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Sample records for combination antiretroviral treatment

  1. Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults

    PubMed Central

    Achenbach, Chad J; Darin, Kristin M; Murphy, Robert L; Katlama, Christine

    2011-01-01

    In the past 15 years, improvements in the management of HIV infection have dramatically reduced morbidity and mortality. Similarly, rapid advances in antiretroviral medications have resulted in the possibility of life-long therapy with simple and tolerable regimens. Protease inhibitors have been important medications in regimens of combination antiretroviral therapy for the treatment of HIV. One of the recommended and commonly used therapies in this class is once-daily-administered atazanavir, pharmacologically boosted with ritonavir (atazanavir/r). Clinical studies and practice have shown these drugs, in combination with other antiretroviral agents, to be potent, safe and easy to use in a variety of settings. Atazanavir/r has minimal short-term toxicity, including benign bilirubin elevation, and has less potential for long-term complications of hyperlipidemia and insulin resistance compared with other protease inhibitors. A high genetic barrier to resistance and a favorable resistance profile make it an excellent option for initial HIV treatment or as the first drug utilized in the protease inhibitors class. Atazanavir/r is also currently being studied in novel treatment strategies, including combinations with new classes of antiretrovirals to assess nucleoside reverse transcriptase inhibitor-sparing regimens. In this article we review atazanavir/r as a treatment for HIV infection and discuss the latest information on its pharmacology, efficacy and toxicity. PMID:21731578

  2. Pubertal Onset in HIV-infected Children in the Era of Combination Antiretroviral Treatment

    PubMed Central

    WILLIAMS, Paige L.; ABZUG, Mark J.; JACOBSON, Denise L.; WANG, Jiajia; VAN DYKE, Russell B.; HAZRA, Rohan; PATEL, Kunjal; DIMEGLIO, Linda A.; MCFARLAND, Elizabeth J.; SILIO, Margarita; BORKOWSKY, William; SEAGE, George R.; OLESKE, James M.; GEFFNER, Mitchell E.

    2014-01-01

    Objective To evaluate associations of perinatal HIV infection (PHIV), HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Design Analysis of data from two U.S. longitudinal cohort studies [IMPAACT 219C and PHACS AMP], conducted 2000–2012, including PHIV and HIV-exposed uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. Methods We compared the timing of pubertal onset (Tanner stage ≥2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. Results The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to 453 HEU children (10.3 vs 9.6, 10.5 vs 10.0, 11.3 vs 10.4, and 11.5 vs 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all p<0.001). PHIV youth with HIV-1 RNA viral load >10,000 copies/mL (vs ≤10,000 copies/mL) or CD4% <15% (vs ≥15%) had significantly later pubertal onset (by 4–13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6- to1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Conclusions Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset. PMID:24145244

  3. Lung cancer in HIV-infected patients in the combination antiretroviral treatment era

    PubMed Central

    Moltó, José; Sirera, Guillem; Clotet, Bonaventura

    2015-01-01

    The advent of combination antiretroviral treatment (cART) has been followed by a decrease in HIV-associated morbidity and mortality, but also by an apparent increase in the incidence of non-AIDS-defining cancers (NADCs). The risk of lung cancer is substantially higher in HIV-infected patients than in the general population, in part due to aging and tobacco use, and it is the most frequent NADC. The management of lung cancer in HIV-infected patients has some peculiarities that need to be taken into account. This review focuses on the epidemiology, risk factors, and clinical management of lung cancer in HIV-infected patients. In addition, screening tools and future perspectives are also discussed. Keywords Lung cancer; non-AIDS-defining cancers (NADCs); HIV infection; antiretroviral treatment PMID:26798577

  4. Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

    PubMed Central

    Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

    2016-01-01

    Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

  5. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment

    PubMed Central

    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D.; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-01-01

    Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+ cell count increase following its reinitiation in chronic infection (CHI). Design: Longitudinal observational study. Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as ‘pretreated in EHI’ if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4+ cell count (∼80 cells/μl; P < 0.001) and retained significantly higher CD4+ cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4+ cell count, differences in CD4+ cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Conclusion: Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI. PMID:26636925

  6. Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy

    PubMed Central

    Sadiq, Shamiya; Khajuria, Vijay; Mahajan, Annil; Singh, Jang B.

    2015-01-01

    Background and Objectives Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). Materials and Methods A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. Results Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. Conclusion The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field. PMID:26557538

  7. Comparison of efavirenz and protease inhibitor based combination antiretroviral therapy regimens in treatment-naïve people living with HIV with baseline resistance.

    PubMed

    Lim, Charlotte; McFaul, Katie; Kabagambe, Samuel; Sonecha, Sonali; Jones, Rachael; Asboe, David; Pozniak, Anton; Nwokolo, Nneka; Boffito, Marta

    2016-07-17

    A retrospective cohort analysis comparing the efficacy of boosted protease inhibitor-based and efavirenz-based combination antiretroviral therapy in treatment-naïve people living with HIV with baseline resistance found that efavirenz-based treatment led to a shorter mean time to undetectable viral load. A higher proportion of patients with nonnucleoside reverse transcriptase inhibitor related baseline resistance mutations in the efavirenz-treatment group achieved an undetectable viral load at both 6 and 12 months post-treatment initiation, compared with the boosted protease-inhibitor-treatment group.Supplementary content: http://links.lww.com/QAD/A930. PMID:27139315

  8. New Antiretroviral Treatment for HIV.

    PubMed

    Badowski, Melissa E; Pérez, Sarah E; Biagi, Mark; Littler, John A

    2016-09-01

    The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set the global goal of ending the AIDS world epidemic by 2030. In order to end this epidemic they have established a 90-90-90 goal to be achieved by 2020, which may be problematic, especially in low- and middle-income countries. This goal includes 90% of individuals with HIV globally being diagnosed, on treatment, and virologically suppressed. Based on global estimates from 2014-2015, approximately 36.9 million individuals are living with HIV. Of those, 53% have been diagnosed with HIV, 41% are on antiretroviral therapy (ART), and 32% have viral suppression with <1000 copies/ml. Comprehensive approaches are needed to improve the number of people living with HIV (PLWH) who are diagnosed, linked, and engaged in care. Once PLWH are retained in care, treatment is key to both HIV prevention and transmission. The development and advancement of new ART is necessary to assist in reaching these goals by improving safety profiles, decreasing pill burden, improving quality of life and life expectancy, and creating new mechanisms to overcome resistance. The focus of this review is to highlight and review data for antiretroviral agents recently added to the market as well as discuss agents in various stages of development (new formulations and mechanisms of action). PMID:27539455

  9. Combination Antiretroviral Use and Preterm Birth

    PubMed Central

    Watts, D. Heather; Williams, Paige L.; Kacanek, Deborah; Griner, Raymond; Rich, Kenneth; Hazra, Rohan; Mofenson, Lynne M.; Mendez, Hermann A.

    2013-01-01

    Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)–exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics. Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens. Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity. PMID:23204173

  10. Combination antiretroviral studies for patients with primary biliary cirrhosis

    PubMed Central

    Lytvyak, Ellina; Montano-Loza, Aldo J; Mason, Andrew L

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label

  11. Predicting virological decay in patients starting combination antiretroviral therapy

    PubMed Central

    2016-01-01

    Objective: Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART. Design: Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study). Methods: Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance. Results: Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one. Conclusions: Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART. PMID:27124894

  12. [Lopinavir/ritonavir in new initial antiretroviral treatment strategies].

    PubMed

    Rolón, María José; Figueroa, María Inés; Sued, Omar; Cahn, Pedro

    2014-11-01

    According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.

  13. Safety and Effectiveness of Combination Antiretroviral Therapy during the First Year of Treatment in HIV-1 Infected Rwandan Children: A Prospective Study

    PubMed Central

    Mutwa, Philippe R.; Boer, Kimberly R.; Asiimwe-Kateera, Brenda; Tuyishimire, Diane; Muganga, Narcisse; Lange, Joep M. A.; van de Wijgert, Janneke; Asiimwe, Anita; Reiss, Peter; Geelen, Sibyl P. M.

    2014-01-01

    Background With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed. Methods HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration. Clinical success was defined as WAZ and WAZ >−2, immunological success as CD4 cells ≥500/mm3 and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration <40 copies/mL. Results Between March 2008 and December 2009, 123 HIV-infected children were included. The median (interquartile (IQR) age at cART initiation was 7.4 (3.2, 11.5) years; 40% were <5 years and 54% were female. Mean (95% confidence interval (95%CI)) HAZ and WAZ at baseline were −2.01 (−2.23, −1.80) and −1.73 (−1.95, −1.50) respectively and rose to −1.75 (−1.98, −1.51) and −1.17 (−1.38, −0.96) after 12 months of cART. The median (IQR) CD4 T-cell values for children <5 and ≥5 years of age were 20% (13, 28) and 337 (236, 484) cells/mm3respectively, and increased to 36% (28, 41) and 620 (375, 880) cells/mm3. After 12 months of cART, 24% of children had a detectable viral load, including 16% with virological failure (HIV-RNA>1000 c/mL). Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33%) of children had side effects (by self-report or clinical assessment), but only 9% experienced a severe side effect requiring a cART regimen change. Conclusions cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as

  14. Impact of earlier combination antiretroviral therapy on outcomes in children

    PubMed Central

    Cotton, Mark F.; Rabie, Helena

    2015-01-01

    Purpose of review Early initiation of combination antiretroviral therapy (ART) in infants below 12 weeks of age reduces morbidity and mortality. A recent report of transient HIV remission in a child beginning ART from the second day of life has focused attention on very early therapy in the first days of life. Recent findings In the randomized children with HIV, early antiretroviral limited ART beginning at a median of 7.4 weeks of age lowered mortality and disease progression significantly compared with deferred ART beginning at a median of 21 weeks on study. In high-burden settings, infants initiating ART appear sicker than in children with HIV early antiretroviral and start at a later age. Many could be diagnosed on the first day of life. There are still programmatic obstacles to early diagnosis and initiation of ART in high-burden settings. There is growing but insufficient information on ART dosages in newborn infants. Summary There is now increased focus on initiating ART as postexposure prophylaxis in newborn infants at high risk of vertical transmission in the hope of limiting morbidity and dissemination of the virus. PMID:25389804

  15. Economics of antiretroviral treatment vs. circumcision for HIV prevention.

    PubMed

    Bärnighausen, Till; Bloom, David E; Humair, Salal

    2012-12-26

    The HIV Prevention Trials Network (HPTN) 052 study, which showed the effectiveness of antiretroviral treatment in reducing HIV transmission, has been hailed as a "game changer" in the fight against HIV, prompting calls for scaling up treatment as prevention (TasP). However, it is unclear how TasP can be financed, given flat-lining support for global HIV programs. We assess whether TasP is indeed a game changer or if comparable benefits are obtainable at similar or lower cost by increasing coverage of medical male circumcision (MMC) and antiretroviral treatment (ART) at CD4 <350/μL. We develop a new mathematical model and apply it to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009-2020. MMC outperforms ART significantly in cost per infection averted ($1,096 vs. $6,790) and performs comparably in cost per death averted ($5,198 vs. $5,604). TasP is substantially less cost effective at $8,375 per infection and $7,739 per death averted. The prevention benefits of HIV treatment are largely reaped with high ART coverage. The most cost-effective HIV prevention strategy is to expand MMC coverage and then scale up ART, but the most cost-effective HIV-mortality reduction strategy is to scale up MMC and ART jointly. TasP is cost effective by commonly used absolute benchmarks but it is far less cost effective than MMC and ART. Given South Africa's current annual ART spending, the $5 billion in savings offered by MMC and ART over TasP in the next decade, for similar health benefits, challenges the widely hailed status of TasP as a game changer.

  16. The (political) economics of antiretroviral treatment in developing countries.

    PubMed

    Nattrass, Nicoli J

    2008-12-01

    Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART.

