries. Human rights standards and principles provide a framework for the provision of woman-initiated HIV prevention products. These include addressing issues related to the gender inequities which are linked to the provision of HIV-prevention, treatment and care for young girls and women. Effective programming for women and girls must therefore be based on understanding the local, social and community contexts of the AIDS epidemic in the country, and adapting HIV strategies and programmes accordingly. Such a framework therefore is needed not only to ensure optimal uptake of these new products by women and girls but also to address sociocultural barriers to women's and girls' access to these products.

Acceptability and preferences for safer conception HIV prevention strategies: A qualitative study

PubMed Central

Schwartz, Sheree; West, Nora; Phofa, Rebecca; Yende, Nompumelelo; Sanne, Ian; Bassett, Jean; Van Rie, Annelies

2016-01-01

Safer conception strategies to reduce HIV transmission risk include antiretroviral therapy (ART) for HIV-positive partners, pre-exposure prophylaxis (PrEP) for HIV-negative partners, condomless sex limited to fertile periods, and home-based self-insemination. Resistance to taking treatment or cultural concerns may limit uptake of strategies and intervention success. Understanding the acceptability and preferences between different approaches is important to optimize service delivery. Between February-July 2013, 42 adults (21 HIV-positive and 21 HIV-negative) receiving primary care at Witkoppen Health and Welfare Centre in Johannesburg, South Africa, participated in focus group discussions or in-depth interviews. Themes were analyzed using a grounded theory approach. Acceptability of antiretroviral-based (ARV) strategies varied. Concerns over side effects, ARV treatment duration, and beliefs that treatment is only for the sick were common barriers, however desperation for a child was noted as a facilitator for uptake. HIV-negative men and HIV-positive women had favorable attitudes towards self-insemination, though paternity and safety concerns were raised. Self-insemination was generally preferred over PrEP by HIV-negative men, and ARV-based strategies were preferred by couples with HIV-negative female partners, despite concerns raised about condomless sex while virally suppressed. Knowledge about the fertile window was low. A strong counselling component will be required for effective uptake and adherence to safer conception services. PMID:26384950

Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study

PubMed Central

Haberer, Jessica; Celum, Connie; Mugo, Nelly; Ware, Norma C.; Cohen, Craig R.; Tappero, Jordan W.; Kiarie, James; Ronald, Allan; Mujugira, Andrew; Tumwesigye, Elioda; Were, Edwin; Irungu, Elizabeth; Baeten, Jared M.

2016-01-01

Background: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP). Methods: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence. Results: Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0–35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away. Conclusions: Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated. PMID:27243900

Epidemiology and prophylaxis of rabies in humans in France: evaluation and perspectives of a twenty-five year surveillance programme.

PubMed

Rotivel, Y; Goudal, M; De Fanti, A Simons; Van Der Vliet, D

2008-01-01

The National Reference Centre for Rabies (NRC) was created at the Pasteur Institute after the fox epizootic reached the French territory. The missions of the NRC include, among others, the surveillance of rabies cases in humans and rabies post-exposure prophylaxis (PEP) treatments. The surveillance has been effective since 1982. A Bulletin on the Epidemiology and the Prophylaxis of Rabies in Humans in France is published every year. This Bulletin is now available on the Internet for Human Health and Veterinary national and local Authorities. Since 2005, data is collected with new software, Voozanoo, directly via the Internet. Twenty cases of rabies in humans have been reported since 1970. There were no indigenously acquired cases. The number of PEP treatments peaked in 1990, when the number of cases in the wild fauna was at its acme. Following the decrease of rabies cases in the wild fauna, PEP decreased by 60%. Nevertheless, about4,000 PEP treatments are still carried out. These patients have been exposed to bats or to rabid animals illegally introduced onto the French territory, or during a stay in rabies enzootic countries, or to unobservable animals. The study of this database leads to a number of conclusions: canine variants acquired directly in canine enzootic areas, that are translocated, or acquired through iatrogenic exposure, are responsible for the majority of cases; bats appear to be an increasing source of exposure; PEP surveillance is of utmost importance to monitor and to improve the quality of case management.

Women's decision-making and uptake of services to prevent mother-to-child HIV transmission in Zambia.

PubMed

Ford, Catherine; Chibwesha, Carla J; Winston, Jennifer; Jacobs, Choolwe; Lubeya, Mwansa Ketty; Musonda, Patrick; Stringer, Jeffrey S A; Chi, Benjamin H

2018-04-01

Women's empowerment is associated with engagement in some areas of healthcare, but its role in prevention of mother-to-child HIV transmission (PMTCT) services has not been previously considered. In this secondary analysis, we investigated the association of women's decision-making and uptake of health services for PMTCT. Using data from population-based household surveys, we included women who reported delivery in the 2-year period prior to the survey and were HIV-infected. We measured a woman's self-reported role in decision-making in her own healthcare, making of large purchases, schooling of children, and healthcare for children. For each domain, respondents were categorized as having an "active" or "no active" role. We investigated associations between decision-making and specific steps along the PMTCT cascade: uptake of maternal antiretroviral drugs, uptake of infant HIV prophylaxis, and infant HIV testing. We calculated unadjusted and adjusted odds ratios via logistic regression. From March to December 2011, 344 HIV-infected mothers were surveyed and 276 completed the relevant survey questions. Of these, 190 (69%) took antiretroviral drugs during pregnancy; 175 (64%) of their HIV-exposed infants received antiretroviral prophylaxis; and 160 (58%) had their infant tested for HIV. There was no association between decision-making and maternal or infant antiretroviral drug use. We observed a significant association between decision-making and infant HIV testing in univariate analyses (OR 1.56-1.85; p < 0.05); however, odds ratios for the decision-making indicators were no longer statistically significant predictors of infant HIV testing in multivariate analyses. In conclusion, women who reported an active role in decision-making trended toward a higher likelihood of uptake of infant testing in the PMTCT cascade. Larger studies are needed to evaluate the impact of empowerment initiatives on the PMTCT service utilization overall and infant testing in particular.

Hybrid stochastic framework predicts efficacy of prophylaxis against HIV: An example with different dolutegravir prophylaxis schemes.

PubMed

Duwal, Sulav; Dickinson, Laura; Khoo, Saye; von Kleist, Max

2018-06-01

To achieve the 90-90-90 goals set by UNAIDS, the number of new HIV infections needs to decrease to approximately 500,000 by 2020. One of the 'five pillars' to achieve this goal is pre-exposure prophylaxis (PrEP). Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP. Despite its advantages, Truvada is costly and requires individuals to adhere to the once-daily regimen. To improve PrEP, many next-generation regimen, including long-acting formulations, are currently investigated. However, pre-clinical testing may not guide candidate selection, since it often fails to translate into clinical efficacy. On the other hand, quantifying prophylactic efficacy in the clinic is ethically problematic and requires to conduct long (years) and large (N>1000 individuals) trials, precluding systematic evaluation of candidates and deployment strategies. To prioritize- and help design PrEP regimen, tools are urgently needed that integrate pharmacological-, viral- and host factors determining prophylactic efficacy. Integrating the aforementioned factors, we developed an efficient and exact stochastic simulation approach to predict prophylactic efficacy, as an example for dolutegravir (DTG). Combining the population pharmacokinetics of DTG with the stochastic framework, we predicted that plasma concentrations of 145.18 and 722.23nM prevent 50- and 90% sexual transmissions respectively. We then predicted the reduction in HIV infection when DTG was used in PrEP, PrEP 'on demand' and post-exposure prophylaxis (PEP) before/after virus exposure. Once daily PrEP with 50mg oral DTG prevented 99-100% infections, and 85% of infections when 50% of dosing events were missed. PrEP 'on demand' prevented 79-84% infections and PEP >80% when initiated within 6 hours after virus exposure and continued for as long as possible. While the simulation framework can easily be adapted to other PrEP candidates, our simulations indicated that oral 50mg DTG is non-inferior to Truvada. Moreover, the predicted 90% preventive concentrations can guide release kinetics of currently developed DTG nano-formulations.

Intention to comply with post-exposure management among nurses exposed to blood and body fluids in Taiwan: application of the theory of planned behaviour.

PubMed

Ko, N-Y; Yeh, S-H; Tsay, S-L; Ma, H-J; Chen, C-H; Pan, S-M; Feng, M-C; Chiang, M-C; Lee, Y-W; Chang, L-H; Jang, J-F

2011-04-01

Nurses are at significant risk from occupationally acquired bloodborne virus infections following a needlestick and sharps injury. This study aimed to apply the theory of planned behaviour (TPB) to predict nurses' intention to comply with occupational post-exposure management. A cross-sectional survey was applied to select registered nurses who worked in human immunodeficiency virus (HIV)-designated hospitals. An anonymous, self-administered questionnaire based on the TPB was distributed to 1630 nurses and 1134 (69.5%) questionnaires were returned. From these, a total of 802 nurses (71%) reported blood and body fluid exposure incidents during 2003-2005 and this group was used for analysis. Only 44.6% of the 121 exposed nurses who were prescribed post-exposure prophylaxis (PEP) by infectious disease doctors returned to the clinic for interim monitoring, and only 56.6% of exposed nurses confirmed their final serology status. Structural equation modelling was used to test the TPB indicating perceived behavioural control (the perception of the difficulty or ease of PEP management, β=0.58), subjective norm (the perception of social pressure to adhere to PEP, β=0.15), and attitudes (β=0.12) were significant direct effects on nurses' intention to comply with post-exposure management. The hypothesised model test indicated that the model fitted with the expected relationships and directions of theoretical constructs [χ(2) (14, N=802)=23.14, P=0.057, GFI=0.987, RMSEA=0.039]. The TPB model constructs accounted for 54% of the variance in nurses' intention to comply with post-exposure management. The TPB is an appropriate model for predicting nurses' intention to comply with post-exposure management. Healthcare facilities should have policies to decrease the inconvenience of follow-up to encourage nurses to comply with post-exposure management. Copyright © 2010 the Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis.

PubMed

Edstein, M D; Nasveld, P E; Kocisko, D A; Kitchener, S J; Gatton, M L; Rieckmann, K H

2007-03-01

In an open-label sequential cohort study, we compared gastrointestinal (GI) disturbances and plasma tafenoquine concentrations after administration of single-dose (400mg daily x 3 days; n=76 males, 11 females) and split-dose (200 mg twice daily x 3 days; n=73 males, 13 females) tafenoquine regimens in healthy Australian Defence Force volunteers for post-exposure malaria prophylaxis. The female and male volunteers had comparable demographic characteristics (age, weight, height) in the single- and split-dose treatment groups. GI disturbances were generally mild and self-limiting for both groups. The frequency of nausea and abdominal distress was over two-fold higher in females than in males for both treatment groups. Reporting of GI disturbances in the single-dose group differed significantly between males and females, but this gender difference was not seen for the split-dose group. In those volunteers who experienced GI disturbances, the mean plasma tafenoquine concentrations 12 h after the last dose of tafenoquine were approximately 1.3-fold higher in females than in males (means+/-SD: 737+/-118 ng/ml vs. 581+/-113 ng/ml). These preliminary findings suggest that further studies are required in a larger number of females to determine whether there is a need to reduce the dose of tafenoquine to minimise GI disturbances in females.

High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya.

PubMed

Van der Elst, Elisabeth Maria; Mbogua, Judie; Operario, Don; Mutua, Gaudensia; Kuo, Caroline; Mugo, Peter; Kanungi, Jennifer; Singh, Sagri; Haberer, Jessica; Priddy, Frances; Sanders, Eduard Joachim

2013-07-01

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

Leptospirosis in three workers on a dairy farm with unvaccinated cattle.

PubMed

Benschop, Jackie; Collins-Emerson, Julie; Maskill, Allie; O'Connor, Patrick; Tunbridge, Margaret; Yupiana, Yuni; Weston, Jenny

2017-09-22

We report a one-health investigation of three cases of leptospirosis on a dairy farm with unvaccinated cattle in New Zealand. The cases are discussed in the context of diagnostics, risk factors, persistence of symptoms and outbreak mitigation measures. Clinical and laboratory records from the human cases were reviewed and serological and molecular investigations were conducted into the Leptospira status of cattle and pigs on the farm. Cases presented early in their illness and all three were confirmed within seven days of onset of symptoms by urine PCR and within 18 days by convalescent MAT (two Hardjo, one Pomona). Cattle and pigs had serological evidence of recent infection with Hardjo/Pomona and Pomona/Copenhageni respectively. Pigs were slaughtered and cattle were vaccinated. Post-exposure prophylaxis was given to staff in-contact with the milking herd until the herd had antibiotic treatment at drying-off (approximately four months after the initial case). The utility of PCR testing for Leptospira DNA as both an early and rapid test for leptospirosis was demonstrated. Two of three cases reported persistence of symptoms at least six months after the acute episode and one of these remains unable to work. Risk mitigation measures such as post-exposure prophylaxis, animal vaccination, heightened clinical suspicion of leptospirosis and recognition of context specific risk factors (eg, effluent spreading) demonstrate the value of medical and veterinary experts working together.

Unconsented HIV Testing in Cases of Occupational Exposure: Ethics, Law, and Policy

PubMed Central

Cowan, Ethan; Macklin, Ruth

2012-01-01

Post-exposure prophylaxis (PEP) has substantially reduced the risk of acquiring human immunodeficiency virus (HIV) after an occupational exposure; nevertheless, exposure to HIV remains a concern for emergency department providers. According to published guidelines, PEP should be taken only when source patients are HIV positive or have risk factors for HIV. Initiating PEP when source patients are uninfected puts exposed persons at risk from taking toxic drugs with no compensating benefit. Forgoing PEP if the source is infected results in increased risk of acquiring HIV. What should be done if source patients refuse HIV testing? Is it justifiable to test the blood of these patients over their autonomous objection? The authors review current law and policy and perform an ethical analysis to determine if laws permitting unconsented testing in cases of occupational exposure can be ethically justified. PMID:22994417

A systematic review and meta-analysis of vertical transmission route of HIV in Ethiopia.

PubMed

Endalamaw, Aklilu; Demsie, Amare; Eshetie, Setegn; Habtewold, Tesfa Dejenie

2018-06-22

The burden of mother-to-child transmission rate of HIV is high and risk factors are common in Ethiopia. This systematic review and meta-analysis intended to provide the pooled estimation of mother-to-child transmission rate and its risk factors in Ethiopia. We searched PubMed, Google Scholar, EMBASE and Web of Science electronic databases for all available references. We included observational studies including case-control, cohort, and cross-sectional studies. The search was further limited to studies conducted in Ethiopia and publish in English. Heterogeneity was checked using the I 2 statistic. Egger's test and the funnel plot were used to assess publication bias. A meta-analysis using a weighted inverse variance random-effects model was performed. A total of 18 studies with 6253 individuals were included in this systematic review and meta-analysis. Of these, 14 studies with 4624 individuals were used to estimate the prevalence. The estimated pooled prevalence of mother-to-child transmission of HIV was 11.4% (95% CI = 9.1-13.7). The pooled adjusted odds ratio (AOR) of mother-to-child transmission of HIV for the infants from rural area was 3.8 (95% CI = 1.4 to 6.3), infants delivered at home was 3.2 (95% CI = 1.2 to 5.2), infant didn't take antiretroviral prophylaxis was 5.8 (95% CI = 1.5 to 10.3), mother didn't take antiretroviral prophylaxis was 6.1 (95% CI = 2.5 to 9.6), mothers didn't receive PMTCT intervention was 5.1 (95% CI = 1.6, 8.6), and on mixed feeding was 4.3 (95% CI = 1.8 to 6.7). This systematic review and meta-analysis showed that mother-to-child transmission rate of HIV was high in Ethiopia. Being from the rural residence, home delivery, not taking antiretroviral prophylaxis, the absence of PMTCT intervention, and mixed infant feeding practices increased the risk of HIV transmission. It is registered in the Prospero database: (PROSPERO 2017: CRD42017078232 ).

Human rabies in India: an audit from a rabies diagnostic laboratory.

PubMed

Mani, Reeta Subramaniam; Anand, Ashwini Manoor; Madhusudana, Shampur Narayan

2016-04-01

Rabies, an acute progressive encephalomyelitis, continues to be a serious public health problem in India and many other countries in Asia and Africa. The low level of commitment to rabies control is partly attributable to challenges in laboratory diagnosis and lack of adequate surveillance to indicate the disease burden. A laboratory audit of human rabies cases was undertaken to disseminate information on the clinical, demographic, prophylactic and most importantly the laboratory diagnostic aspects of rabies. A retrospective analysis of all clinically suspected human rabies cases, whose samples were received at a rabies diagnostic laboratory in South India in the last 3 years, was performed. Clinical and demographic details of patients were obtained. The clinical samples included cerebrospinal fluid (CSF), serum, saliva and nuchal skin biopsy collected antemortem, and brain tissue obtained post-mortem. Various laboratory tests were performed for diagnosis. Clinical samples from 128 patients with suspected rabies, from 11 states in India, were received for diagnostic confirmation. About 94% of the victims reported dog-bites, more than a third of them were children and most of the victims did not receive adequate post-exposure prophylaxis. Antemortem confirmation of rabies by a combination of laboratory diagnostic assays (detection of viral RNA in CSF, skin and saliva, and neutralising antibodies in CSF) could be achieved in 40.6% cases. Increasing awareness about adequate post-exposure prophylaxis, additional rabies diagnostic facilities, and enhanced human and animal rabies surveillance to indicate the true disease burden are essential to control this fatal disease. © 2016 John Wiley & Sons Ltd.

Integrated Bio-behavioral Approach to Improve Adherence to Pre-exposure Prophylaxis and Reduce HIV Risk in People Who Use Drugs: A Pilot Feasibility Study.

PubMed

Shrestha, Roman; Altice, Frederick L; Karki, Pramila; Copenhaver, Michael M

2018-03-26

This study reports the feasibility, acceptability, and preliminary efficacy of the bio-behavioral community-friendly health recovery program-an integrated, HIV prevention intervention to improve pre-exposure prophylaxis (PrEP) adherence and HIV-risk reduction behaviors among high-risk people who use drugs. We used a within-subjects, pretest-posttest follow-up design to recruit participants, who were HIV-uninfected, methadone-maintained and reported HIV-risk behaviors and had initiated PrEP (n = 40; males: 55%). Participants were assessed at baseline (T 0 ), immediately post-intervention (4 weeks: T 4 ) and 4 weeks post-intervention (T 8 ). Immediately after completing the four weekly intervention groups, participants underwent a post-intervention assessment including in-depth qualitative interviews. Feasibility was high, assessed by participant willingness to enroll (90.1%) and retention (95%). Results showed that participants were highly satisfied and perceived the intervention as valuable and acceptable [mean: 81.3 (range 0-100)]. Significant enhancements in self-reported PrEP adherence [F(2,74) = 7.500, p = 0.001] and PrEP-related knowledge [F(2,74) = 3.828, p = 0.026] were observed. Drug-related (e.g., injection of drugs, sharing of injection equipment) and sex-related (e.g., number of sexual partners, condomless sex) risk behaviors were reduced, while information, motivation, and behavioral skills (IMB) constructs increased. The results support feasibility and high acceptability and support further examination of the efficacy of this combination bio-behavioral intervention in a prospective clinical trial.

Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda

PubMed Central

Bartelink, Imke H.; Savic, Rada M.; Mwesigwa, Julia; Achan, Jane; Clark, Tamara; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Young, Sera L.; Gandhi, Monica; Havlir, Diane; Cohan, Deborah; Aweeka, Francesca

2013-01-01

Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. 80% of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m2. Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV −33%, EFV −15%, ritonavir −17%) compared to well-nourished controls [p < 0.001], attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% [p < 0.001], whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure [p < 0.001], explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority. PMID:24038035

Rabies: changing prophylaxis and new insights in pathophysiology.

PubMed

Ugolini, Gabriella; Hemachudha, Thiravat

2018-02-01

Despite great progress in decoding disease mechanisms, rabies remains one of the leading causes of human death worldwide. Towards the elimination of human rabies deaths by 2030, feasible and affordable post (PEP) and pre-exposure prophylaxis (PrEP) must be available with expansion to rural areas in rabies endemic countries. Vaccination and population control of dogs, principal reservoirs and transmitters, must be done in concert. Advances in the understanding of rabies neuropathogenesis and pathophysiology are reviewed, including recent experimental findings on host- and virus-specific mechanisms mediating neuronal survival and explaining clinical differences in furious and paralytic rabies. The forthcoming World Health Organization guide on rabies based on pathogenesis and immunization mechanisms data with support by clinical evidence provide new accelerated 1 week intradermal PrEP and PEP schedules. Rabies immunoglobulin injected into the wound only is endorsed at amounts not exceeding the dose interfering with active immunization. Potential therapeutics as designed in accord with rabies neuro-pathophysiology are plausible. Clinical practice and rabies awareness can be leveraged by transboundary collaboration among different areas. Advancement in prophylaxis and perspectives on animal control offer a new path to conquer rabies by 2030.

Protecting children from rabies with education and pre-exposure prophylaxis: A school-based campaign in El Nido, Palawan, Philippines

PubMed Central

Deray, Raffy; Rivera, Cesar; Gripon, Shiela; Ulanday, Corazon; Roces, Maria Concepcion; Attlan, Michael; Demont, Clarisse; Kieffer, Alexia; Miranda, Mary Elizabeth

2018-01-01

Background Rabies remains endemic in the Philippines. A study was conducted in El Nido, Palawan, Philippines to: (i) detect the true incidence of animal bites in school children aged 5–14 years using active surveillance and compare these data to estimates from the existing passive surveillance system, (ii) evaluate the impact of rabies prevention education and pre-exposure prophylaxis (PrEP) on animal bite incidence, and (iii) assess the health economic impact of the interventions. Methodology and principal findings A cohort of 4,700 school children was followed-up for any suspect rabies exposures between January 2011 and December 2012. Data on animal bite incidence from the study cohort were compared to that obtained from a review of consultation records at the Animal Bite Treatment Center (ABTC). PrEP was offered to children in all 27 public elementary schools in El Nido (in January to February 2012). Teachers were given a manual for integrating rabies in the public elementary school curriculum during the school year 2012–13. Active surveillance of the cohort revealed a higher incidence of suspect rabies exposures than that from passive surveillance. Despite a decrease in the number of Category III bites, there was no significant decrease in overall bite incidence as a result of the interventions. However, there was an increase in rabies awareness among school children in all grade levels. There was also a high level of acceptability of PrEP. Children who received PrEP and subsequently were bitten only needed two booster doses for post-exposure prophylaxis, resulting in substantial cost-savings. Conclusions/significance The true burden of animal bites remains underestimated in ABTC records. PrEP is advantageous in selected population groups, i.e. school-aged children in rabies endemic areas with limited access to animal and human rabies prevention services. Educating school children is beneficial. Strengthening veterinary interventions to target the disease at source is important. PMID:29293571

Protecting children from rabies with education and pre-exposure prophylaxis: A school-based campaign in El Nido, Palawan, Philippines.

PubMed

Deray, Raffy; Rivera, Cesar; Gripon, Shiela; Ulanday, Corazon; Roces, Maria Concepcion; Amparo, Anna Charinna; Attlan, Michael; Demont, Clarisse; Kieffer, Alexia; Miranda, Mary Elizabeth

2018-01-01

Rabies remains endemic in the Philippines. A study was conducted in El Nido, Palawan, Philippines to: (i) detect the true incidence of animal bites in school children aged 5-14 years using active surveillance and compare these data to estimates from the existing passive surveillance system, (ii) evaluate the impact of rabies prevention education and pre-exposure prophylaxis (PrEP) on animal bite incidence, and (iii) assess the health economic impact of the interventions. A cohort of 4,700 school children was followed-up for any suspect rabies exposures between January 2011 and December 2012. Data on animal bite incidence from the study cohort were compared to that obtained from a review of consultation records at the Animal Bite Treatment Center (ABTC). PrEP was offered to children in all 27 public elementary schools in El Nido (in January to February 2012). Teachers were given a manual for integrating rabies in the public elementary school curriculum during the school year 2012-13. Active surveillance of the cohort revealed a higher incidence of suspect rabies exposures than that from passive surveillance. Despite a decrease in the number of Category III bites, there was no significant decrease in overall bite incidence as a result of the interventions. However, there was an increase in rabies awareness among school children in all grade levels. There was also a high level of acceptability of PrEP. Children who received PrEP and subsequently were bitten only needed two booster doses for post-exposure prophylaxis, resulting in substantial cost-savings. The true burden of animal bites remains underestimated in ABTC records. PrEP is advantageous in selected population groups, i.e. school-aged children in rabies endemic areas with limited access to animal and human rabies prevention services. Educating school children is beneficial. Strengthening veterinary interventions to target the disease at source is important.

Natural Conception May Be an Acceptable Option in HIV-Serodiscordant Couples in Resource Limited Settings.

PubMed

Sun, Lijun; Wang, Fang; Liu, An; Xin, Ruolei; Zhu, Yunxia; Li, Jianwei; Shao, Ying; Ye, Jiangzhu; Chen, Danqing; Li, Zaicun

2015-01-01

Many HIV serodiscordant couples have a strong desire to have their own biological children. Natural conception may be the only choice in some resource limited settings but data about natural conception is limited. Here, we reported our findings of natural conception in HIV serodiscordant couples. Between January 2008 and June 2014, we retrospectively collected data on 91 HIV serodiscordant couples presenting to Beijing Youan Hospital with childbearing desires. HIV counseling, effective ART on HIV infected partners, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in negative female partners and timed intercourse were used to maximally reduce the risk of HIV transmission. Of the 91 HIV serodiscordant couples, 43 were positive in male partners and 48 were positive in female partners. There were 196 unprotected vaginal intercourses, 100 natural conception and 97 newborns. There were no cases of HIV seroconversion in uninfected sexual partners. Natural conception may be an acceptable option in HIV-serodiscordant couples in resource limited settings if HIV-positive individuals have undetectable viremia on HAART, combined with HIV counseling, PrEP, PEP and timed intercourse.

Comparing Provider and Client Preferences for HIV Prevention Services in South Africa among Men Who Have Sex with Men.