  17. What's new for antiretroviral treatment in women with HIV.

    PubMed

    Andany, Nisha; Walmsley, Sharon L

    2016-01-01

    Currently, women represent 52% of persons infected with HIV worldwide and 23% of those in the United States. Combination antiretroviral therapy (cART) has resulted in remarkable reductions in HIV-associated morbidity and mortality, and has dramatically improved life expectancy. Treatment guidelines do not differ for HIV-infected men and non-pregnant women. However, clinical trials of antiretroviral agents have limited female enrolment, and results from these predominantly male studies are extrapolated to the female population. Furthermore, many of these studies do not report gender subgroup analyses, and those that do are underpowered to detect differences between men and women, limiting the ability to assess if results are equally applicable to both sexes. Women may have differential responses to and adverse events from cART. A limited number of female-only clinical trials have demonstrated that female recruitment and retention in these studies is feasible. Therefore, urgent attention is required to improve the body of knowledge regarding clinical efficacy, safety and tolerability of cART in women. In particular, women living with HIV are faced with various sexual and reproductive health concerns that may influence choice of cART. These include potential interactions with hormonal contraception, safety in pregnancy, and the impact of the transition through menopause and development of age-related comorbidities. Finally, the ongoing advances in biomedical HIV prevention, particularly pre-exposure prophylaxis (PrEP), provide an enormous opportunity to enhance HIV prevention in high-risk women, in efforts to further reduce global burden of the pandemic. PMID:27482438

  18. The obligation to provide antiretroviral treatment in HIV prevention trials.

    PubMed

    Lo, Bernard; Padian, Nancy; Barnes, Mark

    2007-06-19

    Providing antiretroviral therapy (ART) to participants who seroconvert during HIV prevention trials in developing countries is an ethical expectation. Promising treatment to the few seroconverters widens disparities within a resource-poor country and would be unjust. Such an assurance should be done in a way that also improves access to ART for others in the country. US funds for ART in poor countries from the PEPFAR should be available to all countries that host HIV prevention and clinical trials. PMID:17545698

  19. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

    PubMed Central

    Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John; Cambiano, Valentina; Chindelevitch, Leonid; Cori, Anne; Hontelez, Jan A C; Humair, Salal; Kerr, Cliff C; Klein, Daniel J; Mishra, Sharmistha; Mitchell, Kate M; Nichols, Brooke E; Vickerman, Peter; Bakker, Roel; Bärnighausen, Till; Bershteyn, Anna; Bloom, David E; Boily, Marie-Claude; Chang, Stewart T; Cohen, Ted; Dodd, Peter J; Fraser, Christophe; Gopalappa, Chaitra; Lundgren, Jens; Martin, Natasha K; Mikkelsen, Evelinn; Mountain, Elisa; Pham, Quang D; Pickles, Michael; Phillips, Andrew; Platt, Lucy; Pretorius, Carel; Prudden, Holly J; Salomon, Joshua A; van de Vijver, David A M C; de Vlas, Sake J; Wagner, Bradley G; White, Richard G; Wilson, David P; Zhang, Lei; Blandford, John; Meyer-Rath, Gesine; Remme, Michelle; Revill, Paul; Sangrujee, Nalinee; Terris-Prestholt, Fern; Doherty, Meg; Shaffer, Nathan; Easterbrook, Philippa J; Hirnschall, Gottfried; Hallett, Timothy B

    2014-01-01

    Background New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. Methods We used multiple independent mathematical models in four settings—South Africa, Zambia, India, and Vietnam—to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered ‘very cost-effective’ if the $/DALY was less than the country’s per capita gross domestic product (GDP; South Africa: $8040, Zambia: $1425, India: $1489, Vietnam: $1407) and ‘cost-effective’ if $/DALY was less than three times per capita GDP. Findings In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from $237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to $749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to $241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost

  20. [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.

  1. [Positioning of lopinavir/ritonavir in antiretroviral treatment schemes].

    PubMed

    Camacho, Ángela; Rivero, Antonio

    2014-11-01

    Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission.

  2. Approaches to rationing antiretroviral treatment: ethical and equity implications.

    PubMed Central

    Bennett, Sara; Chanfreau, Catherine

    2005-01-01

    Despite a growing global commitment to the provision of antiretroviral therapy (ART), its availability is still likely to be less than the need. This imbalance raises ethical dilemmas about who should be granted access to publicly-subsidized ART programmes. This paper reviews the eligibility and targeting criteria used in four case-study countries at different points in the scale-up of ART, with the aim of drawing lessons regarding ethical approaches to rationing. Mexico, Senegal, Thailand and Uganda have each made an explicit policy commitment to provide antiretrovirals to all those in need, but are achieving this goal in steps--beginning with explicit rationing of access to care. Drawing upon the case-studies and experiences elsewhere, categories of explicit rationing criteria have been identified. These include biomedical factors, adherence to treatment, prevention-driven factors, social and economic benefits, financial factors and factors driven by ethical arguments. The initial criteria for determining eligibility are typically clinical criteria and assessment of adherence prospects, followed by a number of other factors. Rationing mechanisms reflect several underlying ethical theories and the ethical underpinnings of explicit rationing criteria should reflect societal values. In order to ensure this alignment, widespread consultation with a variety of stakeholders, and not only policy-makers or physicians, is critical. Without such explicit debate, more rationing will occur implicitly and this may be more inequitable. The effects of rationing mechanisms upon equity are critically dependent upon the implementation processes. As antiretroviral programmes are implemented it is crucial to monitor who gains access to these programmes. PMID:16175829

  3. Modulation of HCV Replication After Combination Antiretroviral Therapy in HCV/HIV Coinfected Patients

    PubMed Central

    Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.

    2015-01-01

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888

  4. Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

    PubMed Central

    Kaleebu, Pontiano; Kirungi, Wilford; Watera, Christine; Asio, Juliet; Lyagoba, Fred; Lutalo, Tom; Kapaata, Anne A.; Nanyonga, Faith; Parry, Chris M.; Magambo, Brian; Nazziwa, Jamirah; Nannyonjo, Maria; Hughes, Peter; Hladik, Wolfgang; Ruberantwari, Anthony; Namuwenge, Norah; Musinguzi, Joshua; Downing, Robert; Katongole-Mbidde, Edward

    2015-01-01

    Background With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). Methods We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. Results Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/μl (AOR 2.80, 95% CI: 1.08–7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14). Conclusion Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs. PMID:26700639

  5. Platelet count kinetics following interruption of antiretroviral treatment

    PubMed Central

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V.; Somboonwit, Charurut; Llibre, Josep M.; Palfreeman, Adrian; Chini, Maria; Lundgren, Jens D.

    2014-01-01

    Objectives To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. Design SMART patients from sites that determined platelets routinely. Methods Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. Results Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: −24 000/µl (−54 000 to 4000) vs. 3000 (−22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/µl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2–2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = −0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. Conclusion Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study. PMID:23018440

  6. Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges

    PubMed Central

    Wester, C William; Bussmann, Hermann; Koethe, John; Moffat, Claire; Vermund, Sten; Essex, Max; Marlink, Richard G

    2009-01-01

    Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment. Analyses from the region report favorable clinical/treatment outcomes and impressive declines in AIDS-related mortality among HIV-1-infected adults and children receiving cART. While immunologic recovery, virologic suppression and cART adherence rates are on par with resource-rich settings, loss to follow-up and high mortality rates, especially within the first 6 months of treatment, remain a significant problem. Over the next decade, cART coverage rates are expected to improve across the region, with attendant increases in healthcare utilization for HIV- and non-HIV-related complications and the need for expanded laboratory and clinical services. Planned and in-progress trials will evaluate the use of cART to prevent primary HIV-1 infection with so-called ‘test and treat’ expansions of coverage and treatment. Education and training programs as well as patient-retention strategies will need to be strengthened as national cART programs are expanded and more people require lifelong monitoring and care. PMID:20161344

  7. Antiretroviral treatment induced catatonia in 16-year-old boy.

    PubMed

    Lingeswaran, Anand

    2014-01-01

    We present a 16-year-old boy, who had presented to us with catatonic features of mutism, withdrawal, passive negativism, grimacing, gesturing, echopraxia, and excitement of 5 days duration while taking antiretroviral therapy (ART) for a period of 2 years. He had history of birth asphyxia and acquired HIV infection from his father when the same syringe and needle was used on both of them in a medical setting where the father and son had consulted for treatment of pyrexia of unknown origin. He was the eldest of a three children family in which the biologic father had acquired HIV through extramarital sexual contact with HIV-infected sex workers but was unaware of his HIV positive status till our patient, the 16-year-old was admitted and treated for pulmonary tuberculosis at 14 years of age. The boy's mother had only acquired HIV after having three children with the HIV-positive husband, thus leaving the other two children HIV negative. The catatonia completely resolved within 2 days after the ART was withheld, and risperidone 1 mg twice a day was prescribed. This case highlights the risks of ART and breach of universal precautions.

  8. Antiretroviral Treatment is Associated with Increased Attentional Load-Dependent Brain Activation in HIV Patients

    PubMed Central

    Chang, L.; Yakupov, R.; Nakama, H.; Stokes, B.; Ernst, T.

    2009-01-01

    Objective The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Methods Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n=18), HIV subjects treated with antiretroviral medications (HIV+ ARV, n=12), or not treated with antiretroviral medications (HIV+NARV, n=12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. Results HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected=0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected=0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. Interpretation These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention. PMID:18247124

  9. Predictors of Antiretroviral Treatment Failure in an Urban HIV Clinic

    PubMed Central

    Robbins, Gregory K.; Daniels, Brock; Zheng, Hui; Chueh, Henry; Meigs, James B.; Freedberg, Kenneth A.

    2008-01-01

    Background Predictors of antiretroviral treatment (ART) failure are not well characterized for heterogeneous clinic populations. Methods A retrospective analysis was conducted of HIV-infected patients followed in an urban HIV clinic with an HIV RNA measurement ≤400 copies/mL on ART between January 1, 2003, and December 31, 2004. The primary endpoint was treatment failure, defined as virologic failure (≥1 HIV RNA measurement >400 copies/mL), unsanctioned stopping of ART, or loss to follow-up. Prior ART adherence and other baseline patient characteristics, determined at the time of the first suppressed HIV RNA load on or after January 1, 2003, were extracted from the electronic health record (EHR). Predictors of failure were assessed using proportional hazards modeling. Results Of 829 patients in the clinic, 614 had at least 1 HIV RNA measurement ≤400 copies/mL during the study period. Of these, 167 (27.2%) experienced treatment failure. Baseline characteristics associated with treatment failure in the multivariate model were: poor adherence (hazard ratio [HR] = 3.44; 95% confidence interval [CI]: 2.34 to 5.05), absolute neutrophil count <1000/mm3 (HR = 2.90, 95% CI: 1.26 to 6.69), not suppressed on January 1, 2003 (HR = 2.69, 95% CI: 1.78 to 4.07) or <12 months of suppression (HR = 1.64, 95% CI: 1.10 to 2.45), CD4 count <200 cells/mm3 (HR = 1.90, 95% CI: 1.31 to 2.76), nucleoside-only regimen (HR = 1.75, 95% CI: 1.08 to 2.82), prior virologic failure (HR = 1.70, 95% CI: 1.22 to 2.39) and ≥1 missed visit in the prior year (HR = 1.56, 95% CI: 1.13 to 2.16). Conclusions More than one quarter of patients in a heterogeneous clinic population had treatment failure over a 2-year period. Prior ART adherence and other EHR data readily identify patient characteristics that could trigger specific interventions to improve ART outcomes. PMID:17106280

  10. Highly active antiretroviral treatment for the prevention of HIV transmission

    PubMed Central

    2010-01-01

    In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV. Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment. HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART. Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability

  11. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

    PubMed Central

    Corbett, Elizabeth L.; Connor, Myles D.; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C.A.; Bryer, Alan; Faragher, Brian; Heyderman, Robert S.; Allain, Theresa J.; Solomon, Tom

    2016-01-01

    Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43–12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44–8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21–46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID:26683649

  12. Predictors of New Onset Distal Neuropathic Pain in HIV-infected Individuals in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Malvar, Jemily; Vaida, Florin; Sanders, Chelsea Fitzsimons; Atkinson, J. Hampton; Bohannon, William; Keltner, John; Robinson-Papp, Jessica; Simpson, David M.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin; Fan, Juanjuan; Grant, Igor; Ellis, Ronald J.

    2015-01-01

    Despite modern combination antiretroviral therapy (CART), distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semi-annual clinical evaluations were administered at six U.S. sites. DNP was defined by using a clinician-administered instrument standardized across sites. All participants analyzed were free of DNP at study entry. New onset DNP was recorded at the first follow-up visit at which it was reported. Mixed effects logistic regression was used to evaluate potential predictors including HIV disease and treatment factors, demographics, medical comorbidities and neuropsychiatric factors. Among 493 participants, 131 (27%) reported new DNP over 2,306 visits during a median follow-up of 24 months [interquartile range (IQR) 12-42]. In multivariable regression, after adjusting for other covariates, significant entry predictors of new DNP were older age, female sex, current and past antiretroviral treatment, lack of virologic suppression, and lifetime history of opioid use disorder. During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a prior history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood. PMID:25659067

  13. Antiretroviral drug resistance among antiretroviral-naïve and treatment experienced patients infected with HIV in Iran.

    PubMed

    Baesi, Kazem; Ravanshad, Mehrdad; Ghanbarisafari, Maryam; Saberfar, Esmaeil; Seyedalinaghi, Seyedahmad; Volk, Jonathan E

    2014-07-01

    Resistance to antiretroviral therapy (ART) threatens the success of programs to reduce HIV morbidity and mortality, particularly in countries with few treatment options. In the present study, genotype and phenotype data from ART-naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High-level resistance to efavirenz (EFV) was more common among participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P < 0.0001). Two (6.7%) antiretroviral-naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed.

  14. Short-term risk of anaemia following initiation of combination antiretroviral treatment in HIV-infected patients in countries in sub-Saharan Africa, Asia-Pacific, and central and South America

    PubMed Central

    2012-01-01

    Background The objective was to examine the short-term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV-infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration. Methods Anaemia was defined as haemoglobin of < 10 g/dL. Patients were included if they started cART with three or more drugs, had prior haemoglobin of > = 10 g/dL, and had one or more follow-up haemoglobin tests. Factors associated with anaemia up to 12 months were examined using Cox proportional hazards models and stratified by IeDEA region. Results Between 1998 and 2008, 19,947 patients initiated cART with baseline and follow-up haemoglobin tests (7358, 7289, 2853, 471, 1550 and 426 in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions, respectively). At initiation, anaemia was found in 45% of Western Africa patients, 29% of Eastern Africa patients, 21% of Southern Africa patients, 36% of Central Africa patients, 15% of patients in Asian-Pacific and 14% of patients in Caribbean and Central and South America. Among patients with haemoglobin of > = 10 g/dL at baseline (13,445), the risks of anaemia were 18.2, 6.6, 9.7, 22.9, 11.8 and 19.5 per 100 person-years in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian, and Caribbean and Central and South America regions, respectively. Factors associated with anaemia were female sex, low baseline haemoglobin level, low baseline CD4 count, more advanced disease stage, and initial cART containing zidovudine. Conclusions In data from 34 cohorts of HIV-infected patients from sub-Saharan Africa, Central and South America, and Asia, the risk of anaemia within 12 months of initiating cART was moderate. Routine haemoglobin

  15. Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

    PubMed Central

    May, Margaret T.; Vehreschild, Jorg-Janne; Trickey, Adam; Obel, Niels; Reiss, Peter; Bonnet, Fabrice; Mary-Krause, Murielle; Samji, Hasina; Cavassini, Matthias; Gill, Michael John; Shepherd, Leah C.; Crane, Heidi M.; d'Arminio Monforte, Antonella; Burkholder, Greer A.; Johnson, Margaret M.; Sobrino-Vegas, Paz; Domingo, Pere; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy R.; Miró, José M.; Sterne, Jonathan A. C.