PubMed

Shaver, John; Sullivan, Patrick; Siegler, Aaron; de Voux, Alex; Phaswana-Mafuya, Nancy; Bekker, Linda-Gail; Baral, Stefan D; Wirtz, Andrea L; Beyrer, Chris; Brown, Ben; Stephenson, Rob

Combination prevention efforts are now recommended toward reducing HIV incidence among men who have sex with men (MSM). Understanding the perceptions of both MSM and service providers is critical to informing the development of prevention packages and ultimately improving intervention effectiveness. This study assessed the preferences of MSM and health service providers in the administration of HIV-prevention efforts. Qualitative data were gathered from a series of separate MSM and health care provider focus groups in 2 South African cities. Participants discussed HIV-prevention services and MSM client experiences within South Africa and identified the 3 most important clinic characteristics and 3 most important HIV-prevention services for MSM clients. Priorities indicated by both MSM and health care providers were confidentiality of visit, friendly staff, and condoms, while discrepancies existed between MSM and providers regarding provider consistency and the provision of pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) and lubricant as prevention methods. Effective interventions must address these discrepancies through the design of intervention and provider training to optimally accommodate MSM.

"It Was Not My Aim to Sleep There": The Impact of Timing and Location of Sex on Adherence to Coitally-Dependent HIV Pre-exposure Prophylaxis.

PubMed

Scorgie, Fiona; Stadler, Jonathan; Baron, Deborah; Ju, Susan; Ikaneng, Tshepiso; Mabude, Zonke; Makgopa, Sylvia; Malefo, Matshidiso A; Manenzhe, Kgahlisho N; Mazibuko, Thulani; Ntjana, Hilda; Nkala, Busi; Palanee-Phillips, Thesla; Gray, Glenda; Rees, Helen; Delany-Moretlwe, Sinead

2018-06-16

The FACTS 001 trial found that vaginal pre- and post-coital application of 1% tenofovir gel did not prevent HIV-1 infection amongst young South African women. The trial included a multi-faceted approach to adherence support and collected objective and self-reported adherence measures. Using qualitative data collected from a random sub-set of FACTS 001 participants (135 in-depth interviews at product discontinuation and 13 focus group discussions at dissemination of trial results), we explore the importance of 'place' and 'timing' in shaping acts of sexual intimacy and product adherence. Demographically, this qualitative sub-sample is similar to the trial cohort of predominantly young, unemployed women living with parents or other family members. Sexual intimacy was largely unpredictable and happened across multiple locations in which women had limited privacy, autonomy, or control over the timing of sex. This made adherence to the dosing strategy challenging. Findings may inform the development of future event-driven pre-exposure prophylaxis regimens or products.

Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009-2014.

PubMed

Si, Damin; Marquess, John; Donnan, Ellen; Harrower, Bruce; McCall, Bradley; Bennett, Sonya; Lambert, Stephen

2016-12-01

Australian bat lyssavirus (ABLV) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses. To date, the only three known human ABLV cases, all fatal, have been reported from Queensland, Australia. ABLV is widely distributed in Australian bats, and any bite or scratch from an Australian bat is considered a potential exposure to ABLV. Potential exposure to ABLV has been a notifiable condition in Queensland since 2005. We analysed notification data for potential exposures occurring between 2009 and 2014. There were 1,515 potential exposures to ABLV notified in Queensland, with an average annual notification rate of 5.6 per 100,000 population per year. The majority of notified individuals (96%) were potentially exposed to ABLV via bats, with a small number of cases potentially exposed via two ABLV infected horses and an ABLV infected human. The most common routes of potential exposure were through bat scratches (47%) or bites (37%), with less common routes being mucous membrane/broken skin exposure to bat saliva/brain tissue (2.2%). Intentional handling of bats by the general public was the major cause of potential exposures (56% of notifications). Examples of these potential exposures included people attempting to rescue bats caught in barbed wire fences/fruit tree netting, or attempting to remove bats from a home. Following potential exposures, 1,399 cases (92%) were recorded as having appropriate post-exposure prophylaxis (PEP) as defined in national guidelines, with the remainder having documentation of refusal or incomplete PEP. Up to a quarter of notifications occurred after two days from the potential exposure, but with some delays being more than three weeks. Of 393 bats available for testing during the reporting period, 20 (5.1%) had ABLV detected, including four species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat). Public health strategies should address the strong motivation of some members of the public to help injured bats or bats in distress, by emphasising that their action may harm the bat and put themselves at risk of the fatal ABLV infection. Alternative messaging should include seeking advice from professional animal rescue groups, or in the event of human contact, public health units. Further efforts are required to ensure that when potential exposure occurs, timely reporting and appropriate post-exposure prophylaxis occur.

Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009−2014

PubMed Central

Si, Damin; Marquess, John; Donnan, Ellen; Harrower, Bruce; McCall, Bradley; Bennett, Sonya; Lambert, Stephen

2016-01-01

Background Australian bat lyssavirus (ABLV) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses. To date, the only three known human ABLV cases, all fatal, have been reported from Queensland, Australia. ABLV is widely distributed in Australian bats, and any bite or scratch from an Australian bat is considered a potential exposure to ABLV. Methodology/Principal Findings Potential exposure to ABLV has been a notifiable condition in Queensland since 2005. We analysed notification data for potential exposures occurring between 2009 and 2014. There were 1,515 potential exposures to ABLV notified in Queensland, with an average annual notification rate of 5.6 per 100,000 population per year. The majority of notified individuals (96%) were potentially exposed to ABLV via bats, with a small number of cases potentially exposed via two ABLV infected horses and an ABLV infected human. The most common routes of potential exposure were through bat scratches (47%) or bites (37%), with less common routes being mucous membrane/broken skin exposure to bat saliva/brain tissue (2.2%). Intentional handling of bats by the general public was the major cause of potential exposures (56% of notifications). Examples of these potential exposures included people attempting to rescue bats caught in barbed wire fences/fruit tree netting, or attempting to remove bats from a home. Following potential exposures, 1,399 cases (92%) were recorded as having appropriate post-exposure prophylaxis (PEP) as defined in national guidelines, with the remainder having documentation of refusal or incomplete PEP. Up to a quarter of notifications occurred after two days from the potential exposure, but with some delays being more than three weeks. Of 393 bats available for testing during the reporting period, 20 (5.1%) had ABLV detected, including four species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat). Conclusions/Significance Public health strategies should address the strong motivation of some members of the public to help injured bats or bats in distress, by emphasising that their action may harm the bat and put themselves at risk of the fatal ABLV infection. Alternative messaging should include seeking advice from professional animal rescue groups, or in the event of human contact, public health units. Further efforts are required to ensure that when potential exposure occurs, timely reporting and appropriate post-exposure prophylaxis occur. PMID:28033365

Use of HIV pre-exposure prophylaxis during the preconception, antepartum and postpartum periods at two United States medical centers.

PubMed

Seidman, Dominika L; Weber, Shannon; Timoney, Maria Teresa; Oza, Karishma K; Mullins, Elizabeth; Cohan, Deborah L; Wright, Rodney L

2016-11-01

Pregnancy may increase a woman's susceptibility to HIV. Maternal HIV acquisition during pregnancy and lactation is associated with increased perinatal and lactational HIV transmission. There are no published reports of preexposure prophylaxis use after the first trimester of pregnancy or during lactation. The purpose of this study was to report the use of preexposure prophylaxis and to identify gaps in HIV prevention services for women who were at substantial risk of HIV preconception and during pregnancy and lactation at 2 United States medical centers. Chart review was performed on women who were identified as "at significant risk" for HIV acquisition preconception (women desiring pregnancy) and during pregnancy and lactation at 2 medical centers in San Francisco and New York from 2010-2015. Women were referred to specialty clinics for women who were living with or were at substantial risk of HIV. Twenty-seven women who were identified had a median age of 27 years. One-half of the women had unstable housing, 22% of the women had ongoing intimate partner violence, and 22% of the women had active substance use. Twenty-six women had a male partner living with HIV, and 1 woman had a male partner who had sex with men. Of the partners who were living with HIV, 73% (19/26) were receiving antiretroviral therapy, and 42% (11/26) had documented viral suppression. Thirty-nine percent (10/26) of partners had known detectable virus, and 19% (5/26) had unknown viral loads. Women were identified by clinicians, health educators, and health departments. Approximately one-third of the women were identified preconception (8/27); the majority of the women were identified during pregnancy (18/27) with a median gestational age of 20 weeks (interquartile range, 11-23), and 1 woman was identified in the postpartum period. None of the pregnant referrals had received safer conception counseling to reduce HIV transmission. Twenty-six percent of all women (7/27) were eligible for postexposure prophylaxis at referral, of whom 57% (4/7) were offered postexposure prophylaxis. In 30% (8/27), the last HIV exposure was not assessed and postexposure prophylaxis was not offered. The median time from identification as "at substantial risk" to consultation was 30 days (interquartile range, 2-62). Two women were lost to follow up before consultation. One woman who was identified as "at significant risk" was not referred because of multiple pregnancy complications. She remained in obstetrics care and was HIV-negative at delivery but was lost to follow up until 10 months after delivery when she was diagnosed with HIV. No other seroconversions were identified. Of referrals who presented and were offered preexposure prophylaxis, 67% women (16/24) chose to take it, which was relatively consistent whether the women were preconception (5/8), pregnant (10/15), or after delivery (1/1). Median length of time on preexposure prophylaxis was 30 weeks (interquartile range, 20-53). One-half of women (10/20) who were in care at delivery did not attend a postpartum visit. Women at 2 United States centers frequently chose to use preexposure prophylaxis for HIV prevention when it was offered preconception and during pregnancy and lactation. Further research and education are needed to close critical gaps in screening for women who are at risk of HIV for pre- and postexposure prophylaxis eligibility and gaps in care linkage before and during pregnancy and lactation. Postpartum women are particularly vulnerable to loss-to-follow-up and miss opportunities for safe and effective HIV prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

First population-level effectiveness evaluation of a national programme to prevent HIV transmission from mother to child, South Africa.

PubMed

Goga, Ameena E; Dinh, Thu-Ha; Jackson, Debra J; Lombard, Carl; Delaney, Kevin P; Puren, Adrian; Sherman, Gayle; Woldesenbet, Selamawit; Ramokolo, Vundli; Crowley, Siobhan; Doherty, Tanya; Chopra, Mickey; Shaffer, Nathan; Pillay, Yogan

2015-03-01

There is a paucity of data on the national population-level effectiveness of preventing mother-to-child transmission (PMTCT) programmes in high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010. A facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4-8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions. Nationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively). SA, a high-HIV-prevalence middle income country achieved <5% MTCT by 4-8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs urgent assessment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP).

PubMed

Liu, Albert Y; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P; Greenblatt, Ruth M; Gandhi, Monica

2014-01-01

Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs. ClinicalTrials.gov NCT00903084.

Strong Relationship between Oral Dose and Tenofovir Hair Levels in a Randomized Trial: Hair as a Potential Adherence Measure for Pre-Exposure Prophylaxis (PrEP)

PubMed Central

Liu, Albert Y.; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L.; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P.; Greenblatt, Ruth M.; Gandhi, Monica

2014-01-01

Background Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. Methods A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Results Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60–93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. Conclusions This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs. Trial Registration ClinicalTrials.gov +NCT00903084. PMID:24421901

The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.

PubMed

Hannaford, Alisse; Lipshie-Williams, Madeleine; Starrels, Joanna L; Arnsten, Julia H; Rizzuto, Jessica; Cohen, Phillip; Jacobs, Damon; Patel, Viraj V

2018-04-01

Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional research approaches may not comprehensively capture current factors important for designing and implementing PrEP related interventions.

[Prophylaxis and therapy of post-traumatic stress disorder with propranolol: evidence and ethical analysis].

PubMed

Kühlmeyer, K; Jox, R J

2013-10-01

The beta-antagonistic agent propranolol is increasingly being used in clinical trials for the prophylaxis and treatment of post-traumatic stress disorder (PTSD). This article discusses the evidence for the effectiveness of propranolol in the prophylaxis and treatment of PTSD and the ethical implications of research on these treatment approaches. The efficacy of a prophylactic or therapeutic use could not be shown during the last decade. Both treatment approaches raise ethical questions that should already be addressed during the clinical trials.

Antiretroviral treatment for HIV infection: Swedish recommendations 2016.

PubMed

Eriksen, Jaran; Albert, Jan; Blaxhult, Anders; Carlander, Christina; Flamholc, Leo; Gisslén, Magnus; Josephson, Filip; Karlström, Olof; Navér, Lars; Svedhem, Veronica; Yilmaz, Aylin; Sönnerborg, Anders

2017-01-01

The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases. First-line treatment for previously untreated individuals includes dolutegravir, boosted darunavir or efavirenz with either abacavir/lamivudine or tenofovir (TDF/TAF)/emtricitabine. Pre-exposure prophylaxis (PrEP) is recommended for high-risk individuals. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine ( http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ ) ( Table 1 ). This document does not cover treatment of opportunistic infections and tumours. [Table: see text].

Correlates of Use of Timed Unprotected Intercourse to Reduce Horizontal Transmission Among Ugandan HIV Clients with Fertility Intentions

PubMed Central

Wagner, Glenn J.; Goggin, Kathy; Mindry, Deborah; Beyeza-Kashesya, Jolly; Finocchario-Kessler, Sarah; Woldetsadik, Mahlet Atakilt; Khanakwa, Sarah; Wanyenze, Rhoda K.

2014-01-01

We examined the correlates of use of safer conception methods (SCM) in a sample of 400 Ugandan HIV clients (75% female; 61% on antiretroviral therapy; 61% with HIV-negative or unknown status partners) in heterosexual relationships with fertility intentions. SCM assessed included timed unprotected intercourse, manual self-insemination, sperm washing, and pre-exposure prophylaxis (PrEP). In the 6 months prior to baseline, 47 (12%) reported using timed unprotected intercourse to reduce risk of HIV infection (or re-infection), none had used manual self-insemination or sperm washing, and 2 had used PrEP. In multiple regression analysis, correlates of use of timed unprotected intercourse included greater perceptions of partner’s willingness to use SCM and providers’ stigma of childbearing among people living with HIV, higher SCM knowledge, and desire for a child within the next 6 months. These findings highlight the need for policy and provider training regarding integration of couples’ safer conception counselling into HIV care. PMID:25280448

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

PubMed

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

2015-01-01

Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

PubMed

Gibb, Diana M; Kizito, Hilda; Russell, Elizabeth C; Chidziva, Ennie; Zalwango, Eva; Nalumenya, Ruth; Spyer, Moira; Tumukunde, Dinah; Nathoo, Kusum; Munderi, Paula; Kyomugisha, Hope; Hakim, James; Grosskurth, Heiner; Gilks, Charles F; Walker, A Sarah; Musoke, Phillipa

2012-01-01

Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens. Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children. www.controlled-trials.com ISRCTN13968779

6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial.

PubMed

Samandari, Taraz; Agizew, Tefera B; Nyirenda, Samba; Tedla, Zegabriel; Sibanda, Thabisa; Shang, Nong; Mosimaneotsile, Barudi; Motsamai, Oaitse I; Bozeman, Lorna; Davis, Margarett K; Talbot, Elizabeth A; Moeti, Themba L; Moffat, Howard J; Kilmarx, Peter H; Castro, Kenneth G; Wells, Charles D

2011-05-07

In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33-0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09-0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38-1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0·50, 95% CI 0·26-0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups. In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. US Centers for Disease Control and Prevention and US Agency for International Development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post partum: results of the BAN Study

PubMed Central

Corbett, Amanda H; Kayira, Dumbani; White, Nicole R; Davis, Nicole L; Kourtis, Athena P; Chasela, Charles; Martinson, Francis; Phiri, Grace; Musisi, Bonaface; Kamwendo, Deborah; Hudgens, Michael G; Hosseinipour, Mina C; Nelson, Julie AE; Ellington, Sascha R; Jamieson, Denise J; van der Horst, Charles; Kashuba, Angela

2014-01-01

Background An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral, and Nutrition study was performed to describe drug exposure and antiviral response. Methods Women using Combivir®[zidovudine (ZDV)+ lamivudine (3TC)]+Aluvia®[lopinavir/ritonavir(LPV/RTV)] were enrolled. Breast milk (BM) and mother and infant plasma (MP, IP) samples were obtained over 6hrs after observed dosing at 6, 12, or 24wks post-partum for drug concentrations and HIV RNA. Results 30 mother/infant pairs (10 each at 6, 12,and 24wks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, while LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24wks. The majority (98.3%) of BM concentrations were >HIVwt IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. Conclusions ZDV and 3TC concentrated in BM while LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low ARV concentrations in IP suggests prevention of transmission while breast feeding may be due to ARV effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early. PMID:24464632

4'-Ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591: a novel HIV-1 reverse transcriptase translocation inhibitor.

PubMed

Markowitz, Martin; Sarafianos, Stefan G

2018-07-01

4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a nucleoside reverse transcriptase inhibitor (NRTI) with a novel mechanism of action, unique structure, and amongst NRTIs, unparalleled anti-HIV-1 activity. We will summarize its structure and function, antiviral activity, resistance profile, and potential as an antiretroviral for use in the treatment and preexposure prophylaxis of HIV-1 infection. EFdA is active against wild-type (EC50 as low as 50 pmol/l) and most highly NRTI-resistant viruses. The active metabolite, EFdA-triphosphate, has been shown to have a prolonged intracellular half-life in human and rhesus (Rh) blood cells. As a result, single drug doses tested in simian immunodeficiency virus mac251-infected Rh macaques and HIV-1-infected individuals exhibited robust antiviral activity of 7-10 days duration. Preclinical studies of EFdA as preexposure prophylaxis in the Rh macaque/simian/human immunodeficiency virus low-dose intrarectal challenge model have shown complete protection when given in clinically relevant doses. EFdA is a novel antiretroviral with activity against both wild-type and NRTI-resistant viruses. As a result of the prolonged intracellular half-life of its active moiety, it is amenable to flexibility in dosing of at least daily to weekly and perhaps longer.

Fighting rabies in Eastern Europe, the Middle East and Central Asia--experts call for a regional initiative for rabies elimination.

PubMed

Aikimbayev, A; Briggs, D; Coltan, G; Dodet, B; Farahtaj, F; Imnadze, P; Korejwo, J; Moiseieva, A; Tordo, N; Usluer, G; Vodopija, R; Vranješ, N

2014-05-01

MEEREB is an informal network of rabies experts from the Middle East, Eastern Europe and Central Asia, seeking to eliminate rabies from the region. They met for the second time to review the current rabies situation, both globally and in their respective countries, highlighting current rabies control problems and potential solutions. Success stories in Latin America, in Western Europe, in some Asian countries, as well as in Croatia and Serbia prove that elimination of human rabies is achievable in the MEEREB region. It requires political willingness and cooperation of all stakeholders, including Ministries of Health and of Agriculture; adequate management of animal bites through post-exposure prophylaxis; pre-exposure prophylaxis for populations at high risk of rabies exposure, animal vaccination and humane control of stray dog populations. MEEREB members called for a regional initiative for rabies elimination in Eastern Europe and the Middle East. They are confident that the elimination of human rabies of canine origin can be achieved in the region through adopting a One Health approach, and that campaigns for rabies elimination will have significant benefit for public health, including strengthening the structure for control of other zoonoses. © 2013 Blackwell Verlag GmbH.

AIDS in Brazilian children: history, surveillance, antiretroviral therapy, and epidemiologic transition, 1984-2008.

PubMed

Ramos, Alberto Novaes; Matida, Luiza Harunari; Hearst, Norman; Heukelbach, Jorg

2011-04-01

We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges.

Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus.

PubMed

Martina, Byron E E; Smreczak, Marcin; Orlowska, Anna; Marzec, Anna; Trebas, Pawel; Roose, Jouke M; Zmudzinski, Jan; Gerhauser, Ingo; Wohlsein, Peter; Baumgärtner, Wolfgang; Osterhaus, Albert D M E; Koraka, Penelope

2018-05-26

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-α. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults.

PubMed

Macartney, Kristine; Heywood, Anita; McIntyre, Peter

2014-06-23

The prevention of varicella (chickenpox) using live attenuated varicella vaccines has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States and Australia. Many countries do not routinely immunise children against varicella and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP). To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults. We searched CENTRAL (2014, Issue 1), MEDLINE (1966 to March week 1, 2014), EMBASE (January 1990 to March 2014) and LILACS (1982 to March 2014). We searched for unpublished trials registered on the clinicaltrials.gov and WHO ICTRP websites. RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse events following vaccination. Two review authors independently extracted and analysed data using Review Manager software. We identified three trials involving 110 healthy children who were siblings of household contacts. The included trials varied in study quality, vaccine used, length of follow-up and outcomes measured and, as such, were not suitable for meta-analysis. We identified high or unclear risk of bias in two of the three included studies. Overall, 13 out of 56 vaccine recipients (23%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with fewer than 50 skin lesions). In the three trials, most participants received PEP within three days following exposure; too few participants were vaccinated four to five days post-exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included trial reported on adverse events following immunisation. These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. We identified no RCTs for adolescents or adults. Safety was not adequately addressed.

Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants.

PubMed

Fogel, Jessica M; Mwatha, Anthony; Richardson, Paul; Brown, Elizabeth R; Chipato, Tsungai; Alexandre, Michel; Moodley, Dhayendre; Elbireer, Ali; Mirochnick, Mark; George, Kathleen; Mofenson, Lynne M; Zwerski, Sheryl; Coovadia, Hoosen M; Eshleman, Susan H

2013-04-01

The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis. HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables. NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003). Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.

Risk factors for extended spectrum β-lactamase-producing Escherichia coli versus susceptible E. coli in surgical site infections among cancer patients in Mexico.

PubMed

Montes, Claudia V; Vilar-Compte, Diana; Velazquez, Consuelo; Golzarri, Maria Fernanda; Cornejo-Juarez, Patricia; Larson, Elaine L

2014-10-01

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are of increasing concern as a cause of healthcare-associated infections. Using a matched case-control design, demographics, antibiotic use, and relevant surgical data were obtained for 173 cases (ESBL E. coli surgical site infections, [SSI]) and 173 controls (antibiotic-susceptible E. coli SSI) in an oncology hospital in Mexico City. Conditional logistic regression modeling was used to calculate odds ratios (OR). The mean age of patients was 53.6 years, 214 (62%) were female. Demographics and comorbidities were similar between groups. Although antibiotic prophylaxis was common among both cases and controls (84% and 89%), more than one-half of cases (53%) were given prophylaxis outside the recommended window or were exposed for more than 24 h in comparison to 29% of controls. Patients who received untimely (OR=3.13, 95% confidence interval [CI] 1.5-6.4) and discontinued inappropriately (OR 6.38, 95% CI=2.5-16.2) prophylaxis were more likely to develop an ESBL SSI. In addition, patients with an organ/space infection compared with superficial had a higher rate of a resistant infection (OR 4.2, 95% CI 1.3-13.9). Among patients not given timely or appropriately discontinued prophylaxis, post-operative cephalosporin use (OR 3.3, 95% CI 1.4-7.7) was associated with ESBL E. coli SSIs. The appropriate timing and duration of perioperative antimicrobial prophylaxis were associated with lower risk of ESBL E. coli in SSIs. Even though compliance to antimicrobial prophylaxis guidelines is of the utmost importance, reduced exposure to cephalosporins may also potentially decrease the risk of ESBL SSI.

Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine.

PubMed

Fang, Yuan; Liu, Man-Qing; Chen, Li; Zhu, Zheng-Gang; Zhu, Ze-Rong; Hu, Quan

2016-07-02

Most adverse events (AEs) during the immunization of rabies vaccine were slight, there was little information about the allergic reaction induced by rabies vaccines and had to stop or change the immunization program. Here, we reported a case that a 4-year-old boy had category II exposure to rabies and showed severe allergic reaction after being immunized with lyophilized purified vero cell rabies vaccine (PVRV). After the anti-allergy therapy with hormone, allergy testing indicated medium allergy to egg and milk, and implied the allergic reaction most likely associated with animal-sourced gelatin in lyophilized PVRV. Therefore, a new immunization program with liquid PVRV without stabilizers under the Zegrab regimen (2-1-1) was enrolled at day 7 post-exposure. Although lower than the levels of normal <5 -year population at day 14 and 45, the neutralizing antibody (RVNA) titers of this boy showed adequate protective antibody (≥ 0.5 IU/ml), even after 365 d post-immunization. This study not only highlighted the importance of several types of rabies vaccines co-existing in the market, but also implied the necessary for doctors to fully understand the allergies history of patients prior to immunize rabies vaccine.

Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

PubMed

Kumwenda, Newton I; Hoover, Donald R; Mofenson, Lynne M; Thigpen, Michael C; Kafulafula, George; Li, Qing; Mipando, Linda; Nkanaunena, Kondwani; Mebrahtu, Tsedal; Bulterys, Marc; Fowler, Mary Glenn; Taha, Taha E

2008-07-10

Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.) 2008 Massachusetts Medical Society

Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

PubMed

Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W; Thiebaut, Rodolphe; Cope, Alethea; Scarlatti, Gabriella; Shattock, Robin J

2016-06-01

Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have increased susceptibility to a simian-HIV vaginal challenge), while the microbicide reduced the infection risk compared to that of vaccinated and naive animals. Importantly, the combined interventions provided the greatest level of protection, which was sustained following withdrawal of the microbicide. The data suggest that provision of ARV prophylaxis during vaccination reduces the potential for unexpected increased risks of infection following immunization and augments vaccine efficacy. These findings are important for the potential adoption of ARV prophylaxis as the baseline intervention for future HIV/AIDS vaccines. Copyright © 2016 Le Grand et al.

Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates

PubMed Central

Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W.; Thiebaut, Rodolphe; Scarlatti, Gabriella

2016-01-01

ABSTRACT Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. IMPORTANCE There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have increased susceptibility to a simian-HIV vaginal challenge), while the microbicide reduced the infection risk compared to that of vaccinated and naive animals. Importantly, the combined interventions provided the greatest level of protection, which was sustained following withdrawal of the microbicide. The data suggest that provision of ARV prophylaxis during vaccination reduces the potential for unexpected increased risks of infection following immunization and augments vaccine efficacy. These findings are important for the potential adoption of ARV prophylaxis as the baseline intervention for future HIV/AIDS vaccines. PMID:27009957

Cerebral toxoplasmosis in patients with acquired immune deficiency syndrome in the neurological emergency department of a tertiary hospital.

PubMed

de Oliveira, Gabriela Brito; da Silva, Maria Almerice Lopes; Wanderley, Leandro Batista; da Cunha Correia, Carolina; Ferreira, Eduardo Caetano Brandão; de Medeiros, Zulma Maria; Filho, José Luiz Lima; de Melo, Fábio Lopes; de Araújo, Paulo Sérgio Ramos; Santos, Alfredo Henrique Cecílio Marins

2016-11-01

Cerebral toxoplasmosis is the most common cause of space occupying brain lesion in patients with HIV/AIDS in Brazil. In the post-HAART era, it is responsible for high rates of morbidity and mortality worldwide. This study consists of a case series of 56 patients diagnosed with cerebral toxoplasmosis whose clinical features, brain imaging and cerebrospinal fluid aspects were analyzed. Cerebral toxoplasmosis led to the diagnosis of infection by the human immunodeficiency virus (HIV) in 27 (48.2%) of the patients, while 29 (51.2%) others already knew to be HIV seropositive. However, at the time of diagnosis of cerebral toxoplasmosis, only 9 (16.6%) reported being under antiretroviral therapy and 5 (8.9%) were receiving primary prophylaxis for toxoplasmosis. Headache, strength deficit and fever were the most frequent signs and symptoms throughout the study. Fifty-three patients showed changes consistent with toxoplasmosis in CT or MRI. Thirty-four (60.7%) CSF samples were positive in the indirect haemagglutination test and for the reaction of Toxoplasma gondii IgG ELISA, while 31 (55.4%) were positive in the direct haemagglutination test. Fifty (89.3%) patients underwent first-line treatment for toxoplasmosis. Cerebral toxoplasmosis is still a very relevant neurological disease in individuals with AIDS admitted to neurology emergency departments. Early diagnosis and initiation of empiric treatment and antiretroviral therapy are important for good prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Hospital preparedness in community measles outbreaks—challenges and recommendations for low-resource settings

PubMed Central

Shakoor, Sadia; Mir, Fatima; Zaidi, Anita K. M.; Zafar, Afia

2015-01-01

We have reviewed various strategies involved in containment of measles in healthcare facilities during community outbreaks. The strategies that are more applicable to resource-poor settings, such as natural ventilation, mechanical ventilation with heating and air-conditioning systems allowing unidirectional air-flow, and protection of un-infected patients and healthcare workers (HCWs), have been examined. Ventilation methods need innovative customization for resource-poor settings followed by validation and post-implementation analysis for impact. Mandatory vaccination of all HCWs with two doses of measles-containing vaccine, appropriate post-exposure prophylaxis of immunocompromised inpatients, and stringent admission criteria for measles cases can contribute toward reduction of nosocomial and secondary transmission within facilities. PMID:25882388

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

PubMed Central

Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture. PMID:24303998

Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies

PubMed Central

Vora, N.M.; Orciari, L.A.; Niezgoda, M.; Selvaggi, G.; Stosor, V.; Lyon, G.M.; Wallace, R.M.; Gabel, J.; Stanek, D.R.; Jenkins, P.; Shiferaw, M.; Yager, P.; Jackson, F.; Hanlon, C.A.; Damon, I.; Blanton, J.D.; Recuenco, S.; Franka, R.

2015-01-01

Background The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. Methods As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. Results All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. Conclusions The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies. PMID:25851103

Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies.

PubMed

Vora, N M; Orciari, L A; Niezgoda, M; Selvaggi, G; Stosor, V; Lyon, G M; Wallace, R M; Gabel, J; Stanek, D R; Jenkins, P; Shiferaw, M; Yager, P; Jackson, F; Hanlon, C A; Damon, I; Blanton, J D; Recuenco, S; Franka, R

2015-06-01

The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antibody Maturation and Viral Diversification in HIV-Infected Women

PubMed Central

James, Maria M.; Laeyendecker, Oliver; Sun, Jin; Hoover, Donald R.; Mullis, Caroline E.; Cousins, Matthew M.; Coates, Thomas; Moore, Richard D.; Kelen, Gabor D.; Fowler, Mary Glenn; Kumwenda, Johnstone J.; Mofenson, Lynne M.; Kumwenda, Newton I.; Taha, Taha E.; Eshleman, Susan H.

2013-01-01

Introduction The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women. Methods Samples collected at enrollment (N = 2,561) and 12–24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67). Results In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection. Conclusions Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection. PMID:23460842

Cost-effectiveness analysis of varicella vaccine as post-exposure prophylaxis in Hong Kong.

PubMed

Chui, Ka-Sing; Wu, Hiu-Lok; You, Joyce H S

2014-01-01

The varicella vaccine is an effective post-exposure prophylaxis (PEP) for chickenpox. This study aimed to analyze the cost-effectiveness of PEP using varicella vaccine for pediatric patients from the perspective of the public healthcare provider in Hong Kong. A decision tree was designed to compare cost and clinical outcomes of PEP with varicella vaccine versus no PEP in pediatric patients (aged 1-18 y) susceptible to chickenpox with household exposure. Two tiers of outcome were simulated: (1) total direct medical cost per subject exposed, and (2) the quality-adjusted life-year (QALY) loss associated with chickenpox per subject exposed. Model inputs were retrieved from local epidemiology and the medical literature. A sensitivity analysis was performed on all parameters to test the robustness of model results. The base-case analysis showed PEP with varicella vaccine to be less costly (expected cost USD 320 vs USD 731) with lower QALY loss (0.00423 QALY vs 0.01122 QALY) when compared to no PEP. The sensitivity analysis showed that PEP with varicella vaccine was less costly if PEP effectiveness was > 6.2% or the chickenpox infection rate without PEP was > 8.6%. In 10,000 Monte Carlo simulations, PEP with vaccine was cost-effective over 99% of the time, with a mean cost saving of USD 611 per patient (95% confidence interval USD 602-620; p < 0.001) and lower mean QALY loss of 0.00809 QALY (95% confidence interval 0.00802-0.00816 QALY; p < 0.001). Using varicella vaccine as PEP appears to be a cost-saving strategy to avert QALY loss in susceptible pediatric patients exposed to chickenpox in Hong Kong.

Australian bat lyssavirus: implications for public health.

PubMed

Francis, Joshua R; McCall, Bradley J; Hutchinson, Penny; Powell, Jodie; Vaska, Vikram L; Nourse, Clare

2014-12-11

Australian bat lyssavirus (ABLV) infection in humans is rare but fatal, with no proven effective therapy. ABLV infection can be prevented by administration of a post-exposure prophylaxis regimen of human rabies immunoglobulin and rabies vaccine. All Australian bats (flying foxes and microbats) should be considered to be carrying ABLV unless proven otherwise. Any bat-related injury (bite, scratch or mucosal exposure to bat saliva or neural tissue) should be notified immediately to the relevant public health unit - no matter how small the injury or how long ago it occurred. Human-to-human transmission of ABLV has not been reported but is theoretically possible. Standard infection control precautions should be employed when managing patients with suspected or confirmed ABLV infection.

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis

PubMed Central

Parrón, Ignasi; Planas, Caritat; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Jané, Mireia

2017-01-01

ABSTRACT Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2–98.6) for HAV vaccine and 98.3% (95% CI 91.3–99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases. PMID:27925847

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis.

PubMed

Parrón, Ignasi; Planas, Caritat; Godoy, Pere; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Torner, Nuria; Jané, Mireia; Domínguez, Angela

2017-02-01

Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2-98.6) for HAV vaccine and 98.3% (95% CI 91.3-99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.

Exploring the feasibility of engaging Traditional Birth Attendants in a prevention of mother to child HIV transmission program in Lilongwe, Malawi.

PubMed

Lippmann, Quinn Kerr; Mofolo, Innocent; Bobrow, Emily; Maida, Alice; Kamanga, Esmie; Pagadala, Nina; Martinson, Francis; van der Horst, Charles; Hosseinipour, Mina; Hoffman, Irving

2012-12-01

To investigate the willingness of Traditional Birth Attendants (TBAs) to provide single dose antiretroviral prophylaxis to infants born to mothers with HIV and the feasibility of providing the TBAs with antiretroviral medication. 2 focus groups with a total of 17 registered TBAs. Lilongwe, Malawi. TBAs were recruited by local health workers and participated in focus groups assessing their attitudes towards participation in a PMTCT program. TBAs were willing to participate in this prevention of mother-to-child HIV transmission (PMTCT) program and helped identify barriers to their participation. Given appropriate support and training, TBAs' participation in PMTCT programs could be an additional way to deliver medication to mothers and neonates who might otherwise miss crucial doses of medication.

The potential impact of pre-exposure prophylaxis for HIV prevention among men who have sex with men and transwomen in Lima, Peru: a mathematical modelling study.

PubMed

Gomez, Gabriela B; Borquez, Annick; Caceres, Carlos F; Segura, Eddy R; Grant, Robert M; Garnett, Geoff P; Hallett, Timothy B

2012-01-01

HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.

The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study

PubMed Central

Caceres, Carlos F.; Segura, Eddy R.; Grant, Robert M.; Garnett, Geoff P.; Hallett, Timothy B.

2012-01-01

Background HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. Methods and Findings We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. Conclusions A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary PMID:23055836

Prevention of mother-to-child transmission of human immunodeficiency virus among pregnant women using injecting drugs in Ukraine, 2000–10

PubMed Central

Thorne, Claire; Semenenko, Igor; Malyuta, Ruslan

2012-01-01

Aims To compare clinical status, mother-to-child transmission (MTCT) rates, use of prevention of (PMTCT) interventions and pregnancy outcomes between HIV-infected injecting drug users (IDUs) and non-IDUs. Design and setting Prospective cohort study conducted in seven human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Centres in Ukraine, 2000–10. Participants Pregnant HIV-infected women, identified before/during pregnancy or intrapartum, and their live-born infants (n = 6200); 1028 women followed post-partum. Measurements Maternal and delivery characteristics, PMTCT prophylaxis, MTCT rates, preterm delivery (PTD) and low birth weight (LBW). Findings Of 6200 women, 1111 (18%) reported current/previous IDU. The proportion of IDUs diagnosed with HIV before conception increased from 31% in 2000/01 to 60% in 2008/09 (P < 0.01). Among women with undiagnosed HIV at conception, 20% of IDUs were diagnosed intrapartum versus 4% of non-IDUs (P < 0.01). At enrolment, 14% of IDUs had severe/advanced HIV symptoms versus 6% of non-IDUs (P < 0.001). IDUs had higher rates of PTD and LBW infants than non-IDUs, respectively, 16% versus 7% and 22% versus 10% (P < 0.001). IDUs were more likely to receive no neonatal or intrapartum PMTCT prophylaxis compared with non-IDUs (OR 2.81, p < 0.001). MTCT rates were 10.8% in IDUs versus 5.9% in non-IDUs; IDUs had increased MTCT risk (adjusted odds ratio 1.32, P = 0.049). Fewer IDUs with treatment indications received HAART compared with non-IDUs (58% versus 68%, P = 0.03). Conclusions Pregnant human immunodeficiency virus-infected injecting drug users in Ukraine have worse clinical status, poorer access to prevention of mother-to-child transmission prophylaxis and highly active antiretroviral therapy, more adverse pregnancy outcomes and higher risk of mother-to-child transmission than non-injecting drug user women. PMID:21819473

A Mobile Health Strategy to Support Adherence to Antiretroviral Preexposure Prophylaxis.

PubMed

Fuchs, Jonathan D; Stojanovski, Kristefer; Vittinghoff, Eric; McMahan, Vanessa M; Hosek, Sybill G; Amico, K Rivet; Kouyate, Aminta; Gilmore, Hailey J; Buchbinder, Susan P; Lester, Richard T; Grant, Robert M; Liu, Albert Y

2018-03-01

Preexposure prophylaxis is a highly protective HIV prevention strategy, yet nonadherence can significantly reduce its effectiveness. We conducted a mixed methods evaluation of a mobile health intervention (iText) that utilized weekly bidirectional text or e-mail support messages to encourage preexposure prophylaxis (PrEP) adherence among participants in the multi-site iPrEx open-label extension study. A convenience sample of PrEP users from the San Francisco and Chicago sites participated in a 12-week pilot study. Fifty-six men who have sex with men were enrolled; a quarter of them were less than 30 years of age, 13% were black/African American, 11% were Latino, and most (88%) completed some college. Two-thirds opted for text message delivery. Of the 667 messages sent, only 1 individual requested support; initial nonresponse was observed in 22% and was higher among e-mail compared to text message recipients. Poststudy, a majority of participants would recommend the intervention to others, especially during PrEP initiation. Moreover, younger participants and men of color were more likely to report that they would use the iText strategy if it were available to them. Several participants commented that while they were aware that the messages were automated, they felt supported and encouraged that "someone was always there." Study staff reported that the intervention is feasible to administer and can be incorporated readily into clinic flow. A pre-post intervention regression discontinuity analysis using clinic-based pill counts showed a 50% reduction in missed doses [95% confidence interval (CI) 16-71; p = 0.008] and 77% (95% CI 33-92; p = 0.007) when comparing pill counts at quarterly visits just before and after iText enrollment. A mobile health intervention using weekly bidirectional messaging was highly acceptable and demonstrated promising effects on PrEP adherence warranting further evaluation for efficacy in a randomized controlled trial.

Ricky and Lucy: gender stereotyping among young Black men who have sex with men in the US Deep South and the implications for HIV risk in a severely affected population.

PubMed

Lichtenstein, Bronwen; Kay, Emma Sophia; Klinger, Ian; Mutchler, Matt G

2018-03-01

HIV disproportionately affects young Black men who have sex with men in the USA, with especially high rates in the Deep South. In this Alabama study, we interviewed 24 pairs of young Black men who have sex with men aged 19-24 and their close friends (n = 48) about sexual scripts, dating men and condom use. Three main themes emerged from the study: the power dynamics of 'top' and 'bottom' sexual positions for condom use; gender stereotyping in the iconic style of the 'I Love Lucy' show of the 1950s; and the sexual dominance of 'trade' men. Gender stereotyping was attributed to the cultural mores of Black families in the South, to the preferences of 'trade' men who exerted sexual and financial control and to internalised stigma relating to being Black, gay and marginalised. The findings suggest that HIV prevention education for young Black men who have sex with men is misguided if gendered power dynamics are ignored, and that funded access to self-protective strategies such as pre-exposure prophylaxis and post-exposure prophylaxis could reduce HIV risk for this severely affected population.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects

PubMed Central

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-01-01

ABSTRACT Aim: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Methods: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). Results: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Conclusions: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China. PMID:28121231

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

PubMed

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N’Djamena, Chad

PubMed Central

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N’Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general. PMID:28421186

Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial.

PubMed

Baeten, Jared M; Donnell, Deborah; Mugo, Nelly R; Ndase, Patrick; Thomas, Katherine K; Campbell, James D; Wangisi, Jonathan; Tappero, Jordan W; Bukusi, Elizabeth A; Cohen, Craig R; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kidoguchi, Lara; Coombs, Robert W; Hendrix, Craig; Marzinke, Mark A; Frenkel, Lisa; Haberer, Jessica E; Bangsberg, David; Celum, Connie

2014-11-01

Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP. We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov, number NCT00557245. 4410 (99·6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0·71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0·48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio [HR] 0·67, 95% CI 0·39-1·17; p=0·16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0·15, 95% CI 0·06-0·37; p<0·0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0·07, 0·02-0·23; p<0·0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups. These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women. Bill & Melinda Gates Foundation and US National Institutes of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of the impact of dental prophylaxis on the oral microbiota of dogs.

PubMed

Flancman, Rebecca; Singh, Ameet; Weese, J Scott

2018-01-01

Periodontal disease is one of the most commonly diagnosed oral diseases in dogs and can result from undisturbed dental plaque. Dental prophylaxis is a routinely practiced veterinary procedure, but its effects on both the plaque and oral microbiota is not fully understood. The objectives of this study were to evaluate the impact of dental prophylaxis on the composition of the supragingival plaque and composite oral microbiota in clinically healthy dogs and to determine if composite sampling could be used in lieu of sampling the plaque microbiota directly. Thirty dogs received a dental prophylaxis. Supragingival plaque and composite oral samples were collected just prior to, and one week after dental prophylaxis. A subsample of 10 dogs was followed, and additional samples were collected two and five weeks post-prophylaxis. The V4 region of the 16S rRNA gene was used for Illumina MiSeq next-generation sequencing. Results demonstrate that decreases in Treponema as well as increases in Moraxella and Neisseria distinguished the plaque pre- and one week post-prophylaxis timepoints (all P<0.05). Within the oral microbiota, the initially dominant Psychrobacter (20% relative abundance) disappeared one week later (P<0.0001), and Pseudomonas became the dominant taxon one week after treatment (80% relative abundance, P<0.0001). A rapid transition back towards the pre-dental prophylaxis microbiota by five weeks post-treatment was seen for both niches, suggesting the canine oral microbiota is resilient. Direct comparison of the two environments yielded striking differences, with complete separation of groups. Firmicutes (40%) and Spirochaetes (22%) predominated in the plaque while Proteobacteria (58%) was predominant in the oral microbiota. Greater richness was also seen in the plaque microbiota. This study reveals that prophylaxis had a profound impact on both the plaque and oral microbiota, and the longitudinal results help elucidate the pathophysiology of periodontal disease. The results suggest that oral swabs are a poor proxy for plaque samples and highlight the need to study specific oral niches.

Uptake and performance of prevention of mother-to-child transmission and early infant diagnosis in pregnant HIV-infected women and their exposed infants at seven health centres in Addis Ababa, Ethiopia.

PubMed

Girma, Marshet; Wendaferash, Rahel; Shibru, Hailu; Berhane, Yemane; Hoelscher, Michael; Kroidl, Arne

2017-06-01

To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's health services. Prospective observational study of HIV-positive pregnant mothers and their newborns attending PMTCT services at seven health centres in Addis Ababa. Women were recruited during antenatal care and followed up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV infant outcome were assessed. Turnaround times of HIV early infant diagnosis (EID) procedures were extracted from health registers. Of 494 women enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321 (65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0-4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post-partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0) and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID results were received for only 46.6% within 3 months of birth. High retention in PMTCT services, triple maternal ART and high infant nevirapine prophylaxis coverage were associated with low mother-to-child HIV transmission. Declining post-partum ART adherence and challenges of EID linkage require attention. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

PubMed Central

Vajpayee, M; Kaushik, S; Sreenivas, V; Wig, N; Seth, P

2005-01-01

CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts. PMID:16045738

Neutropenia in HIV-Infected Kenyan Women Receiving Triple Antiretroviral Prophylaxis to Prevent Mother-to-Child HIV Transmission Is Not Associated with Serious Clinical Sequelae.

PubMed

Iuliano, A Danielle; Weidle, Paul J; Brooks, John T; Masaba, Rose; Girde, Sonali; Ndivo, Richard; Ogindo, Paul; Omolo, Paul; Zeh, Clement; Thomas, Timothy K

2015-01-01

Absolute neutrophil counts (ANCs) are lower in East African adults. To assess the impact of lower ANCs, we reviewed data from HIV-infected Kenyan women receiving antiretroviral therapy antepartum and postpartum. The Kisumu Breastfeeding Study (KiBS) participants received an antiretroviral regimen from 34 weeks' gestation through 6 months postpartum. Measured ANCs and subsequent illnesses were reviewed. Adverse events (AEs) potentially attributable to neutropenia were identified, and ANCs were graded using the 2004 Division of AIDS table for Grading the Severity of AEs. Among 478 women with ≥1 postpartum ANC measured, 298 (62.1%) women met criteria for an AE (<1.3 × 10(9) cells/L). Of those, 38 (12.5%) women experienced a nonlife-threatening illness potentially attributable to neutropenia. More than half of KiBS women met criteria for neutropenia. The mild clinical experience of most participants with low ANCs supports that these values might be typical for this population and may not result in adverse clinical sequelae. © The Author(s) 2013.

Changing use of surgical antibiotic prophylaxis in Thika Hospital, Kenya: a quality improvement intervention with an interrupted time series design.

PubMed

Aiken, Alexander M; Wanyoro, Anthony K; Mwangi, Jonah; Juma, Francis; Mugoya, Isaac K; Scott, J Anthony G

2013-01-01

In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution.

Changing Use of Surgical Antibiotic Prophylaxis in Thika Hospital, Kenya: A Quality Improvement Intervention with an Interrupted Time Series Design

PubMed Central

Aiken, Alexander M.; Wanyoro, Anthony K.; Mwangi, Jonah; Juma, Francis; Mugoya, Isaac K.; Scott, J. Anthony G

2013-01-01

Introduction In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. Methods We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. Results From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. Conclusion Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution. PMID:24244390

Six-week follow-up after HIV-1 exposure: a position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy.

PubMed

Gaines, Hans; Albert, Jan; Axelsson, Maria; Berglund, Torsten; Gisslén, Magnus; Sönnerborg, Anders; Blaxhult, Anders; Bogdanovic, Gordana; Brytting, Maria; Carlander, Christina; Flamholc, Leo; Follin, Per; Haggar, Axana; Hagstam, Per; Johansson, Marcus; Navér, Lars; Persson Blom, Jenny; Samuelson, Agneta; Ström, Helena; Sundqvist, Martin; Svedhem Johansson, Veronica; Tegmark Wisell, Karin; Tegnell, Anders; Thorstensson, Rigmor

2016-02-01

In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.

Antiepileptic prophylaxis following severe traumatic brain injury within a military cohort.

PubMed

Cranley, Mark R; Craner, M; McGilloway, E

2016-04-01

Traumatic brain injury increases the risk of both early and late seizures. Antiepileptic prophylaxis reduces early seizures, but their use beyond 1 week does not prevent the development of post-traumatic epilepsy. Furthermore, prolonged prophylaxis exposes patients to side effects of the drugs and has occupational implications. The American Academy of Neurology recommends that antiepileptic prophylaxis should be started for patients with severe traumatic brain injury and discontinued after 1 week. An audit is presented here that investigates the use of prophylaxis in a cohort of military patients admitted to the UK Defence Medical Rehabilitation Centre (DMRC). Data were collected and analysed retrospectively from electronic and paper records between February 2009 and August 2012. The timing and duration of antiepileptic drug use and the incidence of seizures were recorded. During the study period, 52 patients with severe traumatic brain injury were admitted to the rehabilitation centre: 25 patients (48%) were commenced on prophylaxis during the first week following injury while 27 (52%) did not receive prophylaxis. Only one patient (2%) received prophylaxis for the recommended period of 1 week, 22 patients (42%) received prophylaxis for longer than 1 week with a mean duration of 6.2 months. Two patients (4%) had post-traumatic epilepsy and started on treatment at DMRC. The use of antiepileptic prophylaxis varies widely and is generally inconsistent with evidence-based guidance. This exposes some patients to a higher risk of early seizures and others to unnecessary use of antiepileptics. Better implementation of prophylaxis is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A Missed Opportunity for U.S. Perinatal Human Immunodeficiency Virus Elimination

PubMed Central

Fruhauf, Timothee; Coleman, Jenell S.

2018-01-01

OBJECTIVE To estimate the proportion of women at increased risk of sexual human immunodeficiency virus (HIV) acquisition during pregnancy in a high HIV incidence urban setting to identify those who may be eligible for pre-exposure prophylaxis. METHODS We conducted a retrospective cohort study of women who received prenatal care at a large academic center in 2012. Univariable analyses and multiple logistic regression models were built to identify correlates for pre-exposure prophylaxis eligibility. RESULTS Among 1,637 pregnant women, mean age was 27.6 years (SD 6.3), 59.7% were African American, and 56.0% were single. Based on the Centers for Disease Control and Prevention’s guidelines, more than 10% of women were at increased risk for HIV acquisition during pregnancy and eligible for pre-exposure prophylaxis. Younger [adjusted odds ratio (OR) 0.9/1-year increase, 95% CI 0.8–0.9], single (adjusted OR 2.4, 95% CI 1.2–4.8), African American women (adjusted OR 3.3, 95% CI 1.6–6.7) with higher parity (adjusted OR 1.3/one-child increase, 95% CI 1.1–1.5), and who smoked regularly during pregnancy (adjusted OR 1.8, 95% CI 1.0–3.0) had greater odds of being eligible for pre-exposure prophylaxis at any time during pregnancy. CONCLUSIONS Pregnancy is a vulnerable period during which some heterosexual women in urban settings have a high risk for HIV acquisition and stand to benefit from pre-exposure prophylaxis. PMID:28885420

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

PubMed Central

Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

2008-01-01

Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

Human Immunodeficiency Virus, Other Sexually Transmitted Infections, and Sexual and Reproductive Health in Lesbian, Gay, Bisexual, Transgender Youth.

PubMed

Wood, Sarah M; Salas-Humara, Caroline; Dowshen, Nadia L

2016-12-01

Lesbian, gay, bisexual, transgender (LGBT), and questioning youth represent a diverse population who are affected by many sexual health inequities, including increased risk for human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). To provide comprehensive sexual health care for LGBT youth, providers should set the stage with a nonjudgmental, respectful tone. Providers should be competent in recognizing symptoms of STIs and HIV and aware of the most up-to-date screening guidelines for LGBT youth. Sexual health visits should also focus on prevention, including safer sex practices, HIV pre-exposure and post-exposure prophylaxis, family planning, and immunization for hepatitis and human papillomavirus. Copyright © 2016 Elsevier Inc. All rights reserved.

Economic evaluation of HIV pre-exposure prophylaxis strategies: protocol for a methodological systematic review and quantitative synthesis.

PubMed

Thavorn, Kednapa; Kugathasan, Howsikan; Tan, Darrell H S; Moqueet, Nasheed; Baral, Stefan D; Skidmore, Becky; MacFadden, Derek; Simkin, Anna; Mishra, Sharmistha

2018-03-15

Pre-exposure prophylaxis (PrEP) with antiretrovirals is an efficacious and effective intervention to decrease the risk of HIV (human immunodeficiency virus) acquisition. Yet drug and delivery costs prohibit access in many jurisdictions. In the absence of guidelines for the synthesis of economic evaluations, we developed a protocol for a systematic review of economic evaluation studies for PrEP by drawing on best practices in systematic reviews and the conduct and reporting of economic evaluations. We aim to estimate the incremental cost per health outcome of PrEP compared with placebo, no PrEP, or other HIV prevention strategies; assess the methodological variability in, and quality of, economic evaluations of PrEP; estimate the incremental cost per health outcome of different PrEP implementation strategies; and quantify the potential sources of heterogeneity in outcomes. We will systematically search electronic databases (MEDLINE, Embase) and the gray literature. We will include economic evaluation studies that assess both costs and health outcomes of PrEP in HIV-uninfected individuals, without restricting language or year of publication. Two reviewers will independently screen studies using predefined inclusion criteria, extract data, and assess methodological quality using the Philips checklist, Second Panel on the Cost-effectiveness of Health and Medicines, and the International Society for Pharmacoeconomics and Outcomes Research recommendations. Outcomes of interest include incremental costs and outcomes in natural units or utilities, cost-effectiveness ratios, and net monetary benefit. We will perform descriptive and quantitative syntheses using sensitivity analyses of outcomes by population subgroups, HIV epidemic settings, study designs, baseline intervention contexts, key parameter inputs and assumptions, type of outcomes, economic perspectives, and willingness to pay values. Findings will guide future economic evaluation of PrEP strategies in terms of methodological and knowledge gaps, and will inform decisions on the efficient integration of PrEP into public health programs across epidemiologic and health system contexts. PROSPERO CRD42016038440 .