    2016-01-01

    Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5–0.9, 1–2.9, 3–4.9, 5–9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996–2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996–1997, 1998–1999, 2000–2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0–49, 50–99, 100–199, 200–349, 350–499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2–35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4–16.8) during 5–9.9 years and 14.2 (95% CI, 13.3–15.1) after 10 years’ duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94–1.00; P = .054) and 1.02 (95% CI, .98–1.07; P = .32) among patients followed for 5–9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. PMID:27025828

  16. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    SciTech Connect

    Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

    2007-10-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF{sub 2{alpha}}) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF{sub 2{alpha}} production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and

  17. Challenges of malnutrition care among HIV-infected children on antiretroviral treatment in Africa.

    PubMed

    Jesson, J; Leroy, V

    2015-05-01

    More than 90% of the estimated 3.2 million children with HIV worldwide, at the end of 2013, were living in sub-Saharan Africa. The management of these children was still difficult in 2014 despite the progress in access to antiretroviral drugs. A great number of HIV-infected children are not diagnosed at 6 weeks and start antiretroviral treatment late, at an advanced stage of HIV disease complicated by other comorbidities such as malnutrition. Malnutrition is a major problem in the sub-Saharan Africa global population; it is an additional burden for HIV-infected children because they do not respond as well as non-infected children to the usual nutritional care. HIV infection and malnutrition interact, creating a vicious circle. It is important to understand the relationship between these 2 conditions and the effect of antiretroviral treatment on this circle to taking them into account for an optimal management of pediatric HIV. An improved monitoring of growth during follow-up and the introduction of a nutritional support among HIV-infected children, especially at antiretroviral treatment initiation, are important factors that could improve response to antiretroviral treatment and optimize the management of pediatric HIV in resource-limited countries. PMID:25861689

  18. Challenges of malnutrition care among HIV-infected children on antiretroviral treatment in Africa.

    PubMed

    Jesson, J; Leroy, V

    2015-05-01

    More than 90% of the estimated 3.2 million children with HIV worldwide, at the end of 2013, were living in sub-Saharan Africa. The management of these children was still difficult in 2014 despite the progress in access to antiretroviral drugs. A great number of HIV-infected children are not diagnosed at 6 weeks and start antiretroviral treatment late, at an advanced stage of HIV disease complicated by other comorbidities such as malnutrition. Malnutrition is a major problem in the sub-Saharan Africa global population; it is an additional burden for HIV-infected children because they do not respond as well as non-infected children to the usual nutritional care. HIV infection and malnutrition interact, creating a vicious circle. It is important to understand the relationship between these 2 conditions and the effect of antiretroviral treatment on this circle to taking them into account for an optimal management of pediatric HIV. An improved monitoring of growth during follow-up and the introduction of a nutritional support among HIV-infected children, especially at antiretroviral treatment initiation, are important factors that could improve response to antiretroviral treatment and optimize the management of pediatric HIV in resource-limited countries.

  19. Financing equitable access to antiretroviral treatment in South Africa

    PubMed Central

    2010-01-01

    Background While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART). South Africa is currently debating the introduction of a National Health Insurance (NHI) system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020. Methods The costs of ART and universal coverage (UC) are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices. Results The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model) and the annual costs of ART would not exceed 15% of the universal health system budget. Conclusions Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the introduction of a

  20. Recent trends in early stage response to combination antiretroviral therapy in Australia

    PubMed Central

    McManus, Hamish; Hoy, Jennifer F; Woolley, Ian; Boyd, Mark A; Kelly, Mark D; Mulhall, Brian; Roth, Norman J; Petoumenos, Kathy; Law, Matthew G

    2014-01-01

    Background There have been improvements in combination antiretroviral therapy (cART) over the last 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome. Methods Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4+ and the proportion of patients with detectable HIV viral load (>400 copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method. Results 2,753 patients were included in the analysis: 28% initiated treatment <1996 using mono/duo therapy; and 72% initiated treatment ≥1996 using cART (30% 1996–99; 12% 2000–03; 11% 2004–07; and 19% ≥2008). Overall CD4 response improved by later era of initiation (p<0.001), although 2000–03 CD4 response was less than that for 1996–99 (p=0.007). The average proportion with detectable viral load from 2 to 4 years post treatment commencement by era was: <1996 mono/duo 0.69 (0.67–0.71); 1996–99 cART 0.29 (0.28–0.30); 2000–03 cART 0.22 (0.20–0.24); 2004–07 cART 0.09 (0.07–0.10); ≥2008 cART 0.04 (0.03–0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996–99 to 29% after 2008 (p<0.001). Conclusions Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4 count), and also increased durability of first-line ART regimens. PMID:24704818

  1. Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

    PubMed Central

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

    2013-01-01

    Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and—if successful—to galvanise treatment as prevention. PMID:24152938

  2. Impact of Extended Combination Antiretroviral Therapy on the Decline of HIV Prevalence in Pregnant Women in Malawi.

    PubMed

    Liotta, Giuseppe; Chimbwandira, Frank; Wouters, Kristien; Nielsen-Saines, Karin; Jere, Haswell; Mancinelli, Sandro; Ceffa, Susanna; Erba, Fulvio; Palombi, Leonardo; Marazzi, Maria Cristina

    2016-01-01

    Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women.

  3. Combination of Antiretroviral Drugs and Radioimmunotherapy Specifically Kills Infected Cells from HIV-Infected Individuals

    PubMed Central

    Tsukrov, Dina; McFarren, Alicia; Morgenstern, Alfred; Bruchertseifer, Frank; Dolce, Eugene; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Berman, Joan W.; Schoenbaum, Ellie; Zingman, Barry S.; Casadevall, Arturo; Dadachova, Ekaterina

    2016-01-01

    Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT), a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infected cells. Since gp41 expression by infected cells is likely downregulated in patients on antiretroviral therapy (ART), we evaluated the ability of RIT to kill ART-treated infected cells using both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs) were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal antibody to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: 10 on ART and 5 ART-naïve. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART and supports continued development of 213Bi-2556 for co-administration with ART toward an HIV eradication strategy. PMID:27725930

  4. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging.

    PubMed

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets.

  5. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging.

    PubMed

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID:26273190

  6. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

    PubMed Central

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID:26273190

  7. Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen

    2015-01-01

    Objectives This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. Methods We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. Results During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12–35.16) and older age (AOR, 1.04; 95% CI, 1.00–1.09). The positive association between duration of exposure to ritonavir

  8. Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review.

    PubMed

    Hsu, Emory; Phadke, Varun K; Nguyen, Minh Ly T

    2016-06-01

    We describe an HIV-infected patient initiated on combined antiretroviral therapy (cART) who subsequently developed immune restoration disease (IRD) hyperthyroidism-this case represents one of five such patients seen at our center within the past year. Similar to previous reports of hyperthyroidism due to IRD, all of our patients experienced a rapid early recovery in total CD4 count, but developed symptoms of hyperthyroidism on average 3 years (38 months) after beginning cART, which represents a longer time frame than previously reported. Awareness and recognition of this potential complication of cART, which may occur years after treatment initiation, will allow patients with immune restorative hyperthyroidism to receive timely therapy and avoid the long-term complications associated with undiagnosed thyroid disease. PMID:26887978

  9. Effects of combination antiretroviral therapies on the risk for myocardial infarction among HIV patients

    PubMed Central

    Brouwer, Emily S.; Napravnik, Sonia; Eron, Joseph J; Stalzer, Brant; Floris-Moore, Michelle; Simpson, Ross J; Stürmer, Til

    2014-01-01

    Background Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating a randomized controlled trial comparing initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI. Methods We included North Carolina (NC) Medicaid beneficiaries infected with HIV between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) recipients. We adjusted for confounding through inverse-probability-weighting methods. Results There were 3,481 NC Medicaid new cART recipients who contributed 6,399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI unadjusted (HR= 2.70 [95% CI= 1.24 - 5.91]; HR= 2.05 [0.72 - 5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although, estimates were imprecise. Conclusions We found an increased rate of MI among patients initiating abacavir compared with tenofovir although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association. PMID:24713880

  10. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  11. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

    PubMed Central

    2011-01-01

    Summary Background Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. Methods The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude death rates were also calculated. Findings 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude death rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than men. Patients with presumed transmission via injecting drug use had lower life expectancies than those from other transmission groups (32·6 [1·1] years vs 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 counts than in those with higher baseline counts

  12. Tuberculosis After One Year of Combination Antiretroviral Therapy in Nigeria: A Retrospective Cohort Study

    PubMed Central

    Achenbach, Chad J.; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T.; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L.

    2013-01-01

    Abstract Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm3 and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm3 and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count <350 cells/mm3 and HIV-1 RNA level ≤400 copies/ml (group 3), and CD4 T cell count <350 cells/mm3 and HIV-1 RNA level >400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan–Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97–4.61), 2.05 (95% CI 1.10–3.79), and 3.65 (95% CI 1.15–5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population. PMID:23316724

  13. Tuberculosis after one year of combination antiretroviral therapy in Nigeria: a retrospective cohort study.

    PubMed

    Akanbi, Maxwell O; Achenbach, Chad J; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L

    2013-06-01

    Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count <350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 3), and CD4 T cell count <350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan-Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97-4.61), 2.05 (95% CI 1.10-3.79), and 3.65 (95% CI 1.15-5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population.

  14. HIV Care and Treatment Beliefs among Patients Initiating Antiretroviral Treatment (ART) in Oromia, Ethiopia.

    PubMed

    Tymejczyk, Olga; Hoffman, Susie; Kulkarni, Sarah Gorrell; Gadisa, Tsigereda; Lahuerta, Maria; Remien, Robert H; Elul, Batya; El-Sadr, Wafaa; Melaku, Zenebe; Nash, Denis

    2016-05-01

    To better understand patient beliefs, which may influence adherence to HIV care and treatment, we examined three dimensions of beliefs among Ethiopian adults (n = 1177) initiating antiretroviral therapy (ART). Beliefs about benefits of ART/HIV clinical care were largely accurate, but few patients believed in the ability of ART to prevent sexual transmission and many thought Holy Water could cure HIV. Factors associated with lower odds of accurate beliefs included advanced HIV, lack of formal education, and Muslim religion (benefits of ART/clinical care); secondary or university education and more clinic visits (ART to prevent sexual transmission); and pregnancy and Orthodox Christian religion (Holy Water). Assessment of patient beliefs may help providers identify areas needing reinforcement. In this setting, counselors also need to stress the benefits of ART as prevention and that Holy Water should not be used to the exclusion of HIV care and ART.

  15. 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

  16. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children

    PubMed Central

    Parikh, Sunil; Kajubi, Richard; Huang, Liusheng; Ssebuliba, Joshua; Kiconco, Sylvia; Gao, Qin; Li, Fangyong; Were, Moses; Kakuru, Abel; Achan, Jane; Mwebaza, Norah; Aweeka, Francesca T.

    2016-01-01

    Background. The optimal treatment of malaria in human immunodeficiency virus (HIV)–infected children requires consideration of critical drug–drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes. Methods. We conducted an intensive and sparse pharmacokinetic/pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on 3 different first-line antiretroviral therapy (ART) regimens were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin, and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated. Results. One hundred forty-five and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared with no ART, efavirenz (EFV) reduced exposure to all antimalarial components by 2.1- to 3.4-fold; lopinavir/ritonavir (LPV/r) increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on EFV vs LPV/r-based ART, changes that were associated with an approximate 4-fold higher odds of recurrent malaria by day 28 in those on EFV vs LPV/r-based ART. Conclusions. The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. EFV-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on EFV, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure, is warranted. PMID:27143666

  17. [Dietary intake and dyslipidemia arising from combination antiretroviral therapy for HIV infection: a systematic review].

    PubMed

    Almeida, Luara Bellinghausen; Giudici, Kelly Virecoulon; Jaime, Patricia Constante

    2009-07-01

    To review and synthesize the available scientific evidence on the relationship between dietary intake and dyslipidemias in HIV-infected patients in combination antiretroviral therapy (ART). A systematic review of literature was carried out. Original and published studies were investigated and two categories of dietary exposure were considered: energy and nutrient intake, and consumption of a test diet. A narrative review of included studies was conducted. The findings were summarized according to category of metabolic outcomes (effect on total cholesterol and LDL-c, effect on HDL-c and effect on triglycerides). Twenty original studies were included in this review, being 13 clinical trials and 7 observational studies. Omega-3 fatty acid supplementation led to a significant decrease in triglycerides. There was very little evidence on the effectiveness of dietary interventions for the prevention and control of dyslipidemias in HIV-infected patients receiving ART.

  18. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy

    PubMed Central

    Rizzardi, G. Paolo; Harari, Alexandre; Capiluppi, Brunella; Tambussi, Giuseppe; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Chave, Jean-Philippe; Lazzarin, Adriano; Pantaleo, Giuseppe

    2002-01-01

    Primary HIV-1 infection causes extensive immune activation, during which CD4+ T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4+ T cell levels, both in terms of percentage and absolute numbers. The increase in CD4+ T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8+ or CD4+ T cell responses. At week 48, the proportion of IFN-γ–secreting CD4+ and CD4+CCR7– T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection. PMID:11877476

  19. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  20. Global challenges in the development and delivery of paediatric antiretrovirals.

    PubMed

    Bowen, Asha; Palasanthiran, Pamela; Sohn, Annette H

    2008-06-01

    By the end of 2006, compared with 28% coverage for adults, only 15% of children with HIV that needed antiretroviral treatment were receiving it. Major challenges in delivering treatment include the lack of paediatric antiretrovirals that can be dosed in small children and limited studies examining safety and efficacy for existing antiretroviral formulations. The high costs of treatment have been reduced through the use of generic, fixed-dose combination drugs. Evidence-based strategies for managing resistance and the scale-up of pharmacological trials for children in low- and middle-income countries are crucial to the success and future development of paediatric antiretrovirals.

  1. Formulation and Characterization of Polymeric Films Containing Combinations of Antiretrovirals (ARVs) for HIV Prevention

    PubMed Central

    Akil, Ayman; Agashe, Hrushikesh; Dezzutti, Charlene S.; Moncla, Bernard J.; Hillier, Sharon L.; Devlin, Brid; Shi, Yuan; Uranker, Kevin; Rohan, Lisa Cencia

    2014-01-01

    Purpose To develop polymeric films containing dual combinations of anti-HIV drug candidate tenofovir, maraviroc and dapivirine for vaginal application as topical microbicides. Methods A solvent casting method was used to manufacture the films. Solid phase solubility was used to identify potential polymers for use in the film formulation. Physical and chemical properties (such as water content, puncture strength and in vitro release) and product stability were determined. The bioactivity of the film products against HIV was assessed using the TZM-bl assay and a cervical explant model. Results Polymers identified from the solid phase solubility study maintained tenofovir and maraviroc in an amorphous state and prevented drug crystallization. Three combination film products were developed using cellulose polymers and polyvinyl alcohol. The residual water content in all films was < 10% (w/w). All films delivered the active agents with release of > 50% of film drug content within 30 minutes. Stability testing confirmed that the combination film products were stable for 12 months at ambient temperature and 6 months under stressed conditions. Antiviral activity was confirmed in TZM-bl and cervical explant models. Conclusions Polymeric films can be used as a stable dosage form for the delivery of antiretroviral combinations as microbicides. PMID:25079391

  2. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice

    PubMed Central

    Horwitz, Joshua A.; Halper-Stromberg, Ariel; Mouquet, Hugo; Gitlin, Alexander D.; Tretiakova, Anna; Eisenreich, Thomas R.; Malbec, Marine; Gravemann, Sophia; Billerbeck, Eva; Dorner, Marcus; Büning, Hildegard; Schwartz, Olivier; Knops, Elena; Kaiser, Rolf; Seaman, Michael S.; Wilson, James M.; Rice, Charles M.; Ploss, Alexander; Bjorkman, Pamela J.; Klein, Florian; Nussenzweig, Michel C.

    2013-01-01

    Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1–infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice. PMID:24043801

  3. The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial

    PubMed Central

    Howard, Andrea A.; Hirsch-Moverman, Yael; Frederix, Koen; Daftary, Amrita; Saito, Suzue; Gross, Tal; Wu, Yingfeng; Maama, Llang Bridget

    2016-01-01

    Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START

  4. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy.

    PubMed

    Del Prete, Gregory Q; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W Gregory; Trubey, Charles M; Piatak, Michael; Deleage, Claire; Keele, Brandon F; Estes, Jacob D; Hesselgesser, Joseph; Geleziunas, Romas; Lifson, Jeffrey D

    2016-03-01

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4(+) T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy. PMID:26711758

  5. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy

    PubMed Central

    Del Prete, Gregory Q.; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W. Gregory; Trubey, Charles M.; Piatak, Michael; Deleage, Claire; Keele, Brandon F.; Estes, Jacob D.; Hesselgesser, Joseph; Geleziunas, Romas

    2015-01-01

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4+ T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy. PMID:26711758

  6. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy.

    PubMed

    Del Prete, Gregory Q; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W Gregory; Trubey, Charles M; Piatak, Michael; Deleage, Claire; Keele, Brandon F; Estes, Jacob D; Hesselgesser, Joseph; Geleziunas, Romas; Lifson, Jeffrey D

    2015-12-28

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4(+) T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy.

  7. Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

    PubMed

    Geffen, N; Aagaard, P; Corbelli, G M; Meulbroek, M; Peavy, D; Rappoport, C; Schwarze, S; Collins, S

    2015-04-01

    Determining when to start antiretroviral treatment (ART) is vitally important for people living with HIV. Yet the optimal point at which to start to maximize clinical benefit remains unknown. In the absence of randomized studies, current guidelines rely on conflicting observational data and expert opinion, and consequently diverge on this point. In the USA, ART is recommended irrespective of CD4 cell count. The World Health Organization now recommends starting ART at a CD4 cell count of 500 cells/μL, while the threshold for the UK and South Africa remains at 350 cells/μL. The Strategic Timing of AntiRetroviral Treatment (START) study, one of the largest clinical trials on the treatment of HIV infection, will answer this question. START compares two treatment strategies: immediate treatment at a CD4 cell count of 500 cells/μL or higher versus deferring treatment until the CD4 cell count decreases to 350 cells/μL or until AIDS develops. START includes seven substudies, five of which will clarify the relative contributions of HIV and ART in common comorbidities. START is fully enrolled and expected to be completed in 2016. HIV advocates support the study's design and have been involved from inception to enrolment. The trial will produce rigorous data on the benefits and risks of earlier treatment. It will inform policy and treatment advocacy globally, benefitting the health of HIV-positive people.

  8. Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada

    PubMed Central

    Samji, Hasina; Taha, Taha E; Moore, David; Burchell, Ann N; Cescon, Angela; Cooper, Curtis; Raboud, Janet M; Klein, Marina; Loutfy, Mona R; Machouf, Nima; Tsoukas, Chris M; Montaner, Julio SG; Hogg, Robert S

    2014-01-01

    Background Sustained optimal use of combination antiretroviral treatment (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. Methods cART-naïve individuals ≥18 years of age who initiated cART between 2000–2011 were included. We defined TIs as ≥90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. Results 7,633 participants were eligible, of whom 1,860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women (adjusted hazard ratio (aHR): 1.59, 95%CI: 1.33–1.92), younger individuals (aHR: 1.27, 95%CI: 1.15–1.37 per decade increase), earlier treatment initiators (CD4 count ≥350 versus <200 mm3, aHR: 1.46, 95%CI: 1.17–1.81), Aboriginal participants (aHR: 1.67, 95%CI: 1.27–2.20), injecting drug users (aHR: 1.43, 95%CI: 1.09–1.89), and users of zidovudine versus tenofovir in the initial cART regimen (aHR: 2.47, 95%CI: 1.92–3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 mm3 at cART initiation. Conclusion Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART. PMID:25174373

  9. Guillain Barre syndrome in an HIV-1-infected patient after the beginning of combined antiretroviral therapy: an immune reconstitution inflammatory syndrome?

    PubMed

    Fantauzzi, Alessandra; Digiulio, Maria Anna; Cavallari, Eugenio Nelson; d'Ettorre, Gabriella; Vullo, Vincenzo; Mezzaroma, Ivano

    2014-01-01

    HIV-1-associated Guillan-Barre syndrome (hGBS) is an ascendant progressive polyradiculoneuropathy described throughout the course of the viral disease, mainly associated with the acute retroviral syndrome. HGBS is occasionally described in severely immunocompromised subjects in the context of the immune reconstitution inflammatory syndrome. The case described occurred soon after the start of a combined antiretroviral treatment in an HIV-1 infected patient with ulcerative colitis in the absence of severe immunosuppression. This manifestation may be interpreted as an uncommon appearance of an immune reconstitution syndrome in the presence of a predisposing autoimmune pathology.

  10. Neurocognitive Change in the Era of HIV Combination Antiretroviral Therapy: The Longitudinal CHARTER Study

    PubMed Central

    Heaton, Robert K.; Franklin, Donald R.; Deutsch, Reena; Letendre, Scott; Ellis, Ronald J.; Casaletto, Kaitlin; Marquine, Maria J.; Woods, Steven P.; Vaida, Florin; Atkinson, J. Hampton; Marcotte, Thomas D.; McCutchan, J. Allen; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; Sacktor, Ned; Morgello, Susan; Simpson, David M.; Abramson, Ian; Gamst, Anthony C.; Fennema-Notestine, Christine; Smith, David M.; Grant, Igor; Grant, Igor; McCutchan, J. Allen; Ellis, Ronald J.; Marcotte, Thomas D.; Franklin, Donald; Ellis, Ronald J.; McCutchan, J. Allen; Alexander, Terry; Letendre, Scott; Capparelli, Edmund; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; Dawson, Matthew; Smith, David M.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Marcotte, Thomas D.; Marquie-Beck, Jennifer; McArthur, Justin; Rogalski, Vincent; Morgello, Susan; Simpson, David; Mintz, Letty; McCutchan, J. Allen; Toperoff, Will; Collier, Ann; Marra, Christina; Jones, Trudy; Gelman, Benjamin; Head, Eleanor; Clifford, David; Al-Lozi, Muhammad; Teshome, Mengesha

    2015-01-01

    Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions. PMID:25362201

  11. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    PubMed

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  12. 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

  13. High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

    PubMed Central

    Hasson, Sidgi Syed Anwer; Al-Balushi, Mohammed Saeed; Al Yahmadi, Muzna Hamed; Al-Busaidi, Juma Zaid; Said, Elias Antony; Othman, Mohammed Shafeeq; Sallam, Talal Abdullah; Idris, Mohammed Ahmad; Al-Jabri, Ali Abdullah

    2014-01-01

    Objective To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). Methods A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions. Results The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss. Conclusions ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss. PMID:25183329

  14. Estimating antiretroviral treatment coverage rates and viral suppression rates for homosexual men in Australia

    PubMed Central

    De La Mata, Nicole L.; Mao, Limin; De Wit, John; Smith, Don; Holt, Martin; Prestage, Garrett; Wilson, David P.; Petoumenos, Kathy

    2016-01-01

    Gay and other men who have sex with men (GMSM) are disproportionally affected by the HIV epidemic in Australia. The study objective is to combine a clinical-based cohort with a community-based surveillance system to present a broader representation of the GMSM community to determine estimates of proportions receiving antiretroviral therapy (ART) and/or with an undetectable viral load. Between 2010 and 2012, small increases were shown in ART uptake (to 70.2%) and proportions with undetectable viral load (to 62.4%). The study findings highlight the potential for significantly increasing ART uptake among HIV-positive GMSM to reduce the HIV epidemic in Australia. PMID:26166247

  15. Tuberculosis treatment and risk of stavudine substitution in first line antiretroviral therapy

    PubMed Central

    Westreich, Daniel J.; Sanne, Ian; Maskew, Mhairi; Malope-Kgokong, Babatyi; Conradie, Francesca; Majuba, Pappie; Funk, Michele Jonsson; Kaufman, Jay S.; Van Rie, Annelies; MacPhail, Patrick

    2009-01-01

    Background Treatment for tuberculosis (TB) is common among individuals receiving stavudine-containing highly active antiretroviral therapy (HAART), but the effect of TB treatment on stavudine toxicity has received little attention. We estimated the effect of TB treatment on risk of stavudine substitution among individuals receiving first-line HAART. Methods We evaluated a cohort of 7,066 patients who initiated HAART between April 2004 and March 2007 in Johannesburg, South Africa. Three exposure categories were considered: ongoing TB treatment at HAART initiation; concurrent initiation of TB treatment and HAART; incident TB treatment after HAART initiation. The outcome was single-drug stavudine substitution. Adjusted hazard ratios (aHRs) were estimated using marginal structural models to control for confounding, loss to follow-up, and competing risks. Results Individuals with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dose. For ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI] 1.82-5.56) in the first two months of HAART, 2.51 (95% CI 1.77-3.54) in months 3-6, and 1.19 (95% CI 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95% CI 3.03-14.37) in the first two months,1.88 (95% CI 0.87-4.09) in months 3-6, and 1.07 (95% CI 0.65-1.76) thereafter. There was no effect of incident TB on stavudine substitution risk. Conclusions Risk of stavudine substitution was increased among patients receiving TB treatment, especially soon after HAART initiation. In settings where alternative antiretroviral drugs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered. PMID:19385733

  16. Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection

    PubMed Central

    Lok, Judith J; Bosch, Ronald J; Benson, Constance A; Collier, Ann C; Robbins, Gregory K; Shafer, Robert W; Hughes, Michael D