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options

PubMed Central

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

Introduction The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a “cleanser,” without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. Methods As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. Results The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Conclusions Women-controlled HIV prevention methods such as antiretroviral-based oral pre-exposure prophylaxis, vaginal gels, and vaginal rings are needed for HIV-negative widows who engage in sexual rituals related to widowhood. PMID:24973041

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options.

PubMed

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a "cleanser," without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Women-controlled HIV prevention methods such as antiretroviral-based oral pre-exposure prophylaxis, vaginal gels, and vaginal rings are needed for HIV-negative widows who engage in sexual rituals related to widowhood.

Enhancing HIV Pre-exposure, Prophylaxis Practices via an Educational Intervention.

PubMed

Newman, Rebecca; Katchi, Tasleem; Karass, Michael; Gennarelli, Melissa; Goutis, Jason; Kifayat, Alina; Solanki, Shantanu; Yandrapalli, Srikanth; Forman, Leanne; Nabors, Christopher

2018-04-20

Pre-exposure prophylaxis (PrEP) for HIV involves using antiretroviral drugs to prevent individuals at high risk from acquiring HIV infection. Most practicing primary care providers believe PrEP to be safe and effective, but less than half have prescribed or referred for PrEP. Attitudes and prescribing patterns among house officers have not been well described previously. Can an educational intervention enhance HIV PrEP practices among internal medicine house officers? This study relied on a pretest/posttest design. All categorical trainees at a medium-sized internal medicine program were offered a baseline survey to assess their knowledge on PrEP. This was followed by a PrEP-focused educational intervention and a postintervention survey. Likert scales captured perceptions regarding safety, effectiveness, barriers, factors that would promote PrEP use, potential side effects, impact on risk-taking behavior, and provider comfort level in assessing behavioral risks and in PrEP prescribing. Data were analyzed using descriptive statistics, Wilcoxon signed rank test, and the Kruskal-Wallis test. Significance was accepted for P < 0.05. Forty-eight (100%) trainees participated in the educational session, 45 (94%) in a preintervention survey, and 36 (75%) in a postintervention survey. Before PrEP training, 22% of respondents were unaware of PrEP, 78% believed PrEP was effective, 66% believed PrEP was safe, 62% had fair or poor awareness of side effects; 18% of residents had referred for or prescribed PrEP, and 31% believed they were likely to prescribe PrEP in the next 6 months. After the intervention, 94% of trainees believed PrEP was effective (P < 0.001), 92% believed PrEP was safe (P < 0.001), and two-thirds believed they were likely to prescribe PrEP in the next 6 months. Brief, focused training on HIV prevention promotes awareness, acceptance, and likelihood of prescribing PrEP by internal medicine trainees.

Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy.

PubMed

Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

2016-01-01

In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive "combination prevention" programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers' openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation.

Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy

PubMed Central

Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

2016-01-01

Background In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. Discussion The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive “combination prevention” programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. Conclusions The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers’ openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation. PMID:27760685

Women's experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa.

PubMed

van der Straten, Ariane; Stadler, Jonathan; Montgomery, Elizabeth; Hartmann, Miriam; Magazi, Busiswe; Mathebula, Florence; Schwartz, Katie; Laborde, Nicole; Soto-Torres, Lydia

2014-01-01

In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE. In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis. Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use. Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial participation and experiences with investigational products. Whether these impacted women's behaviors and may have contributed to ineffective trial results warrants further investigation.

Women’s Experiences with Oral and Vaginal Pre-Exposure Prophylaxis: The VOICE-C Qualitative Study in Johannesburg, South Africa

PubMed Central

van der Straten, Ariane; Stadler, Jonathan; Montgomery, Elizabeth; Hartmann, Miriam; Magazi, Busiswe; Mathebula, Florence; Schwartz, Katie; Laborde, Nicole; Soto-Torres, Lydia

2014-01-01

Background In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants’ experience of daily vaginal gel and oral tablet regimens in VOICE. Methods In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis. Results Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support–from partners and significant others–and the relationship tradeoffs entailed by using the products appear to discourage adequate product use. Conclusions Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women’s perceptions of trial participation and experiences with investigational products. Whether these impacted women’s behaviors and may have contributed to ineffective trial results warrants further investigation. PMID:24586534

HIV Pre-exposure Prophylaxis Program Implementation Using Intervention Mapping.

PubMed

Flash, Charlene A; Frost, Elizabeth L T; Giordano, Thomas P; Amico, K Rivet; Cully, Jeffrey A; Markham, Christine M

2018-04-01

HIV pre-exposure prophylaxis has been proven to be an effective tool in HIV prevention. However, numerous barriers still exist in pre-exposure prophylaxis implementation. The framework of Intervention Mapping was used from August 2016 to October 2017 to describe the process of adoption, implementation, and maintenance of an HIV prevention program from 2012 through 2017 in Houston, Texas, that is nested within a county health system HIV clinic. Using the tasks outlined in the Intervention Mapping framework, potential program implementers were identified, outcomes and performance objectives established, matrices of change objectives created, and methods and practical applications formed. Results include the formation of three matrices that document program outcomes, change agents involved in the process, and the determinants needed to facilitate program adoption, implementation, and maintenance. Key features that facilitated successful program adoption and implementation were obtaining leadership buy-in, leveraging existing resources, systematic evaluation of operations, ongoing education for both clinical and nonclinical staff, and attention to emergent issues during launch. The utilization of Intervention Mapping to delineate the program planning steps can provide a model for pre-exposure prophylaxis implementation in other settings. Copyright © 2018. Published by Elsevier Inc.

Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention.

PubMed

Mugwanya, Kenneth K; Baeten, Jared M

2016-01-01

Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.

Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

2015-01-01

Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials. © 2015 S. Karger AG, Basel.

Antiretroviral drug treatment of CNS HIV-1 infection.

PubMed

Yilmaz, Aylin; Price, Richard W; Gisslén, Magnus

2012-02-01

The advent of combination antiretroviral treatment has had a profound impact on CNS HIV infection and its clinical complications, but neurological impairment still occurs in patients on systemically effective combination therapy, and in some patients it may be important to consider antiretroviral drug entry and effects within the CNS. There are now data on the CNS exposure for most antiretroviral drugs. This review focuses on the CNS pharmacokinetics and pharmacodynamics of antiretroviral drugs in humans, and also discusses controversies in this field.

Possible rabies exposures in Peace Corps volunteers, 2011.

PubMed

Harvey, Kira; Jentes, Emily S; Charles, Myrna; Johnson, Katherine J; Petersen, Brett; Lamias, Mark J; Blanton, Jesse D; Sotir, Mark J; Brunette, Gary W

2014-05-01

We surveyed Peace Corps Medical Officers (PCMOs) to determine the frequency of and responses to possible rabies exposures of U.S. Peace Corps volunteers (PCVs). Surveys were sent to 56 PCMOs serving in countries with moderate or high rabies vaccine recommendations from the U.S. Centers for Disease Control and Prevention (CDC), of which 38 (68%) responded. Thirty-seven PCMOs reported that, of 4,982 PCVs, 140 (3%) experienced possible rabies exposures. Of these, 125 (89%) had previously received rabies vaccination, 129 (92%) presented with adequately cleansed wounds, and 106 (76%) were deemed to require and were given post-exposure prophylaxis (PEP). Of 35 respondents, 30 (86%) reported that rabies vaccine was always accessible to PCVs in their country within 24 hours. Overall, the Peace Corps is successful at preventing and treating possible rabies exposures. However, this study identified a few gaps in policy implementation. The Peace Corps should continue and strengthen efforts to provide education, preexposure vaccination, and PEP to PCVs.

Possible Rabies Exposures in Peace Corps Volunteers, 2011

PubMed Central

Harvey, Kira; Jentes, Emily S.; Charles, Myrna; Johnson, Katherine J.; Petersen, Brett; Lamias, Mark J.; Blanton, Jesse D.; Sotir, Mark J.; Brunette, Gary W.

2014-01-01

We surveyed Peace Corps Medical Officers (PCMOs) to determine the frequency of and responses to possible rabies exposures of U.S. Peace Corps volunteers (PCVs). Surveys were sent to 56 PCMOs serving in countries with moderate or high rabies vaccine recommendations from the U.S. Centers for Disease Control and Prevention (CDC), of which 38 (68%) responded. Thirty-seven PCMOs reported that, of 4,982 PCVs, 140 (3%) experienced possible rabies exposures. Of these, 125 (89%) had previously received rabies vaccination, 129 (92%) presented with adequately cleansed wounds, and 106 (76%) were deemed to require and were given post-exposure prophylaxis (PEP). Of 35 respondents, 30 (86%) reported that rabies vaccine was always accessible to PCVs in their country within 24 hours. Overall, the Peace Corps is successful at preventing and treating possible rabies exposures. However, this study identified a few gaps in policy implementation. The Peace Corps should continue and strengthen efforts to provide education, preexposure vaccination, and PEP to PCVs. PMID:24639304

Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

PubMed

Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-02-01

The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Modeling the Effects of Morphine on Simian Immunodeficiency Virus Dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaidya, Naveen K.; Ribeiro, Ruy M.; Perelson, Alan S.

Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses. Based on the small sample size Akaike information criterion, these models were inferior tomore » the new model based on changes in co-receptor expression. The model with morphine affecting co-receptor expression agrees well with the experimental data from simian immunodeficiency virus infections in morphine-addicted macaques. Our results show that morphine promotes a target cell subpopulation switch from a lower level of susceptibility to a state that is about 2-orders of magnitude higher in susceptibility to SIV infection. As a result, the proportion of target cells with higher susceptibility remains extremely high in morphine conditioning. Such a morphine-induced population switch not only has adverse effects on the replication rate, but also results in a higher steady state viral load and larger CD4 count drops. Moreover, morphine conditioning may pose extra obstacles to controlling viral load during antiretroviral therapy, such as pre-exposure prophylaxis and post infection treatments. In conclusion, this study provides, for the first time, a viral dynamics model, viral dynamics parameters, and related analytical and simulation results for SIV dynamics under drugs of abuse.« less

Modeling the Effects of Morphine on Simian Immunodeficiency Virus Dynamics

DOE PAGES

Vaidya, Naveen K.; Ribeiro, Ruy M.; Perelson, Alan S.; ...

2016-09-26

Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses. Based on the small sample size Akaike information criterion, these models were inferior tomore » the new model based on changes in co-receptor expression. The model with morphine affecting co-receptor expression agrees well with the experimental data from simian immunodeficiency virus infections in morphine-addicted macaques. Our results show that morphine promotes a target cell subpopulation switch from a lower level of susceptibility to a state that is about 2-orders of magnitude higher in susceptibility to SIV infection. As a result, the proportion of target cells with higher susceptibility remains extremely high in morphine conditioning. Such a morphine-induced population switch not only has adverse effects on the replication rate, but also results in a higher steady state viral load and larger CD4 count drops. Moreover, morphine conditioning may pose extra obstacles to controlling viral load during antiretroviral therapy, such as pre-exposure prophylaxis and post infection treatments. In conclusion, this study provides, for the first time, a viral dynamics model, viral dynamics parameters, and related analytical and simulation results for SIV dynamics under drugs of abuse.« less

[Evaluation of rabies post-exposure prophylaxis in humans injured by dogs and cats in the municipality of Jaboticabal, SP, from 2000 through 2006].

PubMed

Frias, Danila Fernanda Rodrigues; Lages, Sonia Luisa Silva; Carvalho, Adolorata Aparecida Bianco

2011-12-01

The present study aimed to evaluate rabies post-exposure prophylaxis (PEP) in humans in the municipality of Jaboticabal, São Paulo from 2000 through 2006. A descriptive and retrospective study was conducted by collecting data available in patient records. Vaccination costs were also calculated; 2,493 patients injured by animals received PEP, totaling R$ 179,105.14 and 7,108 doses; 2,184 (71.5%) out of the total reports were caused by dogs and cats clinically healthy at the moment of the attack. These animals remained sound throughout the 10-day observation period. The observation was conducted by the victim or by the owner. Considering animal observation and the epidemiological status of rabies in the municipality, all of these patients could have been dismissed from PEP treatment. Instead, only 464 were dismissed, meaning that 1,720 patients were unnecessarily vaccinated. An estimated 4,590 doses and R$114,420.81 could have been saved. In comparison with rates of other municipalities of the State of São Paulo and with the national mean, the number of PEP in Jaboticabal is very high and it became evident that management evaluated neither the health status of the animal nor the epidemiological status of the area for rabies. Permanent awareness and education of public health professionals with respect to rabies epidemiology and the need to perform correct observation of the aggressors are recommended. It is essential that medical and veterinary services be integrated to provide better assessment of cases and safer decisions on the institution of PEP.

The use of HIV post-exposure prophylaxis in forensic medicine following incidents of sexual violence in Hamburg, Germany: a retrospective study.

PubMed

Ebert, Julia; Sperhake, Jan Peter; Degen, Olaf; Schröder, Ann Sophie

2018-05-18

In Hamburg, Germany, the initiation of HIV post-exposure prophylaxis (HIV PEP) in cases of sexual violence is often carried out by forensic medical specialists (FMS) using the city's unique Hamburg Model. FMS-provided three-day HIV PEP starter packs include a combination of raltegravir and emtricitabine/tenofovir. This study aimed to investigate the practice of offering HIV PEP, reasons for discontinuing treatment, patient compliance, and whether or not potential perpetrators were tested for HIV. We conducted a retrospective study of forensic clinical examinations carried out by the Hamburg Department of Legal Medicine following incidents of sexual violence from 2009 to 2016. One thousand two hundred eighteen incidents of sexual violence were reviewed. In 18% of these cases, HIV PEP was initially prescribed by the FMS. HIV PEP indication depended on the examination occurring within 24 h after the incident, no/unknown condom use, the occurrence of ejaculation, the presence of any injury, and the perpetrator being from population at high risk for HIV. Half of the HIV PEP recipients returned for a reevaluation of the HIV PEP indication by an infectious disease specialist, and just 16% completed the full month of treatment. Only 131 potential perpetrators were tested for HIV, with one found to be HIV positive. No HIV seroconversion was registered among the study sample. Provision of HIV PEP by an FMS after sexual assault ensures appropriate and prompt care for victims. However, patient compliance and completion rates are low. HIV testing of perpetrators must be carried out much more rigorously.

[Reemergence of measles. Epidemic situation in the Valencian Community during the years 2011 and 2012].

PubMed

Rodrigo, Silvia Guiral; Calatrava, Rosana Guaita; Vicenta Rigo Medrano, M; Vidal, Miquel Amat; Martín-Sierra Balibrea, Miguel; Zarco, Isabel Huertas; Ramón, Jorge Roda; Cifre, Antonio Salazar; Morán, Francisco González

2014-02-01

Measles incidence declined until becomes a sporadic reporting and infrequent notification in the last decade. The reemergence of the disease reached 744 cases in 2012, a rate of 14.50×10(5) inhabitants. A classic design in Public Health Surveillance was performed: retrospective analysis of cumulative incidence and characteristics of the affected subjects. Those dates were in record linkage with Valencia Microbiology Network (RedMIVA). Finally, 976 cases of measles were confirmed in 2011-2012 epidemic period. Time-line distribution shows three waves with amplitude length on 12-15 weeks. Proportion of unvaccinated or unknown subjects came up to 85% of cases. 25 outbreaks were reported, 499 cases associated. In 7 of the 10 community outbreaks early cases were from Roma population unvaccinated. In the city of Valencia was applied post-exposure prophylaxis in 32 schools and was observed low coverage: between 63% and 77% in 8 schools and less than 50% in 4. Serum negative rate was 12.4% and we highlight the rate under 16 months: 44.8%. Cohorts of 20-59 years had negative rates between 13.5 to 5.9%. The origin of the epidemic was the importation of cases to a territory with inadequate immune protection against measles. Its impact and development was conditioned by previous immunization coverage, the social and ethnic pattern of different areas or quarters and the extensive application of post-exposure prophylaxis at school and family contacts of cases. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Determinants of health seeking behaviour following rabies exposure in Ethiopia.

PubMed

Beyene, T J; Mourits, M C M; Revie, C W; Hogeveen, H

2018-06-01

The objective of this study was to identify factors that determine medical treatment seeking behaviour following potential rabies exposure after being bitten by a suspected dog and the likelihood of compliance to receive sufficient doses of post-exposure prophylaxis after the visit to a health centre visit. A detailed survey based on case investigation was conducted on suspected rabid dog bite cases in three areas of Ethiopia. Two multivariable logistic regression models were created with a set of putative variables to explain treatment seeking and compliance outcomes. Based on the registered bite cases at each health centre and the set of unregistered bite cases derived by contact tracing, 655 bite victim cases were identified to have occurred between September 2013 and August 2014. Of these evaluated bite incidences, 465 cases were considered to have been caused by a potentially rabid dog. About 77% of these suspected rabid dog bite victims visited a health centre, while 57% received sufficient doses of PEP. The overall likelihood of seeking medical services following rabies exposure was higher for people bitten by dogs of unknown ownership, where the bite was severe, being bitten on the leg, spend of more than 100 USD per month and where the victim lived close to the nearest health centre, while the likelihood of receiving sufficient doses of PEP was sensitive to monthly spending and distance to health centre. However, the evaluated factors did only explain a part of the variation among the three districts. The district in which victims lived appeared to have a relevant influence on the likelihood of seeking medical treatment but did not improve the prediction on the likelihood of treatment compliance. Given the insights obtained from this study, improvements in the rural districts with regard to accessibility of post-exposure prophylaxis delivering health centres in shorter distance could improve health seeking behaviour. In addition, in rural districts, majority of exposed persons who seek medical treatment tend to comply with treatment regimen, indicating that the promotion of medical treatment through awareness creation campaigns could be beneficial. © 2018 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

Occupational risks and hepatitis B vaccination status of dental auxiliaries in Nigeria.

PubMed

Azodo, C C; Ehigiator, O; Ojo, M A

2010-01-01

To assess the occupational exposure to needlestick and sharps injuries and hepatitis B vaccination status among dental auxiliaries. A descriptive cross-sectional survey of 83 dental auxiliaries was conducted that included 12 technologists, 11 therapists, 53 nurses/surgical assistants, and 7 record officers. The survey included demography, history of needlestick and sharps injury, hepatitis B vaccination, knowledge and attitude towards HIV-infected patients, and the dental auxiliaries' information needs on HIV-related issues. Of the 83 dental auxiliaries, 34 (41%) had experienced needlestick and sharps injury in the last 12 months. At the time of the study, only 43 (51.8%) had been immunized against hepatitis B. 62 (74.7%) of the respondents thought that it was easier to contract HIV than hepatitis B through needlestick in a dental clinic. 21 (25.3%) would not assist dentists treating HIV-positive patients. However, 76 (91.6%), a majority, agreed that they needed more information on HIV-related issues, with 59 (71.1%) specifying a single area of need and 17 (20.5%) more than one area of need. The single areas of need specified in descending order were infection control (n = 22, 26.5%), HIV counseling (n = 12, 14.5%), oral manifestations of HIV/AIDS (n = 11, 13.3%), postexposure prophylaxis (n = 9, 10.8%), and antiretroviral therapy (n = 5, 6.0%). The data from this survey underscore the urgent need for educational interventions to encourage safe work practices. Hepatitis B vaccination, HIV-related knowledge and proper postexposure prophylaxis are needed to prevent occupational transmission of blood-borne viruses. Copyright 2010 S. Karger AG, Basel.

Adolescents and HIV clinical trials

PubMed Central

MacQueen, Kathleen M.; Karim, Quarraisha Abdool

2007-01-01

One quarter of HIV infections globally occur among young people 15-24 years of age and more than half of all new infections are to people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical and several promising methods are in development, including microbicides, vaccines, and pre-exposure prophylaxis (PREP) or the daily use of antiretrovirals to prevent the acquisition of HIV. There is widespread reluctance to enroll minors in such biomedical prevention trials due to concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted via the example of one rural South African community that has been particularly devastated by the HIV epidemic. PMID:17403499

Rectal Microbicide Development

PubMed Central

Dezzutti, Charlene

2014-01-01

The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmaco-dynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2–3 years. PMID:23612991

Characterizing the HIV Prevention and Care Continua in a Sample of Transgender Youth in the U.S

PubMed Central

Jadwin-Cakmak, Laura; White Hughto, Jaclyn M.; Martinez, Miguel; Salomon, Liz

2017-01-01

In the U.S., transgender and other gender minority (TG) youth are an at-risk group understudied in HIV prevention and treatment. This study sought to characterize the HIV prevention and care continua in a diverse sample of 181 sexually-active TG ages 16–24 years (mean age = 20.7 years; 76.8% trans feminine; 69.1% youth of color) recruited July–December 2015 in 14 U.S. cities. Overall, 30.9% reported living with HIV, of which 71.4% were on antiretroviral therapy (ART) and 55.0% were medication adherent; 65.6% were known to be virally suppressed. In multivariable models, medical gender affirmation was associated with lower odds of viral suppression. Medical gender affirmation and stigma in HIV care were each independently associated with elevated odds of having missed HIV care appointments. Among at-risk TG youth not living with HIV, only 8.2% had accessed pre-exposure prophylaxis (PrEP). Early biobehavioral prevention and treatment interventions are needed for TG youth. PMID:29138982

Modelling the UNAIDS 90-90-90 treatment cascade for gay, bisexual and other men who have sex with men in South Africa: using the findings of a data triangulation process to map a way forward.

PubMed

Scheibe, Andrew; Grasso, Michael; Raymond, Henry Fisher; Manyuchi, Albert; Osmand, Thomas; Lane, Tim; Struthers, Helen

2018-03-01

A data triangulation exercise was carried out between 2013 and 2015 to assess the HIV epidemic and response among gay, bisexual and other men who have sex with men (GBMSM) in South Africa. We used the findings to assess progress in achieving the UNAIDS 90-90-90 goals for GBMSM in the country. Three scenarios were developed using different GBMSM population factors (2.0, 3.5 and 5.0% of males aged ≥15) to estimate the population size, HIV prevalence of 13.2-49.5%, and 68% of GBMSM knowing their status. Due to data gaps, general population data were used as estimates of GBMSM on antiretroviral therapy (ART) and virologically suppressed (25.7 and 84.0%, respectively). The biggest gap is access to ART. To address the data gap we recommend developing data collection tools, indicators, and further quantification of HIV cascades. Targeted testing, linkage to services and scaled-up prevention interventions (including pre-exposure prophylaxis) are also required.

Ending AIDS as a public health threat by 2030: Scientific Developments from the 2016 INTEREST Conference in Yaoundé, Cameroon

PubMed Central

Hankins, Catherine A; Koulla-Shiro, Sinata; Kilmarx, Peter; Ferrari, Guido; Schechter, Mauro; Kane, Coumba Touré; Venter, François; Boucher, Charles AB; Ross, Anna-Laura; Zewdie, Debrework; Eholié, Serge Paul; Katabira, Elly

2017-01-01

The underpinning theme of the 2016 INTEREST Conference held in Yaoundé, Cameroon, 3–6 May 2016 was ending AIDS as a public health threat by 2030. Focused primarily on HIV treatment, pathogenesis and prevention research in resource-limited settings, the conference attracted 369 active delegates from 34 countries, of which 22 were in Africa. Presentations on treatment optimization, acquired drug resistance, care of children and adolescents, laboratory monitoring and diagnostics, implementation challenges, HIV prevention, key populations, vaccine and cure, hepatitis C, mHealth, financing the HIV response and emerging pathogens, were accompanied by oral, mini-oral and poster presentations. Spirited plenary debates on the UNAIDS 90-90-90 treatment cascade goal and on antiretroviral pre-exposure prophylaxis took place. Joep Lange career guidance sessions and grantspersonship sessions attracted early career researchers. At the closing ceremony, the Yaoundé Declaration called on African governments; UNAIDS; development, bilateral, and multilateral partners; and civil society to adopt urgent and sustained approaches to end HIV by 2030. PMID:28387654

Is prophylaxis required for delivery in women with factor VII deficiency?

PubMed Central

Baumann Kreuziger, Lisa M.; Morton, Colleen T.; Reding, Mark T.

2013-01-01

Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis. PMID:23607277

Is prophylaxis required for delivery in women with factor VII deficiency?

PubMed

Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

2013-11-01

Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

HIV-1 drug resistance in recently HIV-infected pregnant mother's naïve to antiretroviral therapy in Dodoma urban, Tanzania.

PubMed

Vairo, Francesco; Nicastri, Emanuele; Liuzzi, Giuseppina; Chaula, Zainab; Nguhuni, Boniface; Bevilacqua, Nazario; Forbici, Federica; Amendola, Alessandra; Fabeni, Lavinia; De Nardo, Pasquale; Perno, Carlo Federico; Cannas, Angela; Sakhoo, Calistus; Capobianchi, Maria Rosaria; Ippolito, Giuseppe

2013-09-21

HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

Barriers to innovation in human rabies prophylaxis and treatment: A causal analysis of insights from key opinion leaders and literature.