    2010-01-01

    Objective To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4+ T-cell counts (CD4 counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 count trajectory accounting for losses-to-follow-up and treatment discontinuations. Design The study population included 898 U.S. patients first initiating ART in a randomized trial (ACTG 384); 575 were subsequently prospectively followed in an observational study (ALLRT). Methods Inverse probability of censoring weighting statistical methods were used to estimate the CD4 count trajectory accounting for losses-to-follow-up and ART-discontinuations, overall and for pre-treatment CD4 count categories ≤ 200, 201–350, 351–500, and >500 cells/mm3. Results Median CD4 count increased from 270 cells/mm3 pre-ART to an estimated 556 at three and 532 cells/mm3 at seven years after starting ART in analyses ignoring treatment discontinuations; and to 570 and 640 cells/mm3, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25%, 9%, 3% and 2% of patients with pre-treatment CD4 counts of ≤ 200, 201–350, 351–500, and >500 cells/mm3 would have had CD4 counts ≤350 cells/mm3 after seven years. Conclusions If patients remain on ART, CD4 counts increase in most patients for at least seven years. However, the substantial percentage of patients starting therapy at low CD4 counts who still had low CD4 counts after seven years provides support for ART initiation at higher CD4 counts. PMID:20467286

  17. Active pharmaceutical ingredients for antiretroviral treatment in low- and middle-income countries: a survey.

    PubMed

    Fortunak, Joseph M; de Souza, Rodrigo O M A; Kulkarni, Amol A; King, Christopher L; Ellison, Tiffany; Miranda, Leandro S M

    2014-01-01

    Active pharmaceutical ingredients (APIs) are the molecular entities that exert the therapeutic effects of medicines. This article provides an overview of the major APIs that are entered into antiretroviral therapy (ART), outlines how APIs are manufactured, and examines the regulatory and cost frameworks of manufacturing ART APIs used in low- and middle-income countries (LMICs). Almost all APIs for ART are prepared by chemical synthesis. Roughly 15 APIs account for essentially all of the ARTs used in LMICs. Nearly all of the ART APIs purchased through the Global Fund for AIDS, TB and Malaria (GFATM) or the United States President's Emergency Plan for AIDS Relief (PEPFAR) are produced by generic companies. API costs are very important because they are the largest contribution to the overall cost of ART. Efficient API production requires substantial investment in chemical manufacturing technologies and the ready availability of raw materials and energy at competitive prices. Generic API production is practiced in only a limited number of countries; the API market for ART is dominated by Indian companies. The quality of these APIs is ensured by manufacturing under good manufacturing practice (GMP), including process validation, testing against previously established specifications and the demonstration of clinical bioequivalence. The investment and personnel costs of a quality management system for GMP contribute significantly to the cost of API production. Chinese companies are the major suppliers for many advanced intermediates in API production. Improved chemistry of manufacturing, economies of scale and optimization of procurement have enabled drastic cost reductions for many ART APIs. The available capacity for global production of quality-assured APIs is likely adequate to meet forecasted demand for 2015. The increased use of ART for paediatric treatment, for second-line and salvage therapy, and the introduction of new APIs and combinations are important factors

  18. Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe.

    PubMed

    De Luca, Andrea; Dunn, David; Zazzi, Maurizio; Camacho, Ricardo; Torti, Carlo; Fanti, Iuri; Kaiser, Rolf; Sönnerborg, Anders; Codoñer, Francisco M; Van Laethem, Kristel; Vandamme, Anne-Mieke; Bansi, Loveleen; Ghisetti, Valeria; van de Vijver, David A M C; Asboe, David; Prosperi, Mattia C F; Di Giambenedetto, Simona

    2013-04-15

    HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis.

  19. Antiretroviral treatment in pregnancy: a six-year perspective on recent trends in prescription patterns, viral load suppression, and pregnancy outcomes.

    PubMed

    Baroncelli, Silvia; Tamburrini, Enrica; Ravizza, Marina; Dalzero, Serena; Tibaldi, Cecilia; Ferrazzi, Enrico; Anzidei, Gianfranco; Fiscon, Marta; Alberico, Salvatore; Martinelli, Pasquale; Placido, Giuseppina; Guaraldi, Giovanni; Pinnetti, Carmela; Floridia, Marco

    2009-07-01

    The aim of the study was to describe the recent trends in antiretroviral treatment in late pregnancy and the sociodemographic changes among pregnant women with HIV over the last 6 years. Data from the National Program on Surveillance on Antiretroviral Treatment in Pregnancy in Italy were grouped per calendar year, and changes in antiretroviral treatment, population characteristics, maternal immunovirologic status and newborn clinical parameters were analyzed. A total of 981 HIV-infected mothers who delivered between 2002 and 2008 were evaluated. The proportion of women receiving at least three antiretroviral drugs at delivery increased significantly from 63.0% in 2002 to 95.5% in 2007-2008, paralleled by a similar upward trend in the proportion of women who achieved complete viral suppression at third trimester (from 37.3 in 2002 to 80.9 in 2007-2008; p < 0.001). The co-formulation of zidovudine plus lamivudine remained the most common nucleoside backbone in pregnancy, even if a significant increase in the use of tenofovir plus emtricitabine was observed in more recent years. Starting from 2003, nevirapine prescription declined, paralleled by a significant rise in the use of protease inhibitors (PI), which were present in more than 60% of regimens administered in 2007-2008. Nelfinavir was progressively replaced by ritonavir-boosted PIs, mainly lopinavir. No significant changes in preterm delivery, Apgar score, birth weight, and birth defects were observed during the study period, and the rate of HIV transmission remained below 2%. These data demonstrate a significant evolution in the treatment of HIV in pregnancy. Constant improvements in the rates of HIV suppression were observed, probably driven by the adoption of stronger and more effective regimens and by the increasing options available for combination treatment.

  20. Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions

    PubMed Central

    Seoane, Elena; Resino, Salvador; Moreno, Santiago; de Quiros, Juan Carlos Lopez Bernaldo; Moreno, Ana; Rubio, Rafael; Gonzalez-García, Juan; Arribas, José Ramón; Pulido, Federico; Muñoz-Fernández, Ma Ángeles

    2008-01-01

    Background The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4+ cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions. Methods 27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4+ cell count to < 350/μL. Results After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/μL. Patients with a CD4+ nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to Mycobacterium tuberculosis purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4+ cell count to < 350/μL. Conclusion Both the number (CD4+ nadir) and the functional activity of CD4+ (lymphoproliferative response to PPD) predict the CD4+ decrease associated with discontinuation of ART in patients with controlled viremia. PMID:18302775

  1. [Recommendations for initial antiretroviral treatment in HIV-infected children. Update 2003].

    PubMed

    2004-03-01

    Highly active antiretroviral therapy in HIV-infected children has been associated with a dramatic decrease in progression to AIDS and HIV-related deaths, and infected children currently have an excellent quality of life. Antiretroviral drugs cannot eradicate the virus, although they can achieve a situation of latent infection. However, chronic use of these drugs has multiple adverse effects, the most important of which are metabolic complications. The large number of drugs required and patient characteristics such as age, tolerance to drugs, adherence, and social problems make unifying the criteria for initial therapy in HIV-infected children difficult. A balance should be sought between not delaying the start of treatment, to avoid immunologic deterioration, and minimizing the long-term adverse effects of the therapy. The present treatment recommendations are adapted from international guidelines and are based on a literature review and on our own experience. Our group previously published recommendations on the treatment of HIV-infected children and the aim of the present article is to provide an update.

  2. Mathematical analysis of a two strain HIV/AIDS model with antiretroviral treatment.

    PubMed

    Bhunu, C P; Garira, W; Magombedze, G

    2009-09-01

    A two strain HIV/AIDS model with treatment which allows AIDS patients with sensitive HIV-strain to undergo amelioration is presented as a system of non-linear ordinary differential equations. The disease-free equilibrium is shown to be globally asymptotically stable when the associated epidemic threshold known as the basic reproduction number for the model is less than unity. The centre manifold theory is used to show that the sensitive HIV-strain only and resistant HIV-strain only endemic equilibria are locally asymptotically stable when the associated reproduction numbers are greater than unity. Qualitative analysis of the model including positivity, boundedness and persistence of solutions are presented. The model is numerically analysed to assess the effects of treatment with amelioration on the dynamics of a two strain HIV/AIDS model. Numerical simulations of the model show that the two strains co-exist whenever the reproduction numbers exceed unity. Further, treatment with amelioration may result in an increase in the total number of infective individuals (asymptomatic) but results in a decrease in the number of AIDS patients. Further, analysis of the reproduction numbers show that antiretroviral resistance increases with increase in antiretroviral use.

  3. Therapeutic Immunization In HIV Infected Ugandans Receiving Stable Antiretroviral Treatment: A Phase I Safety Study4

    PubMed Central

    Kityo, Cissy; Bousheri, Stephanie; Akao, Juliette; Ssali, Francis; Byaruhanga, Rose; Ssewanyana, Isaac; Muloma, Prossy; Myalo, Sula; Magala, Rose; Lu, Yichen; Mugyenyi, Peter; Cao, Huyen

    2011-01-01

    Therapeutic immunizations in HIV infection may boost immunity during antiretroviral treatment. We report on the first therapeutic vaccine trial in Uganda, Africa. This open label Phase I trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic HIV-1 vaccine candidate. Thirty HIV positive volunteers receiving a stable regimen of antiretroviral therapy with CD4 counts > 400 were recruited for the safety evaluation of LFn-p24C, a detoxified anthrax-derived polypeptide fused to the subtype C HIV gag protein p24. The vaccine was well tolerated and HIV RNA levels remained undetectable following three immunizations. CD4 counts in vaccine recipients were significantly higher compared to the control individuals after 12 months. HIV-specific responses were associated with higher gain in CD4 counts following LFn-p24C immunizations. Volunteers were subsequently asked to undergo a 30-day period of observed treatment interruption. 8/24 (30%) individuals showed no evidence of viral rebound during treatment interruption. All demonstrated prompt suppression of viral load following resumption of ART. Our data demonstrates the safety of LFn-p24C and suggests that adjunct therapeutic immunization may benefit select individuals in further boosting an immune response. PMID:21211581

  4. Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques.

    PubMed

    Boasso, Adriano; Vaccari, Monica; Fuchs, Dietmar; Hardy, Andrew W; Tsai, Wen-Po; Tryniszewska, Elzbieta; Shearer, Gene M; Franchini, Genoveffa

    2009-04-01

    Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-d-tryptophan (d-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). d-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, d-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, d-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-beta mRNA expression in lymph nodes of ART-treated macaques after d-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by d-1mT, which may account for the lack of effect on plasma Kyn. Finally, d-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, d-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which d-1mT inhibited SIV replication in vivo. PMID:19299731

  5. Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects.

    PubMed

    Palmer, Clovis S; Anzinger, Joshua J; Zhou, Jingling; Gouillou, Maelenn; Landay, Alan; Jaworowski, Anthony; McCune, Joseph M; Crowe, Suzanne M

    2014-12-01

    Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.

  6. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.

  7. Challenges of antiretroviral treatment in transient and drug-using populations: the SUN study.

    PubMed

    Sension, M G; Farthing, C; Shaffer, A G; Graham, E; Siemon-Hryczyk, P; Pilson, R S

    2001-03-01

    This is an open-label, single-arm, phase 3b study (part of phase 3 development) to evaluate the efficacy and safety of Fortovase-soft gelatin formulation (saquinavir-SGC), combined with zidovudine (ZDV) and lamivudine (3TC), human immune deficiency virus type 1 in (HIV-1)-positive, antiretroviral-naive individuals. Forty-two HIV-1-positive adults with plasma HIV RNA >10,000 copies per milliliter (Roche Amplicor HIV Monitor assay) and CD4 cell count >100 cells/mm(3) were treated with SQV-SGC, 1200 mg three times per day; ZDV, 300 mg; and 3TC, 150 mg each twice per day for 48 weeks. High proportions were drug users (26%), demonstrated psychiatric disorders (alcohol abuse [14%]/depression [14%]), or were inadequately housed (5%). At 48 weeks, 50% of patients achieved viral suppression <400 copies per milliliter with 43% <20 copies per milliliter using an intent-to-treat analysis (missing values counted as virological failures). Corresponding proportions for patients remaining on therapy at 48 weeks were 91% <400 copies per milliliter and 78% <20 copies per milliliter. Most adverse events were mild. Saquinavir-SGC combined with ZDV and 3TC, achieved potent and durable HIV RNA suppression and was well tolerated over 48 weeks in an antiretroviral-naive population including high proportions of individuals considered difficult to treat, such as drug users, people with psychiatric problems and homeless individuals. PMID:11313025

  8. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil.

    PubMed

    Lopes, Carmen Andréa F; Soares, Marcelo A; Falci, Diego R; Sprinz, Eduardo

    2015-01-01

    HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

  9. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil.

    PubMed

    Lopes, Carmen Andréa F; Soares, Marcelo A; Falci, Diego R; Sprinz, Eduardo

    2015-01-01

    HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option. PMID:26543866

  10. Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

    PubMed Central

    Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

    2014-01-01

    Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

  11. Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008–2010

    PubMed Central

    Webb Mazinyo, Ernesha; Kim, Lindsay; Masuku, Sikhethiwe; Lancaster, Joey L.; Odendaal, Ronel; Uys, Margot; Podewils, Laura Jean; Van der Walt, Martie L.

    2016-01-01

    Background Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. Methods A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008–31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. Results Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). Conclusions The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment. PMID:27442440

  12. Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa.

    PubMed

    Mekuria, Legese A; Sprangers, Mirjam A G; Prins, Jan M; Yalew, Alemayehu W; Nieuwkerk, Pythia T

    2015-01-01

    Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify patients most in need of additional support and to design appropriate interventions. A cross-sectional study was conducted between September 2012 and April 2013 in 10 healthcare facilities in Addis Ababa, Ethiopia. Patients who were at least 6 months on cART were randomly selected and individual patient data were retrieved from medical records. HRQoL was measured by the WHOQoL-HIVBREF, depressive-symptoms by the Kessler-6 scale, and stigma by the Kalichman internalized AIDS-related stigma scale. Multivariate linear regression analysis was carried-out to examine associations between HRQoL and the other variables. A total of 664 patients (response-rate 95%) participated in the study. A higher level of depressive-symptoms was most strongly and consistently associated with a lower HRQoL, both in terms of the magnitude of the relationship and in the number of HRQoL domains associated with it. Also, a higher level of HIV-stigma was associated with a lower HRQoL except for the physical domain, while obtaining sufficient nutritious food and job opportunity were associated with a better HRQoL except for the spiritual and social domains, respectively. Demographics, clinical, and treatment characteristics yielded few significant associations with HRQoL. Our study findings suggest that interventions to improve HRQoL should focus on reducing depressive-symptoms and HIV-stigma, and on enhancing food security and job opportunity. PMID:25782603

  13. Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

    PubMed

    Ku, Nam Su; Jiamsakul, Awachana; Ng, Oon Tek; Yunihastuti, Evy; Cuong, Do Duy; Lee, Man Po; Sim, Benedict Lim Heng; Phanuphak, Praphan; Wong, Wing-Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Pujari, Sanjay; Chaiwarith, Romanee; Oka, Shinichi; Mustafa, Mahiran; Kumarasamy, Nagalingeswaran; Van Nguyen, Kinh; Ditangco, Rossana; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Durier, Nicolas; Choi, Jun Yong

    2016-08-01

    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.

  14. The association between combination antiretroviral adherence and AIDS-defining conditions at HIV diagnosis.

    PubMed

    Abara, Winston E; Xu, Junjun; Adekeye, Oluwatoyosi A; Rust, George

    2016-08-01

    Combination antiretroviral therapy (cART) has changed the clinical course of HIV. AIDS-defining conditions (ADC) are suggestive of severe or advanced disease and are a leading cause of HIV-related hospitalizations and death among people living with HIV/AIDS (PLWHA) in the USA. Optimal adherence to cART can mitigate the impact of ADC and disease severity on the health and survivability of PLWHA. The objective of this study was to evaluate the association between ADC at HIV diagnosis and optimal adherence among PLWHA. Using data from the 2008 and 2009 Medicaid data from 29 states, we identified individuals, between 18 and 49 years, recently infected with HIV and with a cART prescription. Frequencies and descriptive statistics were conducted to characterize sample. Univariate and multivariable Poisson regression analyses were employed to evaluate the association optimal cART adherence (defined as ≥ 95% study days covered by cART) and ADC at HIV diagnosis (≥1 ADC) were assessed. Approximately 17% of respondents with ADC at HIV diagnosis reported optimal cART adherence. After adjusting for covariates, respondents with an ADC at HIV diagnosis were less likely to report optimal cART adherence (adjusted prevalence ratio (APR) = 0.64, 95% confidence intervals (CI), 0.54-0.75). Among the covariates, males (APR=1.10, 95% CI, 1.02-1.19) compared to females were significantly more likely to report optimal adherence while younger respondents, 18-29 years (APR=0.67, 95% CI, 0.57-0.77), 30-39 years (APR=0.86, 95% CI, 0.79-0.95) compared to older respondents were significantly less likely to report optimal adherence. PLWHA with ADC at HIV diagnosis are at risk of suboptimal cART adherence. Multiple adherence strategies that include healthcare providers, case managers, and peer navigators should be utilized to improve cART adherence and optimize health outcomes among PLWHA with ADC at HIV diagnosis. Targeted adherence programs and services are required to address

  15. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal.

    PubMed

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-03-01

    For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver-child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver-child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information-motivation-behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child's immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment administration by

  16. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-01-01

    ABSTRACT For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver–child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver–child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information–motivation–behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child’s immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment

  17. Can we rely on the antiretroviral treatment as the only means for human immunodeficiency virusprevention? A Public Health perspective.

    PubMed

    Mozalevskis, Antons; Manzanares-Laya, Sandra; García de Olalla, Patricia; Moreno, Antonio; Jacques-Aviñó, Constanza; Caylà, Joan A

    2015-11-01

    The evidence that supports the preventive effect of combination antiretroviral treatment (cART) in HIV sexual transmission suggested the so-called 'treatment as prevention' (TAP) strategy as a promising tool for slowing down HIV transmission. As the messages and attitudes towards condom use in the context of TAP appear to be somehow confusing, the aim here is to assess whether relying on cART alone to prevent HIV transmission can currently be recommended from the Public Health perspective. A review is made of the literature on the effects of TAP strategy on HIV transmission and the epidemiology of other sexual transmitted infections (STIs) in the cART era, and recommendations from Public Health institutions on the TAP as of February 2014. The evolution of HIV and other STIs in Barcelona from 2007 to 2012 has also been analysed. Given that the widespread use of cART has coincided with an increasing incidence of HIV and other STIs, mainly amongst men who have sex with men, a combination and diversified prevention methods should always be considered and recommended in counselling. An informed decision on whether to stop using condoms should only be made by partners within stable couples, and after receiving all the up-to-date information regarding TAP. From the public health perspective, primary prevention should be a priority; therefore relying on cART alone is not a sufficient strategy to prevent new HIV and other STIs.

  18. Misclassification of First–Line Antiretroviral Treatment Failure Based on Immunological Monitoring of HIV Infection in Resource–limited Settings

    PubMed Central

    Kantor, Rami; Diero, Lameck; DeLong, Allison; Kamle, Lydia; Muyonga, Sarah; Mambo, Fidelis; Walumbe, Eunice; Emonyi, Wilfred; Chan, Philip; Carter, E. Jane; Hogan, Joseph; Buziba, Nathan

    2016-01-01

    Background The monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity, mortality, and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. Methods Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing immunological failure (ie, their CD4 cell count decreased by ⩾25% in 6 months). Misclassification of treatment failure was defined as a ⩾25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cell percentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease). Results There were 149 patients who were treated for 23 months; they were identified as having a ⩾25% decrease in CD4 cell count (from 375 to 216 cells/μL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients, 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a ⩾50% decrease in CD4 cell count, 18 (43%) were misclassified. In multivariate logistic regression, misclassification odds were associated with a higher CD4 cell count, a shorter duration of therapy, and a smaller CD4% percent decrease. By combining these variables, we may be able to improve our ability to predict treatment failure. Conclusions Immunological monitoring as a sole indicator of virological failure would lead to a premature switch to

  19. Prevention of HIV-1 Infection with Early Antiretroviral Therapy: Treatment as -

    NASA Astrophysics Data System (ADS)

    Gilada, Ishwar; Gilada, T.

    2014-07-01

    There are 34.2 million living with HIV/AIDS globally according to the UNAIDS. The incidence is 2.5 million new infections every year. Out of the 24.8 million patients eligible for antiretroviral treatment, only 8 million are actually receiving it. Nearly 1.7 million people (4658 per day) die of the disease every year i.e., 4658/day, making HIV/AIDS a planetary emergency. The most disturbing fact is that more than 50% of the infected people do not reveal their HIV status to their sexual partners. The UN Sec-Gen Ban Ki-moon suggested "3 Zeros"--Zero Infection, Zero Stigma, Zero AIDS-deaths in 2008...

  20. Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

    PubMed

    Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

    2016-03-01

    The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding.

  1. Patterns of geographic mobility predict barriers to engagement in HIV care and antiretroviral treatment adherence.

    PubMed

    Taylor, Barbara S; Reyes, Emily; Levine, Elizabeth A; Khan, Shah Z; Garduño, L Sergio; Donastorg, Yeycy; Hammer, Scott M; Brudney, Karen; Hirsch, Jennifer S

    2014-06-01

    Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

  2. Patterns of Geographic Mobility Predict Barriers to Engagement in HIV Care and Antiretroviral Treatment Adherence

    PubMed Central

    Reyes, Emily; Levine, Elizabeth A.; Khan, Shah Z.; Garduño, L. Sergio; Donastorg, Yeycy; Hammer, Scott M.; Brudney, Karen; Hirsch, Jennifer S.

    2014-01-01

    Abstract Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

  3. Antiretroviral treatment adherence in childhood and adolescence: multidisciplinary team as an associated factor in Brazil.

    PubMed

    Crozatti, Marcia Terezinha Lonardoni; França-Junior, Ivan; Rodrigues, Rosangela; Carneiro Ferrão, Maria do Socorro; Brigido, Luis Fernando M; Della Negra, Marinella; Campéas, Alexandre Ely; Castilho Raymundo, Miriam Elia; Marques, Silvia Regina; Waldman, Eliseu Alves

    2013-01-01

    Our aim was to analyze factors associated with non-adherence to antiretroviral (ARV) treatment among children and adolescents. A cross-sectional study was carried out involving non-institutionalized children and adolescents between 2 and 20 years of age, addressing non-adherence to ARV treatment, which was defined as taking ≤89% of the medications on the day of the interview and the three previous days. The investigation into the association between non-compliance and the variables of interest was performed using unconditional logistic regression. The independent factors associated with non-adherence were forgetfulness (OR = 3.22; 95%CI = 1.75-5.92), difficulties coping with treatment (OR = 2.65; 95%CI = 1.03-6.79), and living with grandparents (OR = 2.28; 95%CI = 1.08-4.83), whereas a protective effect was found with participation in multidisciplinary activities (OR = 0.49; 95%CI = 0.25-0.96), i.e., this factor indicates that the exposure to the variable is beneficial, promoting adherence. We concluded that forgetting to take the medications and reporting having difficulty coping with ARV treatment are potentially modifiable factors through educational and programmatic actions. Residing with one's grandparents may strongly impact adherence to ARV treatment, indicating the need for the systematic support of these family members. Participation in multidisciplinary activities should be stimulated at health-care services.

  4. Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar

    PubMed Central

    Shewade, H. D.; Kyaw, N. T. T.; Oo, M. M.; Aung, T. K.; Aung, S. T.; Oo, H. N.; Win, T.; Harries, A. D.

    2016-01-01

    Setting: Integrated HIV Care programme, Mandalay, Myanmar. Objectives: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. Design: Retrospective cohort study. Results: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm3 had a four times higher risk of an unsuccessful outcome. Conclusions: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV. PMID:27358804

  5. Impact of three empirical tuberculosis treatment strategies for people initiating antiretroviral therapy

    PubMed Central

    Van Rie, Annelies; Westreich, Daniel; Sanne, Ian

    2016-01-01

    Background Early mortality in people initiating antiretroviral treatment (ART) in Africa remains high. Empiric TB treatment strategies aim to reduce early mortality by initiating TB treatment in individuals without clinical suspicion of TB who are at high-risk of death from undiagnosed TB. Methods Using data from 16,913 individuals starting ART under programmatic conditions, we simulated the impact of three empiric treatment strategies on mortality and incident TB: two randomized clinical trials (REMEMBER and PrOMPT) and a pragmatic approach. The main analysis assumed that 50% of early deaths and 100% of incident TB is averted in those eligible and ignored outcomes in those lost to follow up. Results The increase in individuals eligible for TB treatment under empirical TB treatment strategies ranged from 4.4% to 31.4% as compared to those started on clinical or mycobacteriological grounds. The proportion of deaths averted by empiric treatment strategies ranged from 5.5% to 25.4%. The proportion of incident TB cases averted ranged from 10.9% to 57.3%. The proportion receiving any TB treatment during the first six months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% and 51.3% under the PrOMPT, REMEMBER and pragmatic approach, respectively. Conclusion The impact of empiric TB treatment strategies depends greatly on the eligibility criteria chosen. The additional strain placed on TB treatment facilities and the relatively limited impact of some empirical TB strategies raise the question whether the benefits will outweigh the risks at population level. PMID:25299868

  6. 12 Weeks of Daclatasvir in Combination With Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens

    PubMed Central

    Luetkemeyer, Anne F.; McDonald, Cheryl; Ramgopal, Moti; Noviello, Stephanie; Bhore, Rafia; Ackerman, Peter

    2016-01-01

    Background. Highly effective hepatitis C virus (HCV) direct-acting antiviral therapies that do not require modification of human immunodeficiency virus (HIV) antiretroviral regimens are needed. We evaluated the efficacy and safety of daclatasvir + sofosbuvir (DCV + SOF) for 12 weeks by antiretroviral (ARV) regimen in HIV-HCV-coinfected patients. Methods. In the randomized, open-label ALLY-2 study, HIV-HCV-coinfected patients received 8 or 12 weeks of once-daily DCV 60 mg (dose-adjusted as-necessary for concomitant ARVs) + SOF 400 mg. Results were stratified by ARV class for the 151 patients who received 12 weeks of DCV + SOF. Results. Fifty-one patients were HCV treatment experienced, 100 were treatment naive, 89% male and 33% black. HCV genotypes were: genotype 1a (GT1a; 69%), GT1b (15%), GT2 (8%), GT3 (6%), and GT4 (2%). Sustained virologic response 12 weeks post-treatment (SVR12) was 97% and was similar across ARV regimens (P = .774): protease inhibitor-based, 97% (95% confidence interval [CI], 90%-99.7%); nonnucleoside reverse transcriptase inhibitor-based, 100% (95% CI, 91%-100%); and integrase inhibitor based, 95% (95% CI, 83%-99.4%). SVR12 among patients receiving either tenofovir disoproxil fumarate or abacavir as part of their antiretroviral therapy regimen was 98% (95% CI, 93%-99.5%) and 100% (95% CI, 85%-100%), respectively. Age, gender, race, cirrhosis, HCV treatment history, GT , and baseline HCV RNA did not affect SVR12. No discontinuations were attributed to treatment-related adverse events. Conclusions. DCV + SOF x12 weeks is a highly efficacious, all-oral, pan-GT HCV treatment for HIV-HCV coinfected patients across a broad range of ARV regimens. Clinical Trials Registration. NCT02032888. PMID:27025835

  7. Sources of motivation and frustration among healthcare workers administering antiretroviral treatment for HIV in rural Zimbabwe

    PubMed Central

    Campbell, C.; Scott, K.; Madenhire, C.; Nyamukapa, C.; Gregson, S.