PubMed

van de Burgwal, L H M; Neevel, A M G; Pittens, C A C M; Osterhaus, A D M E; Rupprecht, C E; Claassen, E

2017-12-01

Rabies is an essentially 100% fatal, zoonotic disease, caused by Lyssaviruses. Currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (PrEP and PEP). Still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural Asia and Africa, due to the inaccessibility of prophylaxis and non-existence of treatment. Despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innovation receives relatively little attention compared to other neglected tropical diseases (NTDs). As such, the lag of innovation in human rabies prophylaxis and treatment cannot be explained by limited return on investment alone. Strategies countering rabies-specific innovation barriers are important for the acceleration of innovation in human rabies prophylaxis and treatment. Barriers throughout society, science, business development and market domains were identified through literature review and 23 semi-structured interviews with key opinion leaders worldwide. A subsequent root cause analysis revealed causal relations between innovation barriers and a limited set of root causes. Finally, prioritization by experts indicated their relative importance. Root causes, which are fundamental to barriers, were aggregated into four types: market and commercial, stakeholder collaboration, public health and awareness, and disease trajectory. These were found in all domains of the innovation process and thus are relevant for all stakeholders. This study identifies barriers that were not previously described in this specific context, for example the competition for funding between medical and veterinary approaches. The results stress the existence of barriers beyond the limited return on investment and thereby explain why innovation in human rabies medication is lagging behind NTDs with a lower burden of disease. A re-orientation on the full spectrum of barriers that hinder innovation in rabies prophylaxis and treatment is necessary to meet unmet societal and medical needs. © 2017 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

Interventions for preventing late postnatal mother-to-child transmission of HIV.

PubMed

Horvath, Tara; Madi, Banyana C; Iuppa, Irene M; Kennedy, Gail E; Rutherford, George; Read, Jennifer S

2009-01-21

Worldwide, mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV) represents the most common means by which children acquire HIV infection. Efficacious and effective interventions to prevent in utero and intrapartum transmission of HIV infection have been developed and implemented. However, a large proportion of MTCT of HIV occurs postnatally, through breast milk transmission. The objectives of this systematic review were to collate and assess the evidence regarding interventions to decrease late postnatal MTCT of HIV, and to determine the efficacy of such interventions in decreasing late postnatal MTCT of HIV, increasing overall survival, and increasing HIV-free survival. Electronic searches were undertaken using PubMed, EMBASE and other databases for 1980-2008. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative. Randomized clinical trials assessing the efficacy of interventions to prevent MTCT of HIV through breast milk were included in the analysis. Other trials and intervention cohort studies with relevant data also were included, but only when randomization was not feasible due to the nature of the intervention (i.e., infant feeding modality). Data regarding HIV infection status and vital status of infants born to HIV-infected women, according to intervention, were extracted from the reports of the studies. Six randomized clinical trials and one intervention cohort study were included in this review. Two trials addressed the issue of shortening the duration of (or eliminating) exposure to breast milk. In a trial of breastfeeding versus formula feeding, formula feeding was efficacious in preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but the mortality and malnutrition rates during the first two years of life were similar in the two groups. In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding around four months of age and those who continued breastfeeding. Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm. Efficacy for other vitamin supplements was not shown. An intervention cohort study evaluated the risk of MTCT according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids (hazard ratio = 10.87, p = 0.018) as well as higher 3-month mortality rates (hazard ratio = 2.06) among infants given non- breast milk feedings (instead of exclusive breastfeeding). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. One trial found that breastfeeding with zidovudine prophylaxis (transmission rate = 9.0%) was not as effective as formula feeding (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04). Breastfeeding with zidovudine prophylaxis and formula feeding had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended nevirapine prophylaxis demonstrated efficacy. In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second, nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of peripartum prophylaxis (10.6%) (p < 0.001). HIV-free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group. Complete avoidance of breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has significant associated morbidity (e.g., diarrheal morbidity if formula is prepared without clean water). If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life; and 2) chronic antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with zidovudine) are efficacious in preventing transmission.

How Stigma Surrounding the Use of HIV Preexposure Prophylaxis Undermines Prevention and Pleasure: A Call to Destigmatize "Truvada Whores".

PubMed

Calabrese, Sarah K; Underhill, Kristen

2015-10-01

Antiretroviral preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate [Truvada]) prevents HIV without penalizing sexual pleasure, and may even enhance pleasure (e.g., by reducing HIV-related anxiety). However, concern about sexual risk behavior increasing with PrEP use (risk compensation) and corresponding stereotypes of promiscuity may undermine PrEP's preventive potential. In this commentary, we review literature on sexual behavior change accompanying PrEP use, discuss risk compensation concerns and the "Truvada whore" stereotype as PrEP barriers, question the appropriateness of restricting PrEP access because of risk compensation, and consider sexual pleasure as a benefit of PrEP, an acceptable motive for seeking PrEP, and a core element of health. It is essential for science to trump stereotypes and sex-negative messaging in guiding decision-making affecting PrEP access and uptake.

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

PubMed Central

Tudor Car, Lorainne; Brusamento, Serena; Elmoniry, Hoda; van Velthoven, Michelle H. M. M. T.; Pape, Utz J.; Welch, Vivian; Tugwell, Peter; Majeed, Azeem; Rudan, Igor; Car, Josip; Atun, Rifat

2013-01-01

Background The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries. Methods and Findings We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30–100%) and 81% (range 26–100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22–99%) and 60% (range 19–100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44–100%) of infants were tested for HIV and 11% (range 3–18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis. Conclusion The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed. PMID:23483887

The uptake of integrated perinatal prevention of mother-to-child HIV transmission programs in low- and middle-income countries: a systematic review.

PubMed

Tudor Car, Lorainne; Brusamento, Serena; Elmoniry, Hoda; van Velthoven, Michelle H M M T; Pape, Utz J; Welch, Vivian; Tugwell, Peter; Majeed, Azeem; Rudan, Igor; Car, Josip; Atun, Rifat

2013-01-01

The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries. We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30-100%) and 81% (range 26-100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22-99%) and 60% (range 19-100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44-100%) of infants were tested for HIV and 11% (range 3-18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis. The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed.

Zika vaccines and therapeutics: landscape analysis and challenges ahead.

PubMed

Wilder-Smith, Annelies; Vannice, Kirsten; Durbin, Anna; Hombach, Joachim; Thomas, Stephen J; Thevarjan, Irani; Simmons, Cameron P

2018-06-06

Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome. Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.

[Tetanus prophylaxis after an injury; check the need for vaccination and immunoglobulin].

PubMed

te Wierik, Margreet J M; Hahné, Susan J M; van Ooik, Paula C; van Lier, Ans M C; Swaan, Corien M

2013-01-01

Tetanus can occur after an injury and is caused by the exotoxin of Clostridium tetani. Characteristics of generalised tetanus include spasms in the back and other muscles, trismus, risus sardonicus and difficulty in breathing caused by laryngospasms. Vaccination through the National Vaccination Programme of the Netherlands has resulted in 94% of the population being protected against tetanus; certain groups, however, have a low rate of vaccination. In the Netherlands, 5 patients were reported to have generalised tetanus in 2011. This figure is relatively high in comparison with previous years. Of these 5 patients, 3 did not receive post-exposure-prophylaxis (PEP) after their injuries, or received it incompletely. PEP may be comprised of 1 or more vaccinations with the tetanus toxoid and/or the administration of tetanus immunoglobulin. Patients who have sustained an injury should be evaluated in accordance with the guideline 'Tetanus' by the Landelijke Coördinatie Infectieziekten (National Coordination Centre for communicable disease control), and to assess whether PEP is indicated.

[Consensus Statement by GeSIDA/National AIDS Plan Secretariat on antiretroviral treatment in adults infected by the human immunodeficiency virus (Updated January 2013)].

PubMed

2013-11-01

This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the GeSIDA/National AIDS Plan Secretariat (Grupo de Estudio de Sida and the Secretaría del Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations and the evidence which support them are based on a modification of the criteria of Infectious Diseases Society of America. cART is recommended in patients with symptoms of HIV infection, in pregnant women, in serodiscordant couples with high risk of transmission, in hepatitisB co-infection requiring treatment, and in HIV nephropathy. cART is recommended in asymptomatic patients if CD4 is <500cells/μl. If CD4 are >500cells/μl cART should be considered in the case of chronic hepatitisC, cirrhosis, high cardiovascular risk, plasma viral load >100.000 copies/ml, proportion of CD4 cells <14%, neurocognitive deficits, and in people aged >55years. The objective of cART is to achieve an undetectable viral load. The first cART should include 2 reverse transcriptase inhibitors (RTI) nucleoside analogs and a third drug (a non-analog RTI, a ritonavir boosted protease inhibitor, or an integrase inhibitor). The panel has consensually selected some drug combinations, for the first cART and specific criteria for cART in acute HIV infection, in tuberculosis and other HIV related opportunistic infections, for the women and in pregnancy, in hepatitisB or C co-infection, in HIV-2 infection, and in post-exposure prophylaxis. These new guidelines update previous recommendations related to first cART (when to begin and what drugs should be used), how to monitor, and what to do in case of viral failure or adverse drug reactions. cART specific criteria in comorbid patients and special situations are similarly updated. Copyright © 2013 Elsevier España, S.L. All rights reserved.

[From Evidence to Health Policy Making: Pre-Exposure Prophylaxis for HIV Prevention].

PubMed

Ko, Nai-Ying

2016-12-01

Pre-exposure prophylaxis (PrEP), in combination with traditional prevention strategies (such as condom use, voluntary HIV counseling and testing, and treatment for sexually transmitted infections), has been shown to effectively prevent HIV infection. As of September 2015, the World Health Organization recommends that people at substantial risk of HIV infection should be offered PrEP as an additional prevention choice, as part of comprehensive prevention. This article introduces how to apply a systematic review using the methodology of Grading of Recommendations Assessment, Development and Evaluation (GRADE) to write clinical guidelines. With support from the Taiwan Centers for Disease Control, the Taiwan AIDS Society published clinical guidelines for oral pre-exposure prophylaxis in Taiwan. Nurses are responsible to apply evidence-based knowledge and to use their professional influence to shape health policies related to HIV prevention.

Antiretroviral treatment is associated with iron deficiency in HIV-infected Malawian women that is mitigated with supplementation, but is not associated with infant iron deficiency during 24 weeks of exclusive breastfeeding

PubMed Central

Widen, Elizabeth M; Bentley, Margaret E; Chasela, Charles S; Kayira, Dumbani; Flax, Valerie L; Kourtis, Athena P; Ellington, Sascha R; Kacheche, Zebrone; Tegha, Gerald; Jamieson, Denise J; van der Horst, Charles M; Allen, Lindsay H; Shahab-Ferdows, Setareh; Adair, Linda S

2015-01-01

Objective In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (via fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. Methods The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial conducted in Lilongwe, Malawi from 2004-2010. HIV-infected mothers (CD4>200 cells/ul) and their infants were randomly assigned to 28-week interventions: maternal-LNS/maternal-ARV (n=424), maternal-LNS/infant-ARV (n=426), maternal-LNS (n=334), maternal-ARV (n=425), infant-ARV (n=426), or control (n=334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n=537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR) and ferritin were tested with linear and Poisson regression. Results In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR>8.3 mg/L) (Risk ratio (RR): 3.1, p<0.01), but not in ARV-treated mothers receiving LNS (p=0.17). LNS without ARVs, was not associated with iron deficiency or anemia (p>0.1). In subsample infants, interventions were not associated with impaired iron status (all p-values>0.1). Conclusions Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not appear to influence infant iron status; however, extended use needs to be evaluated. PMID:25723140

Healthcare worker safety: a vital component of surgical capacity development in low-resource settings.

PubMed

Petroze, Robin T; Phillips, Elayne K; Nzayisenga, Albert; Ntakiyiruta, Georges; Calland, J Forrest

2012-01-01

A disparate number of occupational exposures to bloodborne pathogens occur in low-income countries where disease prevalence is high and healthcare provider-per-population ratios are low. In an effort to highlight the important role of healthcare worker safety in surgical capacity building in Rwanda, we measured self-reported presence of safety materials and compliance with personal protective equipment in the operating theatre as part of a nationwide survey to characterize emergency and essential surgical capacity in all government hospitals. We surveyed 44 hospitals. While staff report general availability of safe disposal of sharps and hazardous waste, presence of and compliance with eye protection was lacking. Staff were cognizant of prevention measures such as double-gloving and 'safe receptacles', as well as hospital policies for post-exposure prophylaxis for HIV following needlesticks, but there was little awareness of hepatitis exposure. Healthcare worker safety should be a key component of hospital-level surgical capacity.

Post-discharge compliance to venous thromboembolism prophylaxis in high-risk orthopaedic surgery: results from the ETHOS registry.

PubMed

Bergqvist, David; Arcelus, Juan I; Felicissimo, Paulo

2012-02-01

Venous thromboembolism (VTE) risk persists for several weeks following high-risk orthopaedic surgery (HROS). The ETHOS registry evaluated post-operative VTE prophylaxis prescribed, and actual VTE prophylaxis received, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in HROS patients. We performed a subanalysis of ETHOS to assess patient compliance with ACCP-adherent prophylaxis after discharge and the factors predicting poor compliance. Consecutive patients undergoing hip fracture surgery, total hip arthroplasty, or knee arthroplasty were enrolled at discharge from 161 centres in 17 European countries if they had received adequate in-hospital VTE prophylaxis. Data on prescribed and actual prophylaxis received were obtained from hospital charts and patient post-discharge diaries. Good compliance was defined as percentage treatment intake ≥80% with no more than two consecutive days without treatment. A total of 3,484 patients (79.4%) received ACCP-adherent anticoagulant prescription at discharge and 2,999 (86.0%) had an evaluable patient diary. In total, 87.7% of evaluable patients were compliant with prescribed treatment after discharge. The most common reason for non-compliance (33.4%) was "drug was not bought". Injection of treatment was not a barrier to good compliance. Main factors affecting compliance related to purchase of and access to treatment, patient education, the person responsible for administering injections, country, and type of hospital ward at discharge. Within our study population, patient compliance with ACCP-adherent thromboprophylaxis prescribed at discharge was good. Improvements in patient education and prescribing practices at discharge may be important in further raising compliance levels in high-risk orthopaedic surgery patients.

Mother-to-child transmission of HIV and its predictors among HIV-exposed infants at Bamenda Regional Hospital, Cameroon.

PubMed

Fondoh, Victor N; Mom, Njong A

2017-01-01

Mother-to-child transmission (MTCT) of HIV, has been a major global public health burden. Despite the use of antiretroviral prophylaxis by HIV-positive pregnant women and their infants, safe obstetric practice and safe infant feeding habits in the prevention of MTCT of HIV, the prevalence of HIV among HIV-exposed infants is still high in Cameroon. Our objectives were to determine the prevalence, assess the predictors and determine the effect of combination antiretroviral therapy (cART) on MTCT of HIV at the regional hospital in Bamenda, Cameroon. This was a retrospective study. Secondary data from 877 HIV-exposed infants aged ≤ 72 weeks were extracted from the records between January 2008 and December 2014. The predictors and effect of cART on MTCT of HIV were analysed using a multivariable logistic regression model and risk analysis, respectively. Out of 877 HIV-exposed infants, 62 were positive for HIV, giving a prevalence of 7.1%. Maternal antiretroviral intervention and infant age group were statistically significant predictors of MTCT of HIV. HIV-positive mothers who were on cART were 2.49 times less likely to transmit HIV than those who were not on cART. In order to reduce the prevalence of HIV among HIV-exposed infants, maternal antiretroviral intervention should be targeted and the use of cART by HIV-positive pregnant women should be encouraged.

Safety of Oral Tenofovir Disoproxil Fumarate-Based Pre-Exposure Prophylaxis for HIV Prevention

PubMed Central

Mugwanya, Kenneth K.; Baeten, Jared M.

2016-01-01

Introduction Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. Areas covered We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability and side effects, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. Expert opinion TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP’s substantial reduction in the risk of HIV infection. PMID:26634852

Lack of Doxycycline Antimalarial Prophylaxis Impact on Staphylococcus aureus Tetracycline Resistance

PubMed Central

Mende, Katrin; Beckius, Miriam L.; Zera, Wendy C.; Yu, Xin; Li, Ping; Tribble, David R.; Murray, Clinton K.

2016-01-01

There is concern that susceptibility of Staphylococcus aureus to tetracyclines may decrease due to use of antimalarial prophylaxis (doxycycline). We examined characteristics related to tetracycline resistance, including doxycycline exposure, in S. aureus isolates collected via admission surveillance swabs and inpatient clinical cultures from United States military personnel injured during deployment (June 2009-January 2012). Tetracycline class resistance was determined using antimicrobial susceptibility testing. The first S. aureus isolate from 168 patients were analyzed, of which 38 (23%) isolates were resistant to tetracyclines (class). Tetracycline-resistant isolates had a higher proportion of resistance to clindamycin (p=0.019) compared to susceptible isolates. There was no significant difference in tetracycline resistance between isolates collected from patients with and without antimalarial prophylaxis; however, significantly more isolates had tet(M) resistance genes in the doxycycline exposure group (p=0.031). Despite 55% of the patients receiving doxycycline as antimalarial prophylaxis, there was no association with resistance to tetracyclines. PMID:27460426

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

PubMed

Haberer, Jessica E; Baeten, Jared M; Campbell, James; Wangisi, Jonathan; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Psaros, Christina; Safren, Steven A; Ware, Norma C; Thomas, Katherine K; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie; Bangsberg, David R

2013-01-01

Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

Brucella melitensis infection following military duty in Iraq.

PubMed

Bechtol, D; Carpenter, L R; Mosites, E; Smalley, D; Dunn, J R

2011-11-01

Brucellosis is a common zoonotic disease worldwide; however, few cases are reported in the US. Brucella melitensis infections are primarily acquired via consumption of high-risk foods or travel to endemic areas. We describe a case of B. melitensis infection in a Tennessee soldier following deployment in Iraq. Initial symptoms included knee and back pain. Culture of an aspirate of the left sacroiliac joint yielded B. melitensis. Genetic analysis indicated that this isolate came from the Middle East. Investigation of laboratory workers identified risky exposures and positive serology prompting post-exposure prophylaxis. Military personnel and other travellers should be advised to reduce risk regarding food consumption and animal contact in endemic areas. Additionally, medical providers should remain vigilant for non-endemic zoonoses among recent travellers. © 2011 Blackwell Verlag GmbH.

Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study.

PubMed

Smith, Jennifer A; Anderson, Sarah-Jane; Harris, Kate L; McGillen, Jessica B; Lee, Edward; Garnett, Geoff P; Hallett, Timothy B

2016-07-01

Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine. With current information, a strategic approach in which limited resources are used to maximise prevention impact would focus on strengthening the scale-up of existing interventions, while pursuing a workable vaccine and developing other approaches that can be used if further scale-up of existing interventions is limited. Bill & Melinda Gates Foundation. Copyright © 2016 Smith et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Cumulative Antiretroviral Exposure Measured in Hair Is Not Associated With Measures of HIV Persistence or Inflammation Among Individuals on Suppressive ART.

PubMed

Gandhi, Monica; Gandhi, Rajesh T; Stefanescu, Andrei; Bosch, Ronald J; Cyktor, Joshua C; Horng, Howard; Louie, Alexander; Phung, Nhi; Eron, Joseph J; Hogg, Evelyn; Macatangay, Bernard J C; Hensel, Christopher; Fletcher, Courtney V; Mellors, John W; McMahon, Deborah K

2018-06-20

Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation.

Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda

PubMed Central

Mayer, Kenneth H.

2014-01-01

Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

A randomized noninferiority trial of standard versus enhanced risk reduction and adherence counseling for individuals receiving post-exposure prophylaxis following sexual exposures to HIV.

PubMed

Roland, Michelle E; Neilands, Torsten B; Krone, Melissa R; Coates, Thomas J; Franses, Karena; Chesney, Margaret A; Kahn, James S; Martin, Jeffrey N

2011-07-01

The National HIV/AIDS Strategy proposes to scale-up post-exposure prophylaxis (PEP). Intensive risk reduction and adherence counseling appear to be effective but are resource intensive. Identifying simpler interventions that maximize the HIV prevention potential of PEP is critical. A randomized noninferiority study comparing 2 (standard) or 5 (enhanced) risk reduction counseling sessions was performed. Adherence counseling was provided in the enhanced arm. We measured changes in unprotected sexual intercourse acts at 12 months, compared with baseline; HIV acquisition; and PEP adherence. Outcomes were stratified by degree of baseline risk. We enrolled 457 individuals reporting unprotected intercourse within 72 h with an HIV-infected or at-risk partner. Participants were 96% male and 71% white. There were 1.8 and 2.3 fewer unprotected sex acts in the standard and enhanced groups. The maximum potential risk difference, reflected by the upper bound of the 95% confidence interval, was 3.9 acts. The difference in the riskier subset may have been as many as 19.6 acts. The incidence of HIV seroconversion was 2.9% and 2.6% among persons randomized to standard and enhanced counseling, respectively, with a maximum potential difference of 3.4%. The absolute and maximal HIV seroconversion incidence was 9.9% and 20.4% greater in the riskier group randomized to standard, compared with enhanced, counseling. Adherence outcomes were similar, with noninferiority in the lower risk group and concerning differences among the higher-risk group. Risk assessment is critical at PEP initiation. Standard counseling is only noninferior for individuals with lower baseline risk; thus, enhanced counseling should be targeted to individuals at higher risk. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

A Study to Determine the Optimal Frequency for Conducting Periodic Dental Examinations, Recruit Needs. Part II.

DTIC Science & Technology

1980-06-01

06 NO V16 - POST ENDO .04 .02 .04 NO .14 .06 NO V17 - PROPHYLAXIS .92 .95 .92 NO .87 .91 NO V18 - SCALING .74 .88 .76 YES .79 .76 NO V19 - PERIO TX .05... ENDO M .04 .25 .02 .16 F 0 0 0 0 V17 - PROPHYLAXIS M .92 .26 .94 .22 F .86 .35 1.00 0 V18 - SCALING M .74 .43 .87 .33 F .60 .50 1.00 0 V19 - PERIO TX M...1033 0 .0863 NO V16 - POST ENDO .1268 .0714 .1176 NO V17 - PROPHYLAXIS .3405 .3524 .3424 NO VIB - SCALING .1400 .1674 .1445 YES V19 - PERIO TX .3439

Immunogenicity and Safety of Four Different Dosing Regimens of Anthrax Vaccine Adsorbed for Post-Exposure Prophylaxis for Anthrax in Adults

PubMed Central

Bernstein, David I.; Jackson, Lisa; Patel, Shital M.; El Sahly, Hana M.; Spearman, Paul; Rouphael, Nadine; Rudge, Thomas L.; Hill, Heather; Goll, Johannes B.

2014-01-01

Background Strategies to implement post exposure prophylaxis (PEP) in case of an anthrax bioterror event are needed. To increase the number of doses of vaccine available we evaluated reducing the amount of vaccine administered at each of the vaccinations, and reducing the number of doses administered. Methods Healthy male and non-pregnant female subjects between the ages of 18 and 65 were enrolled and randomized 1:1:1:1 to one of four study arms to receive 0.5 mL (standard dose) of vaccine subcutaneously (SQ) at: A) days 0, 14; B) days 0 and 28; C) days 0, 14, and 28; or D) 0.25 ml at days 0, 14, and 28. A booster was provided on day 180. Safety was assessed after each dose. Blood was obtained on days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84, 100, 180, and 201 and both Toxin Neutralizing antibody and anti-PA IgG antibody measured. Results Almost all subjects developed some local reactions with 46% to 64% reported to be of moderate severity and 3.3% severe during the primary series. Vaccine groups that included a day 14 dose induced a ≥4 fold antibody rise in more subjects on days 21, 28 and 35 than the arm without a day 14 dose. However, schedules with a full day 28 dose induced higher peak levels of antibody that persisted longer. The half dose regimen did not induce antibody as well as the full dose study arms. Conclusion Depending on the extent of the outbreak, effectiveness of antibiotics and availability of vaccine, the full dose 0, 28 or 0, 14, 28 schedules may have advantages. PMID:25239484

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

PubMed

Solomon, Marc M; Schechter, Mauro; Liu, Albert Y; McMahan, Vanessa M; Guanira, Juan V; Hance, Robert J; Chariyalertsak, Suwat; Mayer, Kenneth H; Grant, Robert M

2016-03-01

Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

Immunogenicity and safety of four different dosing regimens of anthrax vaccine adsorbed for post-exposure prophylaxis for anthrax in adults.

PubMed

Bernstein, David I; Jackson, Lisa; Patel, Shital M; El Sahly, Hana M; Spearman, Paul; Rouphael, Nadine; Rudge, Thomas L; Hill, Heather; Goll, Johannes B

2014-10-29

Strategies to implement post exposure prophylaxis (PEP) in case of an anthrax bioterror event are needed. To increase the number of doses of vaccine available we evaluated reducing the amount of vaccine administered at each of the vaccinations, and reducing the number of doses administered. Healthy male and non-pregnant female subjects between the ages of 18 and 65 were enrolled and randomized 1:1:1:1 to one of four study arms to receive 0.5 mL (standard dose) of vaccine subcutaneously (SQ) at: (A) days 0, 14; (B) days 0 and 28; (C) days 0, 14, and 28; or (D) 0.25 mL at days 0, 14, and 28. A booster was provided on day 180. Safety was assessed after each dose. Blood was obtained on days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84, 100, 180, and 201 and both Toxin Neutralizing antibody and anti-PA IgG antibody measured. Almost all subjects developed some local reactions with 46-64% reported to be of moderate severity and 3.3% severe during the primary series. Vaccine groups that included a day 14 dose induced a ≥ 4 fold antibody rise in more subjects on days 21, 28, and 35 than the arm without a day 14 dose. However, schedules with a full day 28 dose induced higher peak levels of antibody that persisted longer. The half dose regimen did not induce antibody as well as the full dose study arms. Depending on the extent of the outbreak, effectiveness of antibiotics and availability of vaccine, the full dose 0, 28 or 0, 14, 28 schedules may have advantages. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epidemiological characteristics and post-exposure prophylaxis of human rabies in Chongqing, China, 2007-2016.