    2012-01-01

    The roll-out of accessible and affordable antiretroviral (ARV) drugs for people living with HIV in low-income countries is drastically changing the nature of HIV-related healthcare. The Zimbabwean Ministry of Health has renewed efforts to make antiretroviral treatment (ART) for HIV free and publically available across the country. This paper describes the findings from a multi-method qualitative study including interviews and a focus group with healthcare workers (mostly nurses), totalling 25 participants, and field notes from over 100 hours of ethnographic observation in three rural Zimbabwean health centres. These health centres began providing free ARV drugs to HIV-positive people over one year prior to the research period. We examined sources of motivation and frustration among nurses administering ART in these resource-poor health centres. The findings suggest that healthcare workers administering ART in challenging circumstances are adept at drawing strength from the dramatic physical and emotional recoveries made possible by ART and from their personal memories of the suffering caused by HIV/AIDS among close friends or family. However, healthcare staff grappled with extreme resource shortages, which led to exhaustion and frustration. Surprisingly, only one year into ART provision, healthcare workers did not reference the professional challenges of their HIV work before ART became available, suggesting that medical breakthroughs such as ART rapidly come to be seen as a standard element of nursing. Our findings provide a basis for optimism that medical breakthroughs such as ART can reinvigorate healthcare workers in the short term. However, we caution that the daily challenges of nursing in poor environments, especially administering an ongoing and resource-intensive regime such as ART, must be addressed to enable nurses to continue delivering high-quality ART in sub-Saharan Africa. PMID:21400319

  8. No Differences of Immune Activation and Microbial Translocation Among HIV-infected Children Receiving Combined Antiretroviral Therapy or Protease Inhibitor Monotherapy

    PubMed Central

    Falcon-Neyra, Lola; Benmarzouk-Hidalgo, Omar J.; Madrid, Lola; Noguera-Julian, Antoni; Fortuny, Claudia; Neth, Olaf; López-Cortés, Luis

    2015-01-01

    Abstract This is a cross-sectional study of 15 aviremic chronic HIV-infected children revealing no differences in immune activation (IA; HLA-DR+CD38+ CD4+ and CD8+ T cells, and sCD14) and microbial translocation (MT; lipopolysaccharides (LPS) and 16S rDNA) among HIV-infected patients under combined antiretroviral treatment (cART; n = 10) or ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv; n = 5). In both cases, IA and MT were lower in healthy control children (n = 32). This observational study suggests that ritonavir boosted protease inhibitor monotherapy (mtPI/rtv) is not associated with an increased state of IA or MT as compared with children receiving cART. PMID:25789946

  9. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

    PubMed Central

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  10. Trends and economic stress: a challenge to universal access to antiretroviral treatment in India.

    PubMed

    Dhamija, P; Bansal, D; Medhi, B

    2009-07-01

    The prospects for expanded access to antiretroviral therapy (ART) in resource-poor settings have greatly improved as a result of global and national efforts to reduce the cost of antiretroviral drugs (ARV), growing availability of cheaper generics, and increased financing available from the Global Funds like Medicines Sans Frontieres. Indian health set-up provides drugs free-of-cost to HIV infected patients through government network and also through open-market to those who intend to have personalized care. Post-2005, implementation of WTO agreement on TRIPS is expected to have a significant impact on pricing and availability of generic ARV. The study has been planned to explore the trends and gaps in availability & accessibility of ARV in India. The trends in per-patient-per-year (PPPY) cost of individual ARV and treatment regimes were also explored. The epidemiological data demonstrated stabilization of the epidemic in India. Most ARV are available in India by the generic manufacturers with a median drug lag period of 2.05 years (Range 0.75-6.51 years). There is a significant price difference in drugs available from generic and originator companies. Prices for patented and generic ARV in India reflect price negotiations that have taken place since the introduction of drugs in the country, still most of the ARVs are available at a much higher cost in the market [median 2.6 times (range 1-7)]. The per-patient per year (PPPY) cost of providing first-line regime in 2008 has decreased 2.75 times from that in 2003. The analysis shows the stabilization of prices of all drugs after 2006. HIV spending in India has seen a growth of 26 percent and 28 percent in 2005-06 and 2006-07 respectively. Still, the expected expenditure to cover the whole patient population needing therapy is considerably higher than the actual expenditure incurred for providing ARV. Despite the price reductions and availability of ARV at a lower cost through agencies like MSF, there is a large gap

  11. Does Once-Daily Raltegravir Have Any Role in the Antiretroviral Treatment?

    PubMed Central

    Gutierrez-Valencia, Alicia; Chacón-Mora, Natalia; Ruiz-Valderas, Rosa; Ben-Marzouk-Hidalgo, Omar J.; Torres-Cornejo, Almudena; Viciana, Pompeyo; Lopez-Cortes, Luis F.

    2015-01-01

    Abstract Administering raltegravir once daily would make adherence to antiretroviral treatment easier, especially if the concomitant drugs are also administered once daily. We report our experience on the use of raltegravir, both once- and twice-daily. Retrospective review of HIV-infected patients on treatment with raltegravir 800 mg once or 400 mg twice a day plus 2 analogs. Patients were classified as group A (subjects switched to raltegravir due to adverse events on a previous regimen or drug–drug interactions) and group B (subjects who restarted antiretroviral treatment after a previous drop-out). The primary clinical endpoint was the percentage of subjects with virological suppression after 96 weeks. Treatment's effectiveness (noncomplete/missing equals failure) was also evaluated. Pharmacokinetic study was performed in unselected patients. Plasma raltegravir concentrations were determined by high-performance liquid chromatography coupled with mass spectrometry. A total of 133 patients were included in the study (74 and 59 on raltegravir once- and twice-daily). There were only 4 virological failures in the entire cohort during the follow-up. Thus, the Kaplan–Meier estimation of efficacy by on-treatment analysis was 96.3% (CI95, 92.8–99.8) at week 96, independently of the dosing regimen and of the raltegravir concentrations. Similar exposures to raltegravir based on AUC0–τ, but higher Cmax and significantly lower Ctrough were observed when raltegravir was given once daily compared with 400 mg twice daily. In fact, 14 out of 56 Ctrough concentrations (25%) from patients taking raltegravir once daily were below the IC95 of wild-type HIV-1 clinical isolates while only 2 samples from patients receiving 400 mg twice a day were below this value, although no relationship between Ctrough and efficacy was found. The main limitations of the study are that the raltegravir dosing regimen was not randomized and more than 50% of the patients were

  12. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    PubMed

    Ramiro, Miguel A; Llibre, Josep M

    2014-11-01

    The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation. PMID:24139337

  13. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    PubMed

    Ramiro, Miguel A; Llibre, Josep M

    2014-11-01

    The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation.

  14. Association between risk behaviors and antiretroviral resistance in HIV-infected patients receiving opioid agonist treatment

    PubMed Central

    Tetrault, Jeanette M.; Kozal, Michael J.; Chiarella, Jennifer; Sullivan, Lynn E.; Dinh, An T; Fiellin, David A.

    2013-01-01

    Objectives Antiretroviral (ARV) resistance is of concern. Opioid agonist treatment ( i.e., methadone or buprenorphine) is effective and decreases HIV transmission risk behaviors and HIV seroconversion. Despite prevention efforts, injection drug use (IDU) and risky sexual behaviors remain prevalent in patients receiving opioid agonist treatment. The purpose of this study is to determine in HIV-infected patients receiving opioid agonist treatment, the prevalence of HIV transmission risk behaviors, the prevalence of ARV resistance, and the prevalence of ARV resistance among those with risk behaviors. Methods The design was a cross-sectional, study of patients recruited from opioid treatment programs and outpatient practices. We measured demographic, drug treatment, and HIV clinical information (including ARV adherence), self-reported HIV risk behaviors and drug use, urine toxicologies, and genotype testing for ARV resistance (with both standard assays and Ultradeep sequencing). Data analysis included descriptive statistics. Results 59 subjects enrolled. 64% were male, 24% were white, and mean age was 46 years. 53% were receiving methadone and 47% buprenorphine. 80% were on opioid agonist treatment for 12 weeks or more. 14% reported unprotected sex, 7% reported sharing needles or works, and 60% had positive urine toxicology for illicit drug use. 15% had evidence of HIV resistance by standard genotyping, 7% with single class resistance, 3% with double class resistance, and 5% with triple class resistance. Ultradeep sequencing found additional class resistance in 5 subjects. 22% of subjects with evidence of transmission risk behaviors vs. 14% of subjects without risk behaviors had evidence of ARV resistance. Conclusions Improved prevention and treatment efforts may be needed for HIV-infected, opioid dependent individuals receiving opioid agonist treatment to decrease transmission of ARV resistant virus, especially in resource limited settings. PMID:23388678

  15. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

    PubMed Central

    Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

    2012-01-01

    Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/μL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ μL (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot

  16. Correlates of Unstructured Antiretroviral Treatment Interruption in a Cohort of HIV-Positive Individuals in British Columbia

    PubMed Central

    Samji, Hasina; Chen, Yalin; Salters, Kate; Montaner, Julio S. G.; Hogg, Robert S.

    2014-01-01

    Treatment interruptions (TIs) limit the therapeutic success of combination antiretroviral therapy and are associated with higher morbidity and mortality. HIV-positive individuals dealing with concurrent health issues, access challenges and competing life demands are hypothesized to be more likely to interrupt treatment. Individuals were included if they initiated cART ≥1 year prior to interview date and had a CD4 cell count or initial regimen recorded at initiation. Using pharmacy recording, TIs were defined as a patient-initiated interruption in treatment ≥90 consecutive days during the 12 months preceding or following the study interview. 117 (15%) of 768 participants included in this study had a TI during the study window. 76.0% of participants were male, 27.5% were of Aboriginal ethnicity and the median age was 46 (interquartile range (IQR): 40–52). In multivariable logistic regression, TIs were significantly associated with current illicit drug use (adjusted odds ratio [aOR]: 1.68, 95% confidence interval [CI]: 1.05–2.68); <95% adherence in the first year of treatment (aOR: 2.68, 95% CI: 1.67–4.12); living with more than one person (aOR: 1.95; 95% CI: 1.22–3.14) or living on the street (aOR: 5.08, 95% CI: 1.72–14.99) compared to living alone; poor perception of overall health (aOR: 1.64 95% CI: 1.05–2.55); being unemployed (aOR: 2.22, 95% CI: 1.16–4.23); and younger age at interview (aOR: 0.57, 95% CI: 0.44–0.75, per 10 year increment). Addressing socioeconomic barriers to treatment retention is vital for supporting the continuous engagement of patients in care. PMID:24781638

  17. Allocating scarce financial resources for HIV treatment: benchmarking prices of antiretroviral medicines in Latin America.

    PubMed

    Wirtz, Veronika J; Santa-Ana-Tellez, Yared; Trout, Clinton H; Kaplan, Warren A

    2012-12-01

    Public sector price analyses of antiretroviral (ARV) medicines can provide relevant information to detect ARV procurement procedures that do not obtain competitive market prices. Price benchmarks provide a useful tool for programme managers and policy makers to support such planning and policy measures. The aim of the study was to develop regional and global price benchmarks which can be used to analyse public-sector price variability of ARVs in low- and middle-income countries using the procurement prices of Latin America and the Caribbean (LAC) countries in 2008 as an example. We used the Global Price Reporting Mechanism (GPRM) data base, provided by the World Health Organization (WHO), for 13 LAC countries' ARV procurements to analyse the procurement prices of four first-line and three second-line ARV combinations in 2008. First, a cross-sectional analysis was conducted to compare ARV combination prices. Second, four different price 'benchmarks' were created and we estimated the additional number of patients who could have been treated in each country if the ARV combinations studied were purchased at the various reference ('benchmark') prices. Large price variations exist for first- and second-line ARV combinations between countries in the LAC region. Most countries in the LAC region could be treating between 1.17 and 3.8 times more patients if procurement prices were closer to the lowest regional generic price. For all second-line combinations, a price closer to the lowest regional innovator prices or to the global median transaction price for lower-middle-income countries would also result in treating up to nearly five times more patients. Some rational allocation of financial resources due, in part, to price benchmarking and careful planning by policy makers and programme managers can assist a country in negotiating lower ARV procurement prices and should form part of a sustainable procurement policy. PMID:22367770

  18. Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy

    PubMed Central

    Ku, Nam Su; Jiamsakul, Awachana; Ng, Oon Tek; Yunihastuti, Evy; Cuong, Do Duy; Lee, Man Po; Sim, Benedict Lim Heng; Phanuphak, Praphan; Wong, Wing-Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Pujari, Sanjay; Chaiwarith, Romanee; Oka, Shinichi; Mustafa, Mahiran; Kumarasamy, Nagalingeswaran; Van Nguyen, Kinh; Ditangco, Rossana; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Durier, Nicolas; Choi, Jun Yong

    2016-01-01

    Abstract Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort. We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site. In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14–1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420). This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART. PMID:27512885

  19. HIV Status Disclosure Among People Living with HIV in the Era of Combination Antiretroviral Therapy (cART)

    PubMed Central

    Madi, Deepak; Gupta, Parul; Bhaskaran, Unnikrishnan; Ramapuram, John T.; Rao, Satish; Mahalingam, Soundarya