PubMed

Qi, Li; Su, Kun; Shen, Tao; Tang, Wenge; Xiao, Bangzhong; Long, Jiang; Zhao, Han; Chen, Xi; Xia, Yu; Xiong, Yu; Xiao, Dayong; Feng, Liangui; Li, Qin

2018-01-03

According to the global framework of eliminating human rabies, China is responding to achieve the target of zero human death from dog-mediated rabies by 2030. Chongqing is the largest municipality directly under central government in China. We described the epidemiological characteristics and post-exposure prophylaxis (PEP) of human rabies in this area, in order to provide a reliable epidemiology basis for further control and prevention of human rabies. The most updated epidemiological data for human rabies cases from 2007 to 2016 in Chongqing were collected from the National Disease Reporting Information System. A standardized questionnaire was applied to the human rabies cases or family members of cases as proxy to investigate the PEP situation. A total of 809 fatal human rabies cases were reported in Chongqing from 2007 to 2016. There was a trend of gradual annual decline about number of cases from 2007 to 2013, followed by stable levels until 2016. Rabies was mostly reported in summer and autumn; a majority of cases were noted in farmers (71.8%), especially in males (65.3%). The cases aged 35-74 and 5-14 years old accounted for 83.8% of all the cases. We collected information of 548 human rabies cases' rabies exposure and PEP situation. Of those, 95.8% of human rabies cases were victims of dog bites or scratch, and 53.3% of these dogs were identified as stray dogs. Only 4.0% of the domestic dogs were reported to have been vaccinated previously. After exposure, 87.8% of the 548 human rabies cases did not seek any medical services. Further investigation showed that none of the 548 cases received timely and properly standardized PEP. Human rabies remains a major public health problem in Chongqing, China. Dogs are the main reservoir and source of human rabies infection. Unsuccessful control of canine rabies and inadequate PEP of cases might be the main factors leading to the serious human rabies epidemic in this area. An integrated "One Health" approach should be encouraged and strengthened in this area; with combined effort it would be possible to achieve the elimination of human rabies in the expected date.

Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure.

PubMed

Lundberg, B E; Davidson, A J; Burman, W J

2000-11-10

To determine the relative contribution of patient non-adherence, provider failure to prescribe prophylaxis, and drug failure to the continued occurrence of Pneumocystis carinii pneumonia (PCP), and to determine correlates of non-adherence. Retrospective case-control study. Patients with confirmed or presumptive PCP from May 1995 to September 1997 who had at least 6 months of prior HIV care (cases) were compared to controls matched for initial CD4 cell count and date of initial HIV care. The incidence of PCP declined by 85% in the 28 months of the study. Of the 118 cases of PCP identified, 59 (50%) were in HIV care for > 6 months prior to PCP diagnosis. In a multivariate logistic regression model, risk factors for PCP among patients in HIV care were patient non-adherence [odds ratio (OR), 12.4; 95% confidence interval (CI), 6.4-23.5], use of prophylaxis other than trimethoprim-sulfamethoxazole (OR, 27.0; 95% CI, 13.8-52.9), and absence of antiretroviral use (OR, 7.5; 95% CI, 4.5-12.5). Provider non-adherence occurred in one out of 59 cases (2%), and five out of 106 controls (5%). Of the patients who developed PCP on prophylaxis, 18 cases (30%) appeared due to drug failure; there were no cases of apparent drug failure among patients on trimethoprim-sulfamethoxazole. In multivariate analysis, non-adherence was more common among patients of non-white race, those with a history of injecting drug use, and those with active substance abuse or psychiatric illness. Patient non-adherence was the most common reason for the occurrence of PCP among patients in HIV care; provider non-adherence was uncommon. Drug failure occurred only among patients on prophylaxis other than trimethoprim-sulfamethoxazole.

[Diagnosis, prophylaxis and treatment of central nervous system involvement by non-Hodgkin lymphoma in HIV-infected patients].

PubMed

Miralles, Pilar; Berenguer, Juan; Ribera, Josep-Maria

2010-09-18

With the widespread use of highly active antiretroviral therapy (HAART) the incidence of systemic non-Hodgkin lymphoma (NHL) in patients infected with the Human Immunodeficiency Virus (HIV) has declined. HAART has also modified the clinical manifestations of these tumors, with a lower frequency of involvement of the central nervous system (CNS). Currently, the frequency of meningeal involvement at the time of diagnosis of NHL in HIV-infected patients varies between 3% and 5%. These figures are similar to those observed among immunocompetent hosts. The diagnosis of meningeal lymphoma relies in clinical findings, imaging techniques, and cerebrospinal fluid (CSF) examination. Flow cytometry is a diagnostic technique with a higher sensitivity and specificity than conventional cytology for the diagnosis of meningeal lymphoma. However, flow cytometry is not yet considered to be the gold standard for this purpose. Until recently, most experts recommended neuromeningeal prophylaxis for all HIV-infected patients with aggressive NHL. However, at present this prophylaxis is recommended only in patients with higher risk of CNS relapse according to different sites of involvement, stage and histological subtype. There are different regimens of prophylaxis and treatment for meningeal lymphoma. The drugs most commonly used for this purpose are methotrexate and cytosine arabinoside. However, there are other alternatives such as liposomal cytosine arabinoside that requires fewer spinal taps for drug administration and whose results are very promising. In summary, in the context of an effective HAART, HIV infected patients with NHL have a frequency of CNS involvement by lymphoma similar to that found among immunocompetent hosts. Consequently, indications and regimens for CNS prophylaxis in HIV-infected patients with NHL should not be different than those employed in the general population. Universal CNS prophylaxis should be reserved for the few patients unable to receive an effective HAART. Copyright © 2009 Elsevier España, S.L. All rights reserved.

Cost effectiveness of prophylaxis for opportunistic infections in AIDS. An overview and methodological discussion.

PubMed

Freedberg, K A; Paltiel, A D

1998-08-01

Dramatic progress has recently been made in defining the pathogenesis and treatment of HIV infection. For the first time in the history of the AIDS epidemic, clinicians have at their disposal an understanding of the replication kinetics of HIV, reliable assays to measure viral load, an increasing number of effective agents to suppress viral replication and to reverse the process of immune system destruction, and a range of options for the treatment and prophylaxis of most of the major opportunistic infections in HIV disease. These remarkable advances are not without their costs, however. New antiretroviral therapies and opportunistic infection prophylaxis regimens impose considerable financial strain on public and private budgets for HIV patient care. They force decision-makers to confront a variety of competing considerations, including issues of length and quality of life, the risks of adverse effects and toxicities, and the dangers of promoting resistance. Questions regarding the continued appropriateness and efficiency of opportunistic infection prevention have prompted increased interest in studies of the cost effectiveness of HIV patient care. In this article, we reviewed the literature on the economic evaluation of prophylaxis for HIV-related complications. Section 1 provides background on recent scientific and clinical advances. Section 2 reviews the state-of-the-art understanding of the cost effectiveness of prophylaxis against specific opportunistic infections. Section 3 broadens the discussion to consider the more general question of optimal allocation of prophylaxis resources across competing opportunistic infections. In Section 4, we briefly examined the influence of cost-effectiveness evaluations on the development and refinement of clinical guidelines for HIV-related opportunistic infection prevention in the US. Section 5 presents some of the methodological challenges that arise in applying the methods of cost-effectiveness analysis to the particular case of opportunistic infection prevention in AIDS. We close, in Section 6, with a comment on directions for further research.

Cost-effectiveness of culture-guided antimicrobial prophylaxis for the prevention of infections after prostate biopsy.

PubMed

Li, Chi-Kong; Tong, Brian C Y; You, Joyce H S

2016-02-01

Clinical findings suggest that the use of rectal culture-guided antibiotic prophylaxis reduces the infection rate following transrectal ultrasound-guided prostate biopsy (TRUSBx). A decision-analytic model was designed to compare the outcomes of TRUSBx performed with (rectal culture-guided group) and without (standard ciprofloxacin prophylaxis) rectal swab culture-guided antimicrobial prophylaxis in Hong Kong. The post-biopsy infection rate, infection-related costs, quality-adjusted life years (QALYs) lost for infection, and incremental cost per QALY saved (ICER) were assessed. Model inputs were retrieved from local epidemiology data and the medical literature. A sensitivity analysis was performed to test the robustness of the model results. Base-case analysis showed that the infection rate in the culture-guided group was reduced from 2.42% to 0.23% and saved 0.0002 QALYs, with a lower cost (USD 31.4 versus USD 55.6) (USD 1=HKD 7.8). The number needed to screen to prevent an infection episode was 45.7. The hospital days avoided per 100 patients using culture-guided prophylaxis was 7.08 days. The relative effectiveness of culture-guided antimicrobial prophylaxis versus standard prophylaxis in carriers and non-carriers of FQ-resistant rectal flora were identified as potential influencing factors. In 10000 Monte Carlo simulations, ICERs of the culture-guided group were below the willingness-to-pay threshold 99.12% of the time. Using rectal culture-guided antimicrobial prophylaxis for men undergoing TRUSBx appears to be a cost-saving strategy to avert post-biopsy infection and QALY loss in Hong Kong. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Efficient post-exposure prophylaxis against rabies by applying a four-dose DNA vaccine intranasally.

PubMed

Tesoro Cruz, Emiliano; Feria Romero, Iris Angélica; López Mendoza, Juan Gabriel; Orozco Suárez, Sandra; Hernández González, Rafael; Favela, Francisco Blanco; Pérez Torres, Armando; José Alvaro Aguilar Setién

2008-12-09

We tested two post-exposure prophylaxes (PEPs) for rabies in laboratory animals; one was a traditional antirabies vaccine for humans via intramuscular route (IM), and the other was a DNA vaccine administered by intranasal route (IN). In contrast to The World Health Organization's recommended five-dose PEP, we gave only four doses without hyper-immune antirabies sera, making the PEP more rigorous. All animals were challenged with challenge virus strain (CVS); 16h later, PEP was applied. All animals that received the PEP with DNA/IN survived, and 87% of the rabbits and 80% of the mice that received the PEP with traditional antirabies vaccine/IM survived. Negative controls succumbed to infection. The expression of G protein was detected in the NALT, cerebellum, cerebral cortex (neocortex), cerebellum and hippocampus, mainly in the glial cells (microglia) and microvessels. On the other hand, plasmid construct was detected in brain and its mRNA expression in medium and posterior encephalon. The efficiency of this DNA/IN PEP is probably due to the early expression of the antigen in the brain stimulating the immune system locally.

Perspectives on HIV Pre- and Post- Exposure Prophylaxes (PrEP and PEP) among Female and Male Sex Workers in Mombasa, Kenya: Implications for Integrating Biomedical Prevention into Sexual Health Services

PubMed Central

Restar, Arjee J.; Tocco, Jack Ume; Mantell, Joanne E.; Lafort, Yves; Gichangi, Peter; Masvawure, Tsitsi B; Chabeda, Sophie Vusha; Sandfort, Theo G. M.

2017-01-01

Pre- and post-exposure prophylaxis (PrEP and PEP) can reduce the risk of HIV acquisition, yet often are inaccessible to and underutilized by most-vulnerable populations, including sex workers in sub-Saharan Africa. Based on in-depth interviews with 21 female and 23 male HIV-negative sex workers in Mombasa, Kenya, we found that awareness and knowledge of PrEP and PEP were low, although willingness to use both was high. Participants felt PrEP would be empowering and give added protection against infection, although some expressed concerns about side effects. Despite its availability, few knew about PEP and even fewer had used it, but most who had would use it again. Sex workers valued confidentiality, privacy, trustworthiness, and convenient location in health services and wanted thorough HIV/STI assessments. These findings suggest the importance of situating PrEP and PEP within sex worker-friendly health services and conducting outreach to promote these biomedical prevention methods for Kenyan sex workers. PMID:28467163

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

PubMed Central

La Rosa, Corinna; Limaye, Ajit P.; Krishnan, Aparna; Blumstein, Gideon; Longmate, Jeff; Diamond, Don J.

2012-01-01

Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune-priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R−) of a SOT from a seropositive donor (D+). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is overexpressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D+R− patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D+R− patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which however showed exhaustion phenotypes. PMID:21672050

Bilateral oblique facial clefts and extremity anomaly in an infant after intrauterine efavirenz exposure and review of its teratogenic risk.

PubMed

Shanske, Alan L

2012-09-10

Congenital anomalies may be caused by genetic or environmental factors or a combination of both. Oblique facial clefts are very rare congenital deformities. The occurrence of facial clefts and an extremity anomaly suggests a common underlying cause. Lateral oro-ocular clefts do not occur along normal developmental planes and may be part of the amnion disruption complex sequence. Our objective was to report a case of this very event, which also followed an unusual intrauterine exposure and review the literature on the teratogenic risk of efavirenz. We report a case of amniotic rupture sequence after fetal HIV and antiretroviral exposure. Teratogenic exposure has been rarely reported and never after antiretroviral exposure. By reporting and registering more cases, we will be able to better assess the risks such medications pose to the developing fetus. The publication of a single case report has the potential to contribute to our knowledge of the significance of prenatal exposure to antiretrovirals and other medications for common HIV-associated disorders. It also generates a hypothesis that can be tested with further clinical data, animal models and epidemiologic studies.

An economic evaluation of conception strategies for heterosexual serodiscordant couples where the male partner is HIV-positive.

PubMed

Letchumanan, Michelle; Coyte, Peter C; Loutfy, Mona

2015-01-01

To conduct an economic evaluation of the three commonly used interventions that reduce sexual HIV transmission when an HIV-negative female aims to conceive with an HIV-positive male on combination antiretroviral therapy (condomless sex restricted to timed ovulation [CS], sperm washing with intrauterine insemination [SW] and condomless sex restricted to timed ovulation with pre-exposure prophylaxis [CS-PrEP]). As SW and CS-PrEP are only privately available for pregnancy planning for this population in Canada, this study was conducted to inform policy decisions concerning potential public health insurance coverage, as well as to inform fertility counselling in settings with adequate combination antiretroviral therapy access globally. We developed a cohort Markov model with a lifetime horizon and used the perspective of Ontario's Ministry of Health (MOH). Input parameters were drawn from literature, the MOH's Schedule of Benefits and a time trade-off questionnaire designed for this study. Outcome measures included quality-adjusted life-years and incremental cost-effectiveness. Costs and benefits were discounted at annual rates of 3%. Costs were reported in Canadian 2013 dollars and an exchange rate of 1 USD to 1.066 CND was applied where necessary. Sensitivity analysis assessed the uncertainty of model parameters. The base case analysis found that CS-PrEP and SW were each more costly and less effective at conception than CS. The results were robust in the sensitivity analysis and suggest that CS is the dominant conception strategy in this population. Neither CS-PrEP nor SW represent better value for money relative to CS as a conception option for HIV-discordant couples with positive male partners. Based on these findings, CS-PrEP and SW cannot be recommended for public-funding in developed countries.

Patterns and Correlates of PrEP Drug Detection among MSM and Transgender Women in the Global iPrEx Study

PubMed Central

Liu, Albert; Glidden, David V.; Anderson, Peter L.; Amico, K.R.; McMahan, Vanessa; Mehrotra, Megha; Lama, Javier R.; MacRae, John; Hinojosa, Juan Carlos; Montoya, Orlando; Veloso, Valdilea G.; Schechter, Mauro; Kallas, Esper G.; Chariyalerstak, Suwat; Bekker, Linda-Gail; Mayer, Kenneth; Buchbinder, Susan; Grant, Robert

2014-01-01

Background Adherence to pre-exposure prophylaxis (PrEP) is critical for efficacy. Antiretroviral concentrations are an objective measure of PrEP use and correlate with efficacy. Understanding patterns and correlates of drug detection can identify populations at risk for non-adherence and inform design of PrEP adherence interventions. Methods Blood antiretroviral concentrations were assessed among active-arm participants in iPrEx, a randomized, placebo-controlled trial of emtricitabine/tenofovir in men who have sex with men (MSM) and transgender women in 6 countries. We evaluated rates and correlates of drug detection among a random sample of 470 participants at week 8 and a longitudinal cohort of 303 participants through 72 weeks of follow-up. Results Overall, 55% (95% CI 49–60%) of participants tested at week 8 had drug detected. Drug detection was associated with older age and varied by study site. In longitudinal analysis, 31% never had drug detected, 30% always had drug detected, and 39% had an inconsistent pattern. Overall detection rates declined over time. Drug detection at some or all visits was associated with older age; indices of sexual risk, including condomless receptive anal sex; and responding "don't know" to a question about belief of PrEP efficacy (0–10 scale). Conclusions Distinct patterns of study-product use were identified, with a significant proportion demonstrating no drug detection at any visit. Research literacy may explain greater drug detection among populations having greater research experience, such as older MSM in the US. Greater drug detection among those reporting highest-risk sexual practices is expected to increase the impact and cost-effectiveness of PrEP. PMID:25230290

Risk Perception, Sexual Behaviors, and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study.

PubMed

Storholm, Erik D; Volk, Jonathan E; Marcus, Julia L; Silverberg, Michael J; Satre, Derek D

2017-08-01

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) taken as pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk of HIV infection, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20-35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants' risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient subcategories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

Can treatment-based HIV prevention curb the epidemic among gay and other men who have sex with men? A narrative synthesis of increasing evidence for moderating and countervailing effects.

PubMed

de Wit, John B F; Adam, Philippe C G

2014-07-01

As HIV epidemics among gay and other men who have sex with men (GMSM) persist worldwide, the importance of novel prevention approaches is recognised. Evidence that antiretroviral therapy (ART) can decrease the likelihood of infection is informing emerging HIV prevention approaches, encompassing early initiation of treatment as prevention by people living with HIV and use of antiretroviral drugs as pre-exposure prophylaxis for people presumed to be uninfected. Despite widespread excitement, robust evidence of the beneficial effects of ART-based HIV prevention for GMSM remains limited. Also, theoretical models project widely varying effects of ART-based prevention on the future course of HIV epidemics among GMSM, drawing attention to the possible moderating role of differences in the achievements of local HIV responses and the critical importance of sustained protective sexual practices into the future. Ecological analyses and simulations of ongoing epidemics in major gay communities illustrate that the preventive effects of ART in many settings are being offset by increased sexual risk-taking, as reflected in stable or increasing HIV infection rates. Also, the effects of scaling up HIV testing and treatment among GMSM in settings that are often considered prime examples of the success of ART-based prevention may be levelling as 'scope for improvement' diminishes. ART-based approaches further extend the HIV prevention toolkit and substantially increase people's options to protect themselves and others. The future impact of ART-based prevention on HIV epidemics among GMSM ultimately depends on whether heralded responses offset, attenuate or compound the ongoing social and behavioural changes that drive increased sexual risk.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

PubMed

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

2015-01-01

Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention

PubMed Central

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R.; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J.; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

2015-01-01

Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. Methods ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Results Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18–45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22–31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. Conclusions African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention. PMID:26061040

Use of a risk scoring tool to identify higher-risk HIV-1 serodiscordant couples for an antiretroviral-based HIV-1 prevention intervention.

PubMed

Irungu, Elizabeth M; Heffron, Renee; Mugo, Nelly; Ngure, Kenneth; Katabira, Elly; Bulya, Nulu; Bukusi, Elizabeth; Odoyo, Josephine; Asiimwe, Stephen; Tindimwebwa, Edna; Celum, Connie; Baeten, Jared M

2016-10-17

Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) reduce HIV-1 transmission within heterosexual HIV-1 serodiscordant couples. Prioritizing couples at highest HIV-1 transmission risk for ART and PrEP would maximize impact and minimize costs. The Partners Demonstration Project is an open-label, delivery study of integrated PrEP and ART for HIV-1 prevention among high risk HIV-1 serodiscordant couples in Kenya and Uganda. We evaluated the feasibility of using a validated risk score that weighs a combination of easily measurable factors (age, children, marital status, male circumcision status, condom use, plasma HIV-1 levels) to identify couples at highest risk for HIV-1 transmission for enrollment. Couples scoring ≥5 met the risk score eligibility criteria. We screened 1694 HIV-1 serodiscordant couples and enrolled 1013. Of the screened couples, 1331 (78.6 %) scored ≥5 (with an expected incidence >3 % per year) and 76 % of these entered the study. The median age of the HIV-1 uninfected partner was 29 years [IQR 26, 36] and 20 % were <25 years of age. The HIV-1 uninfected partner was male in 67 % of partnerships, 33 % of whom were uncircumcised, 57 % of couples had no children, and 65 % reported unprotected sex in the month prior to enrollment. Among HIV-1 infected partners, 41 % had plasma viral load >50,000 copies/ml. A risk scoring tool identified HIV-1 serodiscordant couples for a demonstration project of PrEP and ART with high HIV-1 risk. The tool may be feasible for research and public health settings to maximize efficiency and minimize HIV-1 prevention costs.

Mother-to-child transmission of HIV and its predictors among HIV-exposed infants at Bamenda Regional Hospital, Cameroon

PubMed Central

Mom, Njong A.

2017-01-01

Background Mother-to-child transmission (MTCT) of HIV, has been a major global public health burden. Despite the use of antiretroviral prophylaxis by HIV-positive pregnant women and their infants, safe obstetric practice and safe infant feeding habits in the prevention of MTCT of HIV, the prevalence of HIV among HIV-exposed infants is still high in Cameroon. Objective Our objectives were to determine the prevalence, assess the predictors and determine the effect of combination antiretroviral therapy (cART) on MTCT of HIV at the regional hospital in Bamenda, Cameroon. Methods This was a retrospective study. Secondary data from 877 HIV-exposed infants aged ≤ 72 weeks were extracted from the records between January 2008 and December 2014. The predictors and effect of cART on MTCT of HIV were analysed using a multivariable logistic regression model and risk analysis, respectively. Results Out of 877 HIV-exposed infants, 62 were positive for HIV, giving a prevalence of 7.1%. Maternal antiretroviral intervention and infant age group were statistically significant predictors of MTCT of HIV. HIV-positive mothers who were on cART were 2.49 times less likely to transmit HIV than those who were not on cART. Conclusion In order to reduce the prevalence of HIV among HIV-exposed infants, maternal antiretroviral intervention should be targeted and the use of cART by HIV-positive pregnant women should be encouraged. PMID:29435421

Rabies Post-Exposure Prophylaxis in the Philippines: Health Status of Patients Having Received Purified Equine F(ab')2 Fragment Rabies Immunoglobulin (Favirab)

PubMed Central

Quiambao, Beatriz P.; DyTioco, Hazel Z.; Dizon, Ruby M.; Crisostomo, Marilyn E.; Laot, Thelma M.; Teuwen, Dirk E.

2008-01-01

Background Recommended treatment for severe rabies exposure in unvaccinated individuals includes wound cleaning, administration of rabies immunoglobulins (RIG), and rabies vaccination. We conducted a survey of rabies treatment outcomes in the Philippines. Methods This was a case series involving 7,660 patients (4 months to 98 years of age) given purified equine RIG (pERIG) at the Research Institute for Tropical Medicine (Muntinlupa, Philippines) from July 2003 to August 2004 following Category II or III exposures. Data on local and systemic adverse reactions (AR) within 28 days and biting animal status were recorded; outcome data were obtained by telephone or home visit 6–29 months post-exposure. Results Follow-up data were collected for 6,464 patients. Of 151 patients with laboratory-confirmed rabies exposure, 143 were in good health 6–48 months later, seven could not be contacted, and one 4-year-old girl died. Of 16 deaths in total, 14 were unrelated to rabies exposure or treatment. Two deaths were considered PEP failures: the 4-year old girl, who had multiple deep lacerated wounds from a rabid dog of the nape, neck, and shoulders requiring suturing on the day of exposure, and an 8-year-old boy who only received rabies PEP on the day of exposure. Conclusions This extensive review of outcomes in persons with Category III exposure shows the recommended treatment schedule at RITM using pERIG is well tolerated, while survival of 143 laboratory-confirmed rabies exposures confirms the intervention efficacy. Two PEP intervention failures demonstrate that sustained education and training is essential in rabies management. PMID:18509475

Characterization of rabies virus from a human case in Nepal.

PubMed

Pant, G R; Horton, D L; Dahal, M; Rai, J N; Ide, S; Leech, S; Marston, D A; McElhinney, L M; Fooks, A R

2011-04-01

Rabies is endemic throughout most of Asia, with the majority of human cases transmitted by domestic dogs (Canis familiaris). Here, we report a case of rabies in a 12-year-old girl in the Lalitpur district of Nepal that might have been prevented by better public awareness and timely post-exposure prophylaxis. Molecular characterization of the virus showed 100% identity over a partial nucleoprotein gene sequence to previous isolates from Nepal belonging to the 'arctic-like' lineage of rabies virus. Sequence analysis of both partial nucleoprotein and glycoprotein genes showed differences in consensus sequence after passage in vitro but not after passage in vivo.

[Efficacy of the treatment and secondary antifungal prophylaxis in AIDS-related histoplasmosis. Experience at the Francisco J. Muñiz Infectious Diseases Hospital in Buenos Aires].

PubMed

Negroni, Ricardo; Messina, Fernando; Arechavala, Alicia; Santiso, Gabriela; Bianchi, Mario

Classic histoplasmosis is a systemic endemic mycosis due to Histoplasma capsulatum var. capsulatum. A significant reduction in the morbidity and mortality of AIDS-related histoplasmosis has been observed since the introduction of highly active antiretroviral therapy (HAART) and secondary antifungal prophylaxis. The aim of this study was to determine the current state of prognosis and treatment response of HIV-positive patients with histoplasmosis in the Francisco J. Muñiz Infectious Diseases Hospital in Buenos Aires City. A retrospective study was conducted using the demographic, clinical, immunological and treatment data of 80 patients suffering from AIDS-related histoplasmosis. Of the 80 cases studied 65 were male, the median age was 36 years, with 73.7% of the patients being drug addicts, 82.5% of the patients was not receiving HAART at diagnosis, and 58.7% of the cases had less than 50 CD4+ cells/μl at the beginning of the treatment. The initial phase of treatment consisted of intravenous amphotericin B and/or oral itraconazole for 3 months, with 78.7% of the cases showing a good clinical response. Only 26/63 patients who were discharged from hospital continued with the follow-up of the HAART, secondary prophylaxis with itraconazole or amphotericin B. Secondary prophylaxis was stopped after more than one year of HAART if the patients were asymptomatic, had two CD 4 + cell counts greater than 150cells/μl, and undetectable viral loads. No relapses were observed during a two-year follow up after prophylaxis was stopped. The treatment of histoplasmosis in HIV-positive patients was effective in 78.8% of the cases. The combination of HAART and secondary antifungal prophylaxis is safe, well tolerated, and effective. The low adherence of patients to HAART and the lack of laboratory kits for rapid histoplasmosis diagnosis should be addressed in the future. The usefulness of primary antifungal prophylaxis for cryptococcosis and histoplasmosis HIV-positive patients should be studied. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women

PubMed Central

Baeten, J.M.; Palanee-Phillips, T.; Brown, E.R.; Schwartz, K.; Soto-Torres, L.E.; Govender, V.; Mgodi, N.M.; Kiweewa, F. Matovu; Nair, G.; Mhlanga, F.; Siva, S.; Bekker, L.-G.; Jeenarain, N.; Gaffoor, Z.; Martinson, F.; Makanani, B.; Pather, A.; Naidoo, L.; Husnik, M.; Richardson, B.A.; Parikh, U.M.; Mellors, J.W.; Marzinke, M.A.; Hendrix, C.W.; van der Straten, A.; Ramjee, G.; Chirenje, Z.M.; Nakabiito, C.; Taha, T.E.; Jones, J.; Mayo, A.; Scheckter, R.; Berthiaume, J.; Livant, E.; Jacobson, C.; Ndase, P.; White, R.; Patterson, K.; Germuga, D.; Galaska, B.; Bunge, K.; Singh, D.; Szydlo, D.W.; Montgomery, E.T.; Mensch, B.S.; Torjesen, K.; Grossman, C.I.; Chakhtoura, N.; Nel, A.; Rosenberg, Z.; McGowan, I.; Hillier, S.

2016-01-01

BACKGROUND Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P = 0.05) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P = 0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, −133 to 31; P = 0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096.) PMID:26900902

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

PubMed

Baeten, Jared M; Palanee-Phillips, Thesla; Brown, Elizabeth R; Schwartz, Katie; Soto-Torres, Lydia E; Govender, Vaneshree; Mgodi, Nyaradzo M; Matovu Kiweewa, Flavia; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Pather, Arendevi; Naidoo, Logashvari; Husnik, Marla; Richardson, Barbra A; Parikh, Urvi M; Mellors, John W; Marzinke, Mark A; Hendrix, Craig W; van der Straten, Ariane; Ramjee, Gita; Chirenje, Zvavahera M; Nakabiito, Clemensia; Taha, Taha E; Jones, Judith; Mayo, Ashley; Scheckter, Rachel; Berthiaume, Jennifer; Livant, Edward; Jacobson, Cindy; Ndase, Patrick; White, Rhonda; Patterson, Karen; Germuga, Donna; Galaska, Beth; Bunge, Katherine; Singh, Devika; Szydlo, Daniel W; Montgomery, Elizabeth T; Mensch, Barbara S; Torjesen, Kristine; Grossman, Cynthia I; Chakhtoura, Nahida; Nel, Annalene; Rosenberg, Zeda; McGowan, Ian; Hillier, Sharon

2016-12-01

Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

Development of model infectious disease protocols for fire and EMS personnel.

PubMed

Miller, Nancy L; Gudmestad, Tom; Eisenberg, Mickey S

2005-01-01

To develop model infectious disease exposure plans for emergency medical services agencies in King County, Washington. All fire departments in King County, Washington, were surveyed to determine their pathogen exposure policies. After these agencies were surveyed, model response plans were developed for both bloodborne and airborne pathogen exposure. Twenty-four of the 35 fire departments in King County submitted infectious disease exposure policies. There was diversity among the plans, and not all were deemed able to provide prophylaxis in a timely fashion. Based on this lack of uniformity among response plans, model response plans were developed for bloodborne and airborne infectious disease pathogens. Great variety was present throughout the exposure plans currently in use throughout King County, Washington. Model plans would likely universalize response to pathogen exposure and help to ensure prompt and appropriate postexposure prophylaxis.

Role of tenofovir alafenamide (TAF) in the treatment and prophylaxis of HIV and HBV infections.

PubMed

De Clercq, Erik

2018-07-01

Tenofovir (TFV) is the cornerstone of the treatment and prophylaxis of HIV infections. It has been routinely used in its prodrug form TDF (tenofovir disoproxil fumarate) combined with emtricitabine ((-)FTC) and other antiretroviral agents. TDF has now been replaced by TAF (tenofovir alafenamide) which allows better uptake by the lymphoid tissue. In combination with elvitegravir (E), cobicistat (C), emtricitabine (F), TAF can be advocated as an STR (single tablet regimen, Genvoya®) for the treatment of HIV infections. In this combination, E and C may in the future be replaced by bictegravir. The prophylaxis of HIV infection is momentarily based upon Truvada®, the combination of F with TDF, which in the future may also be replaced by TAF. TAF (Vemlidy®) has also replaced TDF (Viread®) for the treatment of hepatitis B virus (HBV) infections. Both TDF and TAF offer little or no risk for virus-drug resistance. As compared to TDF, TAF limits the risk for nephrotoxicity and loss of bone mineral density. What remains to be settled, however, before the universal use of TAF could be recommended, is its safety during pregnancy and its applicability in the treatment of tuberculosis, in combination with rifampicin. Copyright © 2017 Elsevier Inc. All rights reserved.

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

PubMed Central

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Risk of Drug Resistance Among Persons Acquiring HIV Within a Randomized Clinical Trial of Single- or Dual-Agent Preexposure Prophylaxis

PubMed Central

Lehman, Dara A.; Baeten, Jared M.; McCoy, Connor O.; Weis, Julie F.; Peterson, Dylan; Mbara, Gerald; Donnell, Deborah; Thomas, Katherine K.; Hendrix, Craig W.; Marzinke, Mark A.; Frenkel, Lisa; Ndase, Patrick; Mugo, Nelly R.; Celum, Connie; Overbaugh, Julie; Matsen, Frederick A.; Celum, Connie; Baeten, Jared M.; Donnell, Deborah; Coombs, Robert W.; Frenkel, Lisa; Hendrix, Craig W.; Marzinke, Mark A.; Lingappa, Jairam; McElrath, M. Juliana; Fife, Kenneth; Were, Edwin; Tumwesigye, Elioda; Ndase, Patrick; Katabira, Elly; Katabira, Elly; Ronald, Allan; Bukusi, Elizabeth; Cohen, Craig; Wangisi, Jonathan; Campbell, James; Tappero, Jordan; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Mugo, Nelly Rwamba; Campbell, James; Tappero, Jordan; Wangisi, Jonathan

2015-01-01

Background. Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use. Methods. Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing. Results. Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment. Conclusions. These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF. PMID:25587020

Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

PubMed

Mutchler, Matt G; McDavitt, Bryce; Ghani, Mansur A; Nogg, Kelsey; Winder, Terrell J A; Soto, Juliana K

2015-09-01

Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

Risk Factors for Early and Late Transmission of HIV via Breast-Feeding among Infants Born to HIV-Infected Women in a Randomized Clinical Trial in Botswana

PubMed Central

Shapiro, Roger L.; Smeaton, Laura; Lockman, Shahin; Thior, lbou; Rossenkhan, Raabya; Wester, Carolyn; Stevens, Lisa; Moffat, Claire; Arimi, Peter; Ndase, Patrick; Asmelash, Aida; Leidner, Jean; Novitsky, Vladimir; Makhema, Joseph; Essex, Max

2009-01-01

Risk factors for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breast-feeding were evaluated in a randomized trial. HIV-infected women and their infants received zidovudine as well as single-dose nevirapine or placebo. Infants were randomized to formula-feed (FF) or breast-feed (BF) in combination with zidovudine prophylaxis. Of 1116 at-risk infants, 6 (1.1%) in the FF group and 7 (1.3%) in the BF group were infected between birth and 1 month)P = .99). Maternal receipt of nevirapine did not predict early MTCT in the BF group (P = .45). Of 547 infants in the BF group at risk for late MTCT, 24 (4.4%) were infected. Maternal HIV-1 RNA levels in plasma (P<.001) and breast milk (P<.001) predicted late MTCT. These findings support the safety of 1 month of breast-feeding in combination with maternal and infant antiretroviral prophylaxis. PMID:19090775

From subjects to relations: Bioethics and the articulation of postcolonial politics in the Cambodia Pre-Exposure Prophylaxis trial.

PubMed

Grant, Jenna M

2016-04-01

Controversies about global clinical trials, particularly HIV trials, tend to be framed in terms of ethics. In this article, I explore debates about ethics in the Cambodia Pre-Exposure Prophylaxis trial, which was designed to test the safety and efficacy of tenofovir as a prevention for HIV infection. Bringing together studies of public participation in science with studies of bioethics, I show how activists around the Cambodian Pre-Exposure Prophylaxis trial circulated and provoked debates about standards of research ethics, as opposed to research methodology. This postcolonial bioethics was configured through the circulation of and debate about ethics guidelines, and historically and culturally specific relations of vulnerability and responsibility between foreigners and Cambodians and between Cambodian leaders and Cambodian subjects. I argue that this shift in the object of ethical concern, from the experimental human subject to the relation between subjects and researchers, illustrates how a postcolonial field of articulation reformulates classical bioethics.

Galactomannan enzyme immunoassay and quantitative Real Time PCR as tools to evaluate the exposure and response in a rat model of aspergillosis after posaconazole prophylaxis.

PubMed

Cendejas-Bueno, Emilio; Forastiero, Agustina; Ruiz, Isabel; Mellado, Emilia; Buitrago, María José; Gavaldà, Joan; Gomez-Lopez, Alicia

2016-11-01

A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole. Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used. Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain. This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Late-onset Pneumocystis jirovecii pneumonia post-fludarabine, cyclophosphamide and rituximab: implications for prophylaxis.

PubMed

Haeusler, Gabrielle M; Slavin, Monica A; Seymour, John F; Lingaratnam, Senthil; Teh, Benjamin W; Tam, Constantine S; Thursky, Karin A; Worth, Leon J

2013-08-01

Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post-FCR in the era of highly sensitive molecular diagnostics and (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computerised tomography (CT). All patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory-confirmed PJP cases during this time were identified from an electronic database. Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, (18) F-FDG PET demonstrated bilateral ground-glass infiltrates. Median CD4(+) lymphocyte counts at time of PJP diagnosis and 9-12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4-24 months). Given the high rate of late-onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post-FCR, particularly in pretreated patients. Further evaluation of the role of CD4(+) monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors associated with coverage of cotrimoxazole prophylaxis in HIV-exposed children in South Africa.

PubMed

Moodley, Dhayendre; Reddy, Leanne; Mahungo, Wisani; Masha, Rebotile

2013-01-01

The World Health Organisation and the Joint United Nations Programme in 2006 reaffirmed the earlier recommendation of 2000 that all HIV-exposed infants in resource-poor countries should commence cotrimoxazole (CTX) prophylaxis at 6-weeks of life. CTX prophylaxis should be continued until the child is confirmed HIV-uninfected and there is no further exposure to breastmilk transmission. We determined CTX coverage and explored factors associated with CTX administration in HIV-exposed infants at a primary health clinic in South Africa. In a cross-sectional study of HIV-exposed infants 6-18 months of age attending a child immunisation clinic, data from the current visit and previous visits related to CTX prophylaxis, feeding practice and infant HIV testing were extracted from the child's immunisation record. Further information related to the administration of CTX prophylaxis was obtained from an interview with the child's mother. One-third (33.0%) HIV-exposed infants had not initiated CTX at all and breastfed infants were more likely to have commenced CTX prophylaxis as compared to their non-breastfed counterparts (78.7% vs 63.4%) (p = 0.008). Availability of infant's HIV status was strongly associated with continuation or discontinuation of CTX after 6 months of age or after breastfeeding cessation. Maternal self-reports indicated that only 52.5% (95%CI 47.5-57.5) understood the reason for CTX prophylaxis, 126 (47%) did not dose during weekends; 55 (21%) dosed their infants 3 times a day and 70 (26%) dosed their infants twice daily. A third of HIV-exposed children attending a primary health care facility in this South African setting did not receive CTX prophylaxis. Not commencing CTX prophylaxis was strongly associated with infants not breastfeeding and unnecessary continued exposure to CTX in this paediatric population was due to limited availability of early infant diagnosis. Attendance at immunization clinics can be seen as missed opportunities for early infant diagnosis of HIV and related care.

Factors Associated with Coverage of Cotrimoxazole Prophylaxis in HIV-Exposed Children in South Africa

PubMed Central

Moodley, Dhayendre; Reddy, Leanne; Mahungo, Wisani; Masha, Rebotile

2013-01-01

Background The World Health Organisation and the Joint United Nations Programme in 2006 reaffirmed the earlier recommendation of 2000 that all HIV-exposed infants in resource-poor countries should commence cotrimoxazole (CTX) prophylaxis at 6-weeks of life. CTX prophylaxis should be continued until the child is confirmed HIV-uninfected and there is no further exposure to breastmilk transmission. We determined CTX coverage and explored factors associated with CTX administration in HIV-exposed infants at a primary health clinic in South Africa. Methods In a cross-sectional study of HIV-exposed infants 6–18 months of age attending a child immunisation clinic, data from the current visit and previous visits related to CTX prophylaxis, feeding practice and infant HIV testing were extracted from the child's immunisation record. Further information related to the administration of CTX prophylaxis was obtained from an interview with the child's mother. Results One-third (33.0%) HIV-exposed infants had not initiated CTX at all and breastfed infants were more likely to have commenced CTX prophylaxis as compared to their non-breastfed counterparts (78.7% vs 63.4%) (p = 0.008). Availability of infant's HIV status was strongly associated with continuation or discontinuation of CTX after 6 months of age or after breastfeeding cessation. Maternal self-reports indicated that only 52.5% (95%CI 47.5–57.5) understood the reason for CTX prophylaxis, 126 (47%) did not dose during weekends; 55 (21%) dosed their infants 3 times a day and 70 (26%) dosed their infants twice daily. Conclusion A third of HIV-exposed children attending a primary health care facility in this South African setting did not receive CTX prophylaxis. Not commencing CTX prophylaxis was strongly associated with infants not breastfeeding and unnecessary continued exposure to CTX in this paediatric population was due to limited availability of early infant diagnosis. Attendance at immunization clinics can be seen as missed opportunities for early infant diagnosis of HIV and related care. PMID:23667599

Safe injection practice among health care workers, Gharbiya, Egypt.

PubMed

Ismail, Nanees A; Aboul Ftouh, Aisha M; El Shoubary, Waleed H

2005-01-01

A cross-sectional study was conducted in 25 health care facilities in Gharbiya governorate to assess safe injection practices among health care workers (HCWs). Two questionnaires, one to collect information about administrative issues related to safe injection and the other to collect data about giving injections, exposure to needle stick injuries, hepatitis B vaccination status and safe injection training. Practices of injections were observed using a standardized checklist. The study revealed that there was lack of both national and local infection control policies and lack of most of the supplies needed for safe injection practices. Many safe practices were infrequent as proper needle manipulation before disposal (41%), safe needle disposal (47.5%), reuse of used syringe & needle (13.2%) and safe syringe disposal (0%). Exposure to needle stick injuries were common among the interviewed HCWs (66.2%) and hand washing was the common post exposure prophylaxis measure (63.4%). Only 11.3% of HCWs had full course hepatitis B vaccination. Infection control -including safe injections- training programs should be afforded to all HCWs.

Human rabies in Tianjin, China.

PubMed

Montgomery, J P; Zhang, Y; Wells, E V; Liu, Y; Clayton, J L; Wang, X; Boulton, M L

2012-12-01

Human rabies has recently re-emerged as a significant public health threat in Tianjin, China. Using surveillance data compiled by the Tianjin Centers for Disease Control and Prevention, we describe 60 cases of human rabies reported from 2005 to 2011 in the municipality of Tianjin, China. All 60 cases of human rabies resulted in death. Cases were primarily male (80%), middle aged (mean 40.6 years), and exposed to rabies in a rural setting (82%). Most exposures were associated with dog bites (93%) and no animal had a history of rabies vaccination; no cases were laboratory confirmed. Fifteen percent of patients sought medical attention for their wound, and none received a complete regimen of WHO-recommended post-exposure prophylaxis (PEP). These findings suggest the need for China's public health authority to improve animal rabies surveillance and control strategies through laboratory case confirmation, more rapid response to potential exposures with provision of appropriate PEP, and education to the public and to health care providers on identifying and reducing rabies risk.

Kaposi's sarcoma: Good outcome with doxorubicin, bleomycin and vincristine sulphate (ABV) chemotherapy and highly active antiretroviral therapy.

PubMed

Hesseling, P B; Katayi, E; Wharin, P; Bardin, R; Kouya, F; Palmer, D; Glenn, M; Kruger, M

2017-10-31

There is little published information on effective treatment of Kaposi's sarcoma (KS) in children in low-income countries. We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with highly active antiretroviral therapy (HAART) plus co-trimoxazole prophylaxis for those who were HIV-positive, with additional vincristine if remission was not achieved after 4 months. Maintenance HAART plus co-trimoxazole was given to all HIV-positive patients. A fine-needle aspirate and CD4+ count were done if possible, and staging was performed according to Mitsuyasu. Eight of ten HIV-positive patients with stage III - IVB disease, and both HIV-negative patients with stage I disease, were in remission after 473 - 1 490 (mean 939) days. One patient died after absconding during treatment, and one died from neutropenia-related pulmonary infection. ABV with or without HAART is an effective treatment option for children with KS.

HIV-negative male couples' attitudes about pre-exposure prophylaxis (PrEP) and using PrEP with a sexual agreement.

PubMed

Mitchell, Jason W; Lee, Ji-Young; Woodyatt, Cory; Bauermeister, José; Sullivan, Patrick; Stephenson, Rob

2016-08-01

One efficacious strategy to help prevent HIV is oral pre-exposure prophylaxis (PrEP), a daily regimen of antiretroviral treatment taken by HIV-negative individuals. Two of the recommendations of Centers for Disease Control and Prevention (CDC) guidelines for PrEP pertain to being in a relationship (i.e., male couples). Despite the recognition of how primary partners in male couples' relationships shape HIV risk and CDC's PrEP guidelines, there is a paucity of data that examine HIV-negative male couples' attitudes toward PrEP use and using PrEP with a sexual agreement. A sexual agreement is an explicit agreement made between two individuals about what sex and other related behaviors may occur within and outside of their relationship. In this qualitative study, we examine HIV-negative male couples' attitudes toward PrEP use and whether they thought PrEP could be integrated into a sexual agreement. Data for this study are drawn from couple-level interviews conducted in 2014 with 29 HIV-negative male couples who had a sexual agreement and were from Atlanta or Detroit. Both passive (e.g., flyers) and active (e.g., targeted Facebook advertisements) recruitment methods were used; the sample was stratified by agreement type. Thematic analysis was applied to identify the following themes regarding HIV-negative male couples' attitudes toward PrEP use: (1) PrEP and condom use; (2) concerns about PrEP (e.g., effectiveness, side effects, and promoting sexually risky behavior); and (3) accessibility of PrEP. Some thought PrEP could be a part of couples' agreement because it could help reduce sexual anxiety and sexual risk, and would help keep the couple safe. Others described PrEP use with an agreement as something for "others". Some were also concerned that incorporating PrEP could usurp the need for a sexual agreement in a couples' relationship. These themes highlight the need to improve informational messaging and promotion efforts about PrEP among HIV-negative male couples who may benefit from using it.

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa

PubMed Central

Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R.; Bukusi, Elizabeth A.; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E.; Ware, Norma C.; Wyatt, Monique A.; Marzinke, Mark A.; Frenkel, Lisa M.; Celum, Connie; Baeten, Jared M.

2017-01-01

Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods: We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.   Conclusions: PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation. PMID:29355231

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa.

PubMed

Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R; Bukusi, Elizabeth A; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E; Ware, Norma C; Wyatt, Monique A; Marzinke, Mark A; Frenkel, Lisa M; Celum, Connie; Baeten, Jared M

2017-11-06

Introduction : Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods : We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results : We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.   Conclusions : PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.

Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation: A qualitative study.

PubMed

Bil, Janneke P; van der Veldt, Wendy M; Prins, Maria; Stolte, Ineke G; Davidovich, Udi

2016-09-01

Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM).Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach.Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients' medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support.To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling.

Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation

PubMed Central

Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi

2016-01-01

Abstract Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM). Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach. Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients’ medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support. To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling. PMID:27684827

On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

PubMed

Molina, Jean-Michel; Capitant, Catherine; Spire, Bruno; Pialoux, Gilles; Cotte, Laurent; Charreau, Isabelle; Tremblay, Cecile; Le Gall, Jean-Marie; Cua, Eric; Pasquet, Armelle; Raffi, François; Pintado, Claire; Chidiac, Christian; Chas, Julie; Charbonneau, Pierre; Delaugerre, Constance; Suzan-Monti, Marie; Loze, Benedicte; Fonsart, Julien; Peytavin, Gilles; Cheret, Antoine; Timsit, Julie; Girard, Gabriel; Lorente, Nicolas; Préau, Marie; Rooney, James F; Wainberg, Mark A; Thompson, David; Rozenbaum, Willy; Doré, Veronique; Marchand, Lucie; Simon, Marie-Christine; Etien, Nicolas; Aboulker, Jean-Pierre; Meyer, Laurence; Delfraissy, Jean-François

2015-12-03

Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge.

PubMed

Hobbs, Charlotte V; Anderson, Charles; Neal, Jillian; Sahu, Tejram; Conteh, Solomon; Voza, Tatiana; Langhorne, Jean; Borkowsky, William; Duffy, Patrick E

2017-01-01

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8 + T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The "AMA-Brazil" cooperative project: a nation-wide assessment of the clinical and epidemiological profile of AIDS-related deaths in Brazil in the antiretroviral treatment era.

PubMed

Veras, Maria Amelia de Sousa Mascena; Ribeiro, Manoel C A; Jamal, Leda Fátima; McFarland, Willi; Bastos, Francisco Inácio; Ribeiro, Karina Braga; Barata, Rita Barradas; Moraes, José Cassio de; Reingold, Arthur L

2011-01-01

The objective of this study was to assess the profile of AIDS-related deaths in the post antiretroviral therapy (ART) scale up period in Brazil. A case-control study was conducted including a nationally probabilistic sample of AIDS deaths and living controls. Data were abstracted from medical records and nation-wide databases of AIDS cases, mortality, ART care, and laboratory testing. Interrupted (adjusted odds ratio--AOR 4.35, 95%CI: 3.15-6.00) or no use of ART (AOR 2.39, 95%CI: 1.57-3.65) was the strongest predictor of death, followed by late diagnosis (AOR 3.95, 95%CI: 2.68-5.82). Criterion other than CD4 < 350 had a higher likelihood of death (AOR 1.65, 95%CI: 1.14-2.40). Not receiving recommended vaccines (AOR, 1.76, 95%CI: 1.21-2.56), presenting AIDS-related diseases (AOR 2.19, 95%CI: 1.22-3.93) and tuberculosis (AOR 1.50, 95%CI: 1.14-1.97) had higher odds of death. Being an injecting drug user (IDU) had a borderline association with higher odds of death, while homo/bisexual exposure showed a protective effect. Despite remarkable successes, Brazilians continue to die of AIDS in the post-ART scale up period. Many factors contributing to continued mortality are preventable.

Assessment of Quality of Life in a Cohort of Newly Diagnosed Patients on HAART Regimen, in Resource Restricted Tribal Region of Chhattisgarh, India: A Prospective Study

PubMed Central

Singh, Harminder; Kaur, Kamalpreet; Dulhani, Navin; Bansal, Akash; Kumar, Bithika N.; Chouhan, Vinod Kumar Singh

2013-01-01

Background: Highly active antiretroviral therapy regimens have resulted in the systemic/clinical healing for human immune deficiency virus-infected patients but the consequence of antiretroviral therapy on the whole quality of life has become a major concern. The current study correlates the relationship of quality of life with successful highly active antiretroviral therapy. Aim: To determine the health-related quality of life in human immune deficiency virus-infected patients on highly active anti-retroviral therapy regimen in tribal region of Chhattisgarh. Design: An open label prospective study. Materials and Methods: Health-related quality of life was assessed using a standardized questionnaire, the Medical Outcomes Survey Short Form 36. Physical health summary scores and mental health summary scores were compared of pre-Highly Active Anti-Retroviral Therapy (at baseline) and post 12 months of therapy. Results: The increase in CD4 cell counts was extremely significant (P < 0.0001). The Physical Composite Summary (P value = 0.0003) improved significantly, whereas the Mental Composite Summary (with a baseline value of 40.7), post 12 months, was calculated as 42.8 (P value = 0.2371) and was statistically not significant. Conclusion: Efficacy measurement is the key ingredient of highly active anti-retroviral therapy, which must also include assessment of health-related quality of life to maximize the holistic approach towards disease. PMID:24049364

[Healthcare profile of rabies pre-exposure prophylaxis in the state of Rio Grande do Sul, Brazil, 2007-2014].

PubMed

Mota, Roberta Silva Silveira da; Schuch, Luiz Filipe Damé; Schuch, Dóris Gómez Marcos; Osmari, Christieli Prestes; Guimarães, Tássia Gomes

2016-01-01

to describe the profile of healthcare provision regarding rabies pre-exposure prophylaxis (RPrEP) in the state of Rio Grande do Sul, Brazil, as compared with the Technical Standards for Rabies Prophylaxis in Humans. this was a descriptive study using Notifiable Disease Information System data on anti-rabies healthcare provided between 2007 and 2014. only 2.4% of anti-rabies healthcare related to RPrEP (5,721/239,245), 42.5% of these were veterinary, biology and zootechnics students and 10.3% were professionals from the same areas; individuals aged 20 to 64 accounted for 71.8% of the total number of people vaccinated and the frequency of this form of prophylaxis was 53.5/100,000 inhabitants for the state as a whole, varying between 13.1 to 185.1/100,000 inhabitants in the state's different health districts. RPrEP frequency was found to be low, suggesting that this rabies prevention tool has been neglected, leaving a large number of people at occupational risk.

Same dog bite and different outcome in two cases - case report.

PubMed

Rd, Gadekar; Vk, Domple; If, Inamdar; Nr, Aswar; Mk, Doibale

2014-06-01

There is still no cure for rabies and survival from clinical rabies is extremely rare. It is a preventable disease if the post exposure prophylaxis is initiated in time and administered as per WHO guidelines including administration of rabies immunoglobulin. The role of passive rabies immunization products is to provide the immediate availability of neutralizing antibodies at the site of the exposure before it is physiologically possible for the patient to begin producing his or her own antibodies after vaccination. In this case report, the same dog has bitten to a boy and to an adult. Local wound treatment and use of human rabies immunoglobulin as well as gluteal region as a site of bite were the probable reasons for survival of the boy. On the other hand no local wound treatment, no use of rabies immunoglobulin and finger as a site of bite are the probable reasons for death of an adult due to rabies.

Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics

PubMed Central

Noecker, Cecilia; Schaefer, Krista; Zaccheo, Kelly; Yang, Yiding; Day, Judy; Ganusov, Vitaly V.

2015-01-01

Upon infection of a new host, human immunodeficiency virus (HIV) replicates in the mucosal tissues and is generally undetectable in circulation for 1–2 weeks post-infection. Several interventions against HIV including vaccines and antiretroviral prophylaxis target virus replication at this earliest stage of infection. Mathematical models have been used to understand how HIV spreads from mucosal tissues systemically and what impact vaccination and/or antiretroviral prophylaxis has on viral eradication. Because predictions of such models have been rarely compared to experimental data, it remains unclear which processes included in these models are critical for predicting early HIV dynamics. Here we modified the “standard” mathematical model of HIV infection to include two populations of infected cells: cells that are actively producing the virus and cells that are transitioning into virus production mode. We evaluated the effects of several poorly known parameters on infection outcomes in this model and compared model predictions to experimental data on infection of non-human primates with variable doses of simian immunodifficiency virus (SIV). First, we found that the mode of virus production by infected cells (budding vs. bursting) has a minimal impact on the early virus dynamics for a wide range of model parameters, as long as the parameters are constrained to provide the observed rate of SIV load increase in the blood of infected animals. Interestingly and in contrast with previous results, we found that the bursting mode of virus production generally results in a higher probability of viral extinction than the budding mode of virus production. Second, this mathematical model was not able to accurately describe the change in experimentally determined probability of host infection with increasing viral doses. Third and finally, the model was also unable to accurately explain the decline in the time to virus detection with increasing viral dose. These results suggest that, in order to appropriately model early HIV/SIV dynamics, additional factors must be considered in the model development. These may include variability in monkey susceptibility to infection, within-host competition between different viruses for target cells at the initial site of virus replication in the mucosa, innate immune response, and possibly the inclusion of several different tissue compartments. The sobering news is that while an increase in model complexity is needed to explain the available experimental data, testing and rejection of more complex models may require more quantitative data than is currently available. PMID:25781919

18-Month Effectiveness of Short-Course Antiretroviral Regimens Combined with Alternatives to Breastfeeding to Prevent HIV Mother-to-Child Transmission

PubMed Central

Leroy, Valériane; Ekouevi, Didier K.; Becquet, Renaud; Viho, Ida; Dequae-Merchadou, Laurence; Tonwe-Gold, Besigin; Rouet, François; Sakarovitch, Charlotte; Horo, Appolinaire; Timité-Konan, Marguerite; Rouzioux, Christine; Dabis, François

2008-01-01

Objective We assessed the 18-month effectiveness of short-course (sc) antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT) of HIV-1 in Abidjan, Côte d'Ivoire. Methodology HIV-1 infected pregnant women received from ≥32–36 weeks of gestation scZidovudine (ZDV)+/−Lamivudine (3TC)+single-dose Nevirapine (sdNVP) at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001–2003). Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994–2000) exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged ≥18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR) and effectiveness (HIV-free survival) were compared by exposure group using a Cox model. Findings Among 926 live-born children enrolled, 107 (11.6%) were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16–30%) in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10–27%) in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6–14%) in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4–11%) in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2–10%) in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20–70%) for ZDV+sdNVP formula fed children to 63% (CI:40–80%) for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART), home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa, even in short-term breastfed children. The two sc antiretroviral combinations associated to any of the two infant feeding interventions, formula-feeding and shortened breastfeeding, reduce significantly MTCT with long-term benefit until age 18 months and without increasing mortality. PMID:18286200

TSPY4 is a novel sperm-specific biomarker of semen exposure in human cervicovaginal fluids; potential use in HIV prevention and contraception studies.

PubMed

Jacot, Terry A; Zalenskaya, Irina; Mauck, Christine; Archer, David F; Doncel, Gustavo F

2013-09-01

Developing an objective, reliable method to determine semen exposure in cervicovaginal fluids is important for accurately studying the efficacy of vaginal microbicides and contraceptives. Y-chromosome biomarkers offer better stability, sensitivity, and specificity than protein biomarkers. TSPY4 belongs to the TSPY (testis-specific protein Y-encoded) family of homologous genes on the Y-chromosome. Using a multiplex PCR amplifying TSPY4, amelogenin, and Sex-determining region in the Y chromosome (SRY), our objective was to determine whether a gene in the TSPY family was a more sensitive marker of semen exposure in cervicovaginal fluids than SRY. The multiplex polymerase chain reaction (PCR) was developed using sperm and vaginal epithelial (female) DNA. Diluted sperm DNA and mixed male/female DNA was used to determine the sensitivity of the multiplex PCR. Potential interference of TSPY4 amplification by components in cervicovaginal and seminal fluids was determined. TSPY4 and SRY amplification was also investigated in women participating in a separate IRB-approved clinical study in which cervicovaginal swab DNA was collected before semen exposure and at various time points after exposure. TSPY4, SRY, and amelogenin were amplified in sperm DNA, but only amelogenin in female DNA. The limit of sperm DNA from which TSPY4 could be amplified was lower than SRY (4 pg vs 80 pg). TSPY4 could also be amplified from mixed male/female DNA. Amplification was not affected by cervicovaginal and seminal components. Using cervicovaginal swab DNA from three women before and after semen exposure, TSPY4 was detected up to 72 h post exposure while SRY detection was observed up to 24-48 h. TSPY4 was detected up to 7 days post exposure in one out of three women. We have demonstrated that TSPY4 is a new sensitive, and sperm-specific biomarker. The multiplex PCR incorporating this new biomarker has potential to be an objective measure for determining semen exposure in clinical trials of vaginal products such as contraceptives and HIV pre/post-exposure prophylaxis agents. Copyright © 2013 Elsevier Inc. All rights reserved.

Cumulative Exposure to Cell-Free HIV in Breast Milk, Rather Than Feeding Pattern per se, Identifies Postnatally Infected Infants

PubMed Central

Neveu, Dorine; Viljoen, Johannes; Bland, Ruth M.; Nagot, Nicolas; Danaviah, Siva; Coutsoudis, Anna; Rollins, Nigel Campbell; Coovadia, Hoosen M.; Van de Perre, Philippe; Newell, Marie-Louise

2011-01-01

Background. We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure. Methods. Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern. Results. Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ∼15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 106 copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001). Conclusions. Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants. PMID:21367736

Randomised controlled trial of prophylactic antibiotic treatment for the prevention of endophthalmitis after open globe injury at Groote Schuur Hospital.

PubMed

Du Toit, N; Mustak, S; Cook, C

2017-07-01

Most post-traumatic acute infectious endophthalmitis occur within a week of open globe trauma, necessitating early antibiotic prophylaxis. There are few randomised studies that demonstrate the benefits of prophylactic antibiotics. This randomised controlled non-inferiority trial was aimed at determining the incidence of post-traumatic endophthalmitis using established intravenous/oral prophylaxis and comparing this to the incidence using oral antibiotics only. All adult patients admitted with open globe injury were included. Those with proven endophthalmitis, high-risk features, who underwent primary evisceration and those allergic to the trial antibiotics were excluded. Patients were randomised to receive either intravenous cefazolin and oral ciprofloxacin or oral ciprofloxacin and oral cefuroxime for 3 days from admission. Acute endophthalmitis was the primary outcome. Patients completed the study if they were followed up for 6 weeks post injury. Three hundred patients were enrolled, with 150 in each arm. There were 99 exclusions. Seven patients developed endophthalmitis despite prophylaxis-2.0% (three cases) in the intravenous and oral arm, compared with 2.7% (four cases) in the oral-only arm-this difference was not statistically significant ( p=0.703). The incidence of endophthalmitis with prophylaxis was 2-3%. Selected patients with open globe injuries (without high-risk features) may receive either intravenous cefazolin and oral ciprofloxacin, or oral cefuroxime and oral ciprofloxacin as prophylaxis against acute endophthalmitis-the latter regimen has the advantage of shortening patients' hospital stays and reducing costs. Non-inferiority study-design limitations should be taken into account, however. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Surveillance and control of rabies in La Reunion, Mayotte, and Madagascar

PubMed Central

2013-01-01

Mayotte and La Reunion islands are currently free of animal rabies and surveillance is performed by the French Human and Veterinary Public Health Services. However, dog rabies is still enzootic in Madagascar with 4 to 10 confirmed human cases each year. The number of antirabies medical centres in Madagascar is still scarce to provide easy access to the local population for post-exposure rabies prophylaxis. Furthermore, stray dog populations are considerable and attempts to control rabies by mass campaigns of dog vaccination have not received sufficient attention from the national health authorities. To address these challenges, an expanded program to control rabies needs to be initiated by the Malagasy authorities. PMID:24016204

Imported episodic rabies increases patient demand for and physician delivery of antirabies prophylaxis.

PubMed

Lardon, Zélie; Watier, Laurence; Brunet, Audrey; Bernède, Claire; Goudal, Maryvonne; Dacheux, Laurent; Rotivel, Yolande; Guillemot, Didier; Bourhy, Hervé

2010-06-22

Imported cases threaten rabies reemergence in rabies-free areas. During 2000-2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). Annual data collected by the National Reference Center for Rabies NRCR (1989-2006) and the exhaustive database (2000-2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000-2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy.

Imported Episodic Rabies Increases Patient Demand for and Physician Delivery of Antirabies Prophylaxis

PubMed Central

Lardon, Zélie; Watier, Laurence; Brunet, Audrey; Bernède, Claire; Goudal, Maryvonne; Dacheux, Laurent; Rotivel, Yolande

2010-01-01

Background Imported cases threaten rabies reemergence in rabies-free areas. During 2000–2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). Methodology/Principal Findings Annual data collected by the National Reference Center for Rabies NRCR (1989–2006) and the exhaustive database (2000–2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000–2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. Conclusions Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy. PMID:20582307

Geographical and temporal patterns of rabies post exposure prophylaxis (PEP) incidence in humans in the Mekong River Delta and Southeast Central Coast regions in Vietnam from 2005 to 2015

PubMed Central

Thiem, Vu Dinh; Anh, Dang Duc; Duong, Tran Nhu; Lee, Mihye; Grace, Delia; Nguyen-Viet, Hung

2018-01-01

Background In Vietnam, rabies has been a notifiable disease for more than 40 years. Over the last five years, on average, more than 350,000 people per year have been bitten by dogs and cats while more than 80 human deaths have been reported yearly. No studies have been conducted to evaluate the geographical and temporal patterns of rabies in humans in Vietnam. Therefore, the main objective of this study was to assess the geographical and temporal distributions of rabies post exposure prophylaxis (PEP) incidence in humans in Vietnam from 2005 to 2015. Methods Average incidence rabies (AIR) PEP rates for every 3 or 4 years (2005–2008, 2009–2012 and 2013–2015) were calculated to describe the spatial distribution of rabies PEP. Hotspot analysis was implemented to identify patterns of spatial significance using the Getis-Ord Gi statistic. For temporal pattern analysis, two regions [Mekong River Delta (MRD) and Southeast Central Coast (SCC)], with the highest incidence rates, and the seasonal-decomposition procedure based on loess (STL), were compared to assess their temporal patterns of rabies PEP. Findings We found hotspots in southern Vietnam and coldspots in northern Vietnam during the study period. Rabies cases were limited to specific areas. In addition, the hotspot analysis showed that new risk areas were identified in each period which were not observed in incidence rate maps. The seasonal plots showed seasonal patterns with a strong peak in February/July and a minor peak in October/December in the MRD region. However, in the SCC, a small peak was detected at the early part of each year and a strong peak in the middle of each year. Conclusion Our findings provide insight into understanding the geographical and seasonal patterns of rabies PEP in Vietnam. This study provides evidence to aid policy makers when making decisions and investing resources. Such information may also be utilized to raise public awareness to prevent rabies exposures and reduce unnecessary PEP. PMID:29634746

Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review.

PubMed

Devleesschauwer, Brecht; Aryal, Arjun; Sharma, Barun Kumar; Ale, Anita; Declercq, Anne; Depraz, Stephanie; Gaire, Tara Nath; Gongal, Gyanendra; Karki, Surendra; Pandey, Basu Dev; Pun, Sher Bahadur; Duchateau, Luc; Dorny, Pierre; Speybroeck, Niko

2016-02-01

Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10-100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle. Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal.

Birth defects among a cohort of infants born to HIV-infected women on antiretroviral medication

PubMed Central

Watts, D. Heather; Huang, Sharon; Culnane, Mary; Kaiser, Kathleen A.; Scheuerle, Angela; Mofenson, Lynne; Stanley, Kenneth; Newell, Marie-Louise; Mandelbrot, Laurent; Delfraissy, Jean-Francois; Cunningham, Coleen K.

2011-01-01

Objective To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy. Methods Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry. Results Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3–5.4%) infants including 30/636 (4.7%; 95% CI 3.2–6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6–5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4–4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3–1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted. Conclusion ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance. PMID:21142844

Exposure ethics: does HIV pre-exposure prophylaxis raise ethical problems for the health care provider and policy maker?

PubMed

Venter, Francois; Allais, Lucy; Richter, Marlise

2014-07-01

The last few years have seen dramatic progress in the development of HIV pre-exposure prophylaxis (PrEP). These developments have been met by ethical concerns. HIV interventions are often thought to be ethically difficult. In a context which includes disagreements over human rights, controversies over testing policies, and questions about sexual morality and individual responsibility, PrEP has been seen as an ethically complex intervention. We argue that this is mistaken, and that in fact, PrEP does not raise new ethical concerns. Some of the questions posed by PrEP are not specific to HIV prophylaxis, but simply standard public health considerations about resource allocation and striking a balance between individual benefit and public good. We consider sexual disinhibition in the context of private prescriptions, and conclude that only unjustified AIDS-exceptionalism or inappropriate moralism about sex supports thinking that PrEP raises new ethical problems. This negative conclusion is significant in a context where supposed ethical concerns about PrEP have been raised, and in the context of HIV exceptionalism. © 2013 John Wiley & Sons Ltd.

Acceptability of pre-exposure prophylaxis as an HIV prevention strategy: barriers and facilitators to pre-exposure prophylaxis uptake among at-risk Peruvian populations.

PubMed

Galea, J T; Kinsler, J J; Salazar, X; Lee, S-J; Giron, M; Sayles, J N; Cáceres, C; Cunningham, W E

2011-05-01

This study examined pre-exposure prophylaxis (PrEP) acceptability among female sex workers, male-to-female transgendered persons and men who have sex with men in Lima, Peru. Focus groups explored social issues associated with PrEP acceptability and conjoint analysis assessed preferences among eight hypothetical PrEP scenarios with varying attribute profiles and their relative impact on acceptability. Conjoint analysis revealed that PrEP acceptability ranged from 19.8 to 82.5 out of a possible score of 100 across the eight hypothetical PrEP scenarios. Out-of-pocket cost had the greatest impact on PrEP acceptability (25.2, P < 0.001), followed by efficacy (21.4, P < 0.001) and potential side-effects (14.7, P < 0.001). Focus group data supported these findings, and also revealed that potential sexual risk disinhibition, stigma and discrimination associated with PrEP use, and mistrust of health-care professionals were also concerns. These issues will require careful attention when planning for PrEP roll-out.

Sex, PrEP, and Stigma: Experiences with HIV Pre-exposure Prophylaxis Among New York City MSM Participating in the HPTN 067/ADAPT Study.

PubMed

Franks, Julie; Hirsch-Moverman, Yael; Loquere, Avelino S; Amico, K Rivet; Grant, Robert M; Dye, Bonnie J; Rivera, Yan; Gamboa, Robert; Mannheimer, Sharon B

2018-04-01

The HPTN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study evaluated daily and non-daily dosing schedules for oral pre-exposure prophylaxis (PrEP) to prevent HIV. A qualitative sub-study including focus groups and in-depth interviews was conducted among men who have sex with men participating in New York City to understand their experience with PrEP and study dosing schedules. The 37 sub-study participants were 68% black, 11% white, and 8% Asian; 27% were of Hispanic/Latino ethnicity. Mean age was 34 years. Themes resulting from qualitative analysis include: PrEP is a significant advance for HIV prevention; non-daily dosing of PrEP is congruent with HIV risk; and pervasive stigma connected to HIV and risk behavior is a barrier to PrEP adherence, especially for non-daily dosing schedules. The findings underscore how PrEP intersects with other HIV prevention practices and highlight the need to understand and address multidimensional stigma related to PrEP use.

The costs and benefits of private sector provision of treatment to HIV-infected employees in Kampala, Uganda.

PubMed

Marseille, Elliot; Saba, Joseph; Muyingo, Sowedi; Kahn, James G

2006-04-04

The objective of this study was to determine the financial incentives that companies have to treat HIV-infected employees, in a health care services company in Kampala, Uganda. Cost-benefit analysis from the company's perspective of three interventions to treat HIV-infected employees. The costs and benefits of each intervention were compared with no intervention and with each other: cotrimoxazole prophylaxis (CTX) starting at WHO stage 2; highly active antiretroviral therapy (HAART) plus CTX starting at WHO stage 2; and a 'hybrid' strategy that begins with CTX at WHO stage 2 and later includes HAART. The 5-year health and economic outcomes were calculated using a Markov model. Inputs for disease progression rates and effects of HIV on company costs were derived from published and unpublished data and a survey administered to company officers. The analysis showed that the 'hybrid' intervention is the most cost-effective. For 100 skilled employees it would save the company 38,939 US dollars and 73 disability adjusted life-years (DALYs). For unskilled workers 'CTX' is the most cost effective and would save 16,417 US dollars and 60 DALYs. 'Hybrid' has an incremental cost-effectiveness ratio of 45 US dollars per DALY for unskilled workers whereas HAART is far less economical at an incremental cost per DALY of 4118 US dollars. For 'CTX', net savings are preserved across the full range of input values. A 'hybrid' intervention combining CTX prophylaxis followed by HAART would generate savings to a Ugandan company. Governments and other donors may find opportunities to share costs with the private sector as part of their phase-in strategy for antiretroviral therapy.

Improving outcomes in infants of HIV-infected women in a developing country setting.

PubMed

Noel, Francine; Mehta, Sapna; Zhu, Yuwei; Rouzier, Patricia De Matteis; Marcelin, Abdias; Shi, Jian R; Nolte, Claudine; Severe, Linda; Deschamps, Marie Marcelle; Fitzgerald, Daniel W; Johnson, Warren D; Wright, Peter F; Pape, Jean W

2008-01-01

Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries. We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis. Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.

Impact of Maternal and Infant Antiretroviral Drug Regimens on Drug Resistance in HIV-Infected Breastfeeding Infants

PubMed Central

Fogel, Jessica M.; Mwatha, Anthony; Richardson, Paul; Brown, Elizabeth R.; Chipato, Tsungai; Alexandre, Michel; Moodley, Dhayendre; Elbireer, Ali; Mirochnick, Mark; George, Kathleen; Mofenson, Lynne M.; Zwerski, Sheryl; Coovadia, Hoosen M.; Eshleman, Susan H.

2013-01-01

BACKGROUND The HPTN 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV-infection despite prophylaxis. METHODS HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher’s exact tests were used to evaluate associations between categorical variables. RESULTS NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in seven (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8=75% in the NVP arm, 1/17=5.9% in the placebo arm, P=0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral (ARV) treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all four of those infants by 6 months of age (4/4=100%). In contrast, only three (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate ARV treatment developed NVP resistance (P=0.003). CONCLUSIONS Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants. PMID:23249916

Provider Attitudes Toward Oral Preexposure Prophylaxis for HIV Prevention Among High-Risk Men Who Have Sex with Men in Lima, Peru

PubMed Central

Tang, Eric C.; Sobieszczyk, Magdalena E.; Shu, Eileen; Gonzales, Pedro; Sanchez, Jorge

2014-01-01

Abstract Oral preexposure prophylaxis (PrEP) was the first biomedical intervention to demonstrate efficacy in preventing HIV infection among men who have sex with men (MSM). Healthcare providers' attitudes toward PrEP will be critical in translating this finding into effective public health rollout programs. In a convenience sample of 186 healthcare providers in Peru, we assessed knowledge, barriers, and attitudes to prescribe and monitor HIV PrEP for high-risk MSM and transgender women, the populations with the highest HIV incidence in this setting. A total of 57.5% reported awareness of PrEP, and awareness was independently associated with caring for more than 50 MSM (OR: 3.67, p<0.002). Lack of local guidelines, concern about increased high-risk behavior, antiretroviral drug resistance, and limited availability of antiretrovirals for HIV-infected individuals were the most common barriers to prescribing PrEP. Of all physicians 44.6% indicated that they would be likely to prescribe oral PrEP now; likelihood to prescribe was higher if PrEP were supported by local guidelines (70.3%, p<0.001), if more trials supported its effectiveness (68.5%, p<0.001), and if intermittent use were shown to be effective (62.2%, p=0.019). Physicians were more likely to prescribe PrEP now if they care for more than 50 MSM (OR: 6.62, p=0.010). Infectious disease specialists were less likely to prescribe PrEP (OR: 0.10, p=0.003) than nonspecialists. Successful large-scale implementation of PrEP in Peru will require focused educational campaigns to increase awareness and address concerns among healthcare providers. PMID:24319983

[Prevention of HIV vertical transmission: obstetricians' attitude in Salvador, Brazil].

PubMed

Farias, João Paulo Queiroz; Franco, Anamélia; Santos, Kleber Pimentel; Dourado, Inês; Galvão-Castro, Bernardo

2008-03-01

to evaluate the attitudes and knowledge of obstetricians from public maternities in Salvador city (PMS) about the recommendations from the Health Ministry (HM) for the prophylaxis of vertical transmission of HIV (VTH) and antiretroviral therapy in pregnant women. The influence of working conditions, availability for quick testing and antiretroviral therapy has also been evaluated concerning the application of these recommendations. a transversal study from August to November 2005, involving 129/152 (85%) of the obstetricians from all the PMS. The instrument used was a structured and self-explanatory anonymous questionnaire, with questions on the population characteristics, working conditions and availability of material, knowledge and attitudes related to HIV counseling and testing, and proceedings with the patients (use of AZT, recognition of risk factors, choice and management of type of delivery and puerperal care). 69% of the obstetricians stated they knew integrally the HM recommendations, 90.7% agreed with the compulsory request of quick testing for HIV; 63.6% chose the caesarean section as the type of delivery; 38% were against normal delivery; 37.5% recommended isolation of positive serum patients and 58.1% indicated tubal ligation. Most of them (90%) mentioned the existence of factors unfavorable to the recommendations applicability, and among those factors, the most pointed were the inadequate way the pre-natal admission was done and the lack of information at that occasion. Even though the quick testing was available, only one third of the interviewees stated that the result was always available in due time. some attitudes related to the assistance to the pregnant women with HIV were incompatible with the HM recommendations. According to the interviewees, the inadequacy of the pre-natal plus the non-availability of quick testing, influence negatively the applicability of VTH prophylaxis recommendations.

Provider attitudes toward oral preexposure prophylaxis for HIV prevention among high-risk men who have sex with men in Lima, Peru.

PubMed

Tang, Eric C; Sobieszczyk, Magdalena E; Shu, Eileen; Gonzales, Pedro; Sanchez, Jorge; Lama, Javier R

2014-05-01

Oral preexposure prophylaxis (PrEP) was the first biomedical intervention to demonstrate efficacy in preventing HIV infection among men who have sex with men (MSM). Healthcare providers' attitudes toward PrEP will be critical in translating this finding into effective public health rollout programs. In a convenience sample of 186 healthcare providers in Peru, we assessed knowledge, barriers, and attitudes to prescribe and monitor HIV PrEP for high-risk MSM and transgender women, the populations with the highest HIV incidence in this setting. A total of 57.5% reported awareness of PrEP, and awareness was independently associated with caring for more than 50 MSM (OR: 3.67, p<0.002). Lack of local guidelines, concern about increased high-risk behavior, antiretroviral drug resistance, and limited availability of antiretrovirals for HIV-infected individuals were the most common barriers to prescribing PrEP. Of all physicians 44.6% indicated that they would be likely to prescribe oral PrEP now; likelihood to prescribe was higher if PrEP were supported by local guidelines (70.3%, p<0.001), if more trials supported its effectiveness (68.5%, p<0.001), and if intermittent use were shown to be effective (62.2%, p=0.019). Physicians were more likely to prescribe PrEP now if they care for more than 50 MSM (OR: 6.62, p=0.010). Infectious disease specialists were less likely to prescribe PrEP (OR: 0.10, p=0.003) than nonspecialists. Successful large-scale implementation of PrEP in Peru will require focused educational campaigns to increase awareness and address concerns among healthcare providers.

Survey of Intraocular Antibiotics Prophylaxis Practice after Open Globe Injury in China.

PubMed

Lou, Bingsheng; Lin, Lixia; Tan, Junlian; Yang, Yao; Yuan, Zhaohui; Lin, Xiaofeng

2016-01-01

To elucidate the Chinese practice of intraocular antibiotics administration for prophylaxis after open globe injury. A cross-sectional questionnaire survey was performed online by scanning a Quickmark (QR) code with smartphones at the 20th Chinese National Conference of Ocular Trauma in November 2014. A total of 153 (30.6%) of all participators at the conference responded. Of the respondents, 20.9% were routinely administered with prophylactic intraocular injection of antibiotics at the conclusion of the primary eye repair, and 56.9% were used only in cases with high risk of endophthalmitis development. The intraocular route of delivery was mainly included with intracameral injection (47.9%) and intravitreal injection (42.0%). Cephalosporins (53.8%) and vancomycin (42.0%) were the main choices of antibiotic agents, followed by fluoroquinolones (24.3%), and aminoglycosides (13.4%). Only 21.9% preferred a combination of two or more two drugs routinely. In addition, significantly more respondents from the referral eye hospital (92.7%) replied using intraocular antibiotics injection for prophylaxis compared to those respondents from the primary hospital (69.4%) (p = 0.001, Fisher's exact test). Intraocular antibiotics injection for post-traumatic endophthalmitis prophylaxis is widely used in China. However, the choice of antibiotic agents and the intraocular route of delivery vary. A well-designed clinical trial is needed to establish a standardized protocol of intraocular antibiotics administration for post-traumatic endophthalmitis prophylaxis.

Chemoprophylaxis for HIV prevention: new opportunities and new questions.

PubMed

Mayer, Kenneth H; Venkatesh, Kartik K

2010-12-01

Growing data suggest that antiretrovirals can be used as an effective means of HIV prevention. This article reviews the current status and future clinical prospects of utilizing antiretroviral chemoprophylaxis before and after high-risk HIV exposure to prevent HIV transmission. The discussion about using antiretrovirals as a means of primary HIV prevention has moved to the forefront of public health discourse because of a growing evidence base, the increased tolerability of the medications, the decreased cost, the ever-expanding formulary, and the limitations of other approaches.