    2015-01-01

    Introduction As patients with HIV live longer due to Combination Anti-Retroviral Therapy (cART) serostatus disclosure becomes an important issue. Disclosure can have both positive and negative outcomes. Disclosure of HIV status has been associated with better adherence to medication and reduction in levels of psychological distress. Stigma and disruption of family relationships are barriers for disclosure. Most studies regarding disclosure status have been conducted in West. There are many cultural differences in Indian society when compared to west. There is a dearth of research in the field of disclosure of HIV infection in India. Aim To determine the prevalence of HIV status disclosure among people living with HIV (PLHIV) in South India. Materials and Methods This descriptive cross-sectional study was done in the hospital attached to Kasturba Medical College (KMC), Mangalore, India from May–June 2013. PLHIV of age more than 18 years were included. During the study period 111 consecutive patients who consented for the study were enrolled. Statistical Analysis Data was collected using a pre-tested interviewer administered semi structured questionnaire. Data collected was analysed using SPSS Version 11.5 statistical software. Descriptive statistics were done and the results are presented as proportions and mean. Results The mean age of the study population was 44.86 ± 10.8 years. Majority of the study subjects were men 76 (68.4%). Out of 111 study subjects, 102 (91.9%) had disclosed their HIV status to at least one person while 9 (8.1%) had not disclosed their HIV status to anyone. Disclosure on doctor’s advice was the main reason for 56 (54.9%) participants to disclose their HIV status. The main reason for non-disclosure was fear of shame in family. Conclusion Disclosure rate was high in our study in the era of cART. Society must stop discriminating against PLHIV so that they can disclose their serostatus and gain access to care and treatment services without

  20. Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

    PubMed

    Ku, Nam Su; Jiamsakul, Awachana; Ng, Oon Tek; Yunihastuti, Evy; Cuong, Do Duy; Lee, Man Po; Sim, Benedict Lim Heng; Phanuphak, Praphan; Wong, Wing-Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Pujari, Sanjay; Chaiwarith, Romanee; Oka, Shinichi; Mustafa, Mahiran; Kumarasamy, Nagalingeswaran; Van Nguyen, Kinh; Ditangco, Rossana; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Durier, Nicolas; Choi, Jun Yong

    2016-08-01

    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART. PMID:27512885

  1. Current Scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy

    PubMed Central

    Usman, Muhammad; Kandi, Venkataramana

    2016-01-01

    The discovery of the human immunodeficiency virus (HIV) as the causative organism of acquired immunodeficiency syndrome (AIDS) and the inability of modern medicine to find a cure for it has placed HIV as one of the most dreaded pathogens of the 21st century. With millions of people infected with HIV, it was once thought to result in “medical apocalypse”. However, with the advent of antiretroviral therapy (ART), it is now possible to control HIV. Adherence to ART helps to keep the viral load under control and prolong the time of progression to AIDS, resulting in near normal life expectancy. Even with the introduction of ART, a substantial number of patients fail to adhere due to a variety of reasons, including adverse side effects, drug abuse, mental disorders, socioeconomic status, literacy, and social stigma. With the availability of so many options for HIV treatment at each stage of the disease progression, physicians can switch between the treatment regimens to avoid and/or minimize the adverse effects of drugs. Close monitoring, major social reforms, and adequate counselling should also be implemented to circumvent other challenges. PMID:27054050

  2. In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

    PubMed Central

    Scott, K.; Campbell, C.; Madanhire, C.; Skovdal, M.; Nyamukapa, C.; Gregson, S.

    2014-01-01

    Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital. PMID:23503291

  3. Crack cocaine use and adherence to antiretroviral treatment among HIV-infected black women.

    PubMed

    Sharpe, Tanya Telfair; Lee, Lisa M; Nakashima, Allyn K; Elam-Evans, Laurie D; Fleming, Patricia L

    2004-04-01

    Since the appearance of crack cocaine in the 1980s, unprecedented numbers of women have become addicted. A disproportionate number of female crack users are Black and poor. We analyzed interview data of HIV-infected women > or = 18 years of age reported to 12 health departments between July 1997 and December 2000 to ascertain if Black women reported crack use more than other HIV-infected women and to examine the relationship between crack use and antiretroviral treatment (ART) adherence among Black women. Of 1655 HIV-infected women, 585 (35%) were nonusers of drugs, 694 (42%) were users of other drugs and 376 (23%) were crack users. Of the 1196 (72%) Black women, 306 (26%) were crack users. We used logistic regression to examine the effect of crack use on adherence to ART, controlling for age and education among Black women. In multivariate analysis, crack users and users of other drugs were less likely than non-users to take their ART medicines exactly as prescribed (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.24-0.56), OR = 0.47; 95% CI = 0.36-0.68), respectively. HIV-infected Black women substance users, especially crack cocaine users, may require sustained treatment and counseling to help them reduce substance use and adhere to ART.

  4. Current Scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy.

    PubMed

    Bhatti, Adnan Bashir; Usman, Muhammad; Kandi, Venkataramana

    2016-01-01

    The discovery of the human immunodeficiency virus (HIV) as the causative organism of acquired immunodeficiency syndrome (AIDS) and the inability of modern medicine to find a cure for it has placed HIV as one of the most dreaded pathogens of the 21(st) century. With millions of people infected with HIV, it was once thought to result in "medical apocalypse". However, with the advent of antiretroviral therapy (ART), it is now possible to control HIV. Adherence to ART helps to keep the viral load under control and prolong the time of progression to AIDS, resulting in near normal life expectancy. Even with the introduction of ART, a substantial number of patients fail to adhere due to a variety of reasons, including adverse side effects, drug abuse, mental disorders, socioeconomic status, literacy, and social stigma. With the availability of so many options for HIV treatment at each stage of the disease progression, physicians can switch between the treatment regimens to avoid and/or minimize the adverse effects of drugs. Close monitoring, major social reforms, and adequate counselling should also be implemented to circumvent other challenges. PMID:27054050

  5. Barriers and facilitators to patients' adherence to antiretroviral treatment in Zambia: a qualitative study.

    PubMed

    Sanjobo, Nawa; Frich, Jan C; Fretheim, Atle

    2008-09-01

    Patients' adherence to antiretroviral therapy (ART) is important for effective medical treatment of HIV/AIDS. We conducted a qualitative interview study in the Copperbelt Province of Zambia in 2006. The aim of the study was to explore patients' and health care professionals' perceived barriers and facilitators to patients' adherence to ART. Based on data from individual interviews and focus group interviews with a total of 60 patients and 12 health care professionals, we identified barriers and facilitators related to patients' beliefs and behaviours, the health service, and socio-economic and cultural factors. Among the barriers we identified were lack of communication and information about ART, inadequate time during consultations, lack of follow-up and counselling, forgetfulness, stigma, discrimination and disclosure of HIV status, lack of confidentiality in the treatment centres, and lack of nutritional support. Feeling better, prospects of living longer, family support, information about ART, support for income-generating activities, disclosure of HIV status, prayers and transport support were among the facilitators. Our study suggests that several issues need to be considered when providing ART. Further research is needed to study interactions between patients and their health care providers. Our findings can inform interventions to improve adherence to ART.

  6. In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

    PubMed

    Scott, K; Campbell, C; Madanhire, C; Skovdal, M; Nyamukapa, C; Gregson, S

    2014-12-01

    Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital.

  7. Factors Influencing Adherence to Antiretroviral Treatment in Nepal: A Mixed-Methods Study

    PubMed Central

    Wasti, Sharada P.; Simkhada, Padam; Randall, Julian; Freeman, Jennifer V.; van Teijlingen, Edwin

    2012-01-01

    Background Antiretroviral therapy (ART) is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. Methods A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth interviews with three different types of stakeholders: patients, care providers, and key people at policy level. Adherence was assessed through survey self-reporting and during the interviews. A multivariate logistic regression model was used to identify factors associated with adherence, supplemented with a thematic analysis of the interview transcripts. Results A total of 282 (85.5%) respondents reported complete adherence, i.e. no missed doses in the four-weeks prior to interview. Major factors influencing adherence were: non-disclosure of HIV status (OR = 17.99, p =  0.014); alcohol use (OR = 12.89, p = <0.001), being female (OR = 6.91, p = 0.001), being illiterate (OR = 4.58, p = 0.015), side-effects (OR = 6.04, p = 0.025), ART started ≤24 months (OR = 3.18, p = 0.009), travel time to hospital >1 hour (OR = 2.84, p = 0.035). Similarly, lack of knowledge and negative perception towards ART medications also significantly affected non-adherence. Transport costs (for repeat prescription), followed by pills running out, not wanting others to notice, side-effects, and being busy were the most common reasons for non-adherence. The interviews also revealed religious or ritual obstacles, stigma and discrimination, ART-associated costs, transport problems, lack of support, and side-effects as contributing to non-adherence. Conclusion Improving adherence requires a supportive environment; accessible treatment; clear

  8. Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study

    PubMed Central

    Christopoulos, Katerina A.; Olender, Susan; Lopez, Andrea M.; Lekas, Helen-Maria; Jaiswal, Jessica; Mellman, Will; Geng, Elvin; Koester, Kimberly A.

    2015-01-01

    Background Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART. Methods and Findings We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic

  9. [HIV-AIDS medicine, antiretroviral treatment, adherence: a discussion about self-care].

    PubMed

    Margulies, Susana

    2012-01-01

    We propose a reflection on the role of biomedical and clinical action in the organization, promotion and legitimating of discourses and practices of self-care and control in the experience of HIV-AIDS disease. We analyze the conditions and requirements of the so-called "adherence" to antiretroviral treatment, which is of central importance in medical and health actions. Since medical intervention tends to associate viral progression to patient adherence, the "meeting of requirements" implies not only the certainty about medical indication but the very possibility of salvation. Through corporeal monitoring and the control of the interactions and practices of those affected, this medicalizing process directs their behavior, sets forms of discipline and imposes a responsible way to care for themselves. Thus, the power of biomedical institution is not only its ability to define a physical condition through diagnosis but also helps to establish the parameters of illness experience, reconfiguring the ways in which subjects understand and relate to themselves and others, producing new forms of identity, belongings and social relations.

  10. Increasing Antiretroviral Adherence for HIV-Positive African Americans (Project Rise): A Treatment Education Intervention Protocol

    PubMed Central

    Bogart, Laura M; Mutchler, Matt G; McDavitt, Bryce; Mutepfa, Kieta D; Risley, Brian

    2016-01-01

    Background HIV-positive African Americans have been shown to have lower adherence to antiretroviral therapy (ART) than those of other races/ethnicities, yet adherence interventions have rarely been tailored to the needs of this population. Objective We developed and will evaluate a treatment education adherence intervention (called Rise) that was culturally adapted to address the needs of African Americans living with HIV. Methods This randomized controlled trial will examine the effects of the Rise intervention on ART adherence and HIV viral load. African Americans on ART who report adherence problems will be recruited from the community and randomly assigned to receive the intervention or usual care for 6 months. The intervention consists of 6-10 individual counseling sessions, with more sessions provided to those who demonstrate lower adherence. Primary outcomes include adherence as monitored continuously with Medication Event Monitoring Systems (MEMS) caps, and viral load data received from the participant’s medical provider. Survey assessments will be administered at baseline and month 6. Results The trial is ongoing. Conclusions If effective, the Rise intervention will provide community-based organizations with an intervention tailored to address the needs of African Americans for promoting optimal ART adherence and HIV clinical outcomes. Trial Registration Clinicaltrials.gov NCT01350544; https://clinicaltrials.gov/ct2/show/NCT01350544 (Archived by WebCite at http://www.webcitation.org/6fjqqnmn0). PMID:27025399

  11. Rates and Factors Associated with Major Modifications to First-Line Combination Antiretroviral Therapy: Results from the Asia-Pacific Region

    PubMed Central

    Wright, Stephen; Boyd, Mark A.; Yunihastuti, Evy; Law, Matthew; Sirisanthana, Thira; Hoy, Jennifer; Pujari, Sanjay; Lee, Man Po; Petoumenos, Kathy

    2013-01-01

    Background In the Asia-Pacific region many countries have adopted the WHO’s public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region. Methods We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country’s per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class. Results A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44–0.52), 0.33 (0.30–0.36) and 0.21 (0.18–0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. Conclusions Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries

  12. Barriers to Free Antiretroviral Treatment Access for Female Sex Workers in Chennai, India

    PubMed Central

    Chakrapani, Venkatesan; Newman, Peter A.; Shunmugam, Murali; Kurian, Abraham K.

    2009-01-01

    Abstract India's National AIDS Control Organization (NACO) provides free first-line antiretroviral treatment (ART) at government centers for people living with HIV. To assist in developing policies and programs to ensure equity in ART access, we explored barriers to ART access among female sex workers (FSWs) living with HIV in Chennai. Between August and November 2007, we conducted three focus group discussions and two key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family/social, health care system/programmatic, and individual levels. Major barriers included fear of adverse consequences of disclosure of HIV status due to stigma and discrimination associated with HIV and sex work, lack of family support, negative experiences with health care providers, lack of adequate counseling services at government centers and by outreach workers employed by nongovernmental organizations (NGOs), perceived biased treatment of FSWs who are not referred by NGOs, lack of adequate knowledge about ART, and fatalism. Barriers can be addressed by: creating effective measures to reduce stigma associated with HIV/AIDS and sex work at the familial, societal, and health care system levels; incorporating information about ART into targeted interventions among FSWs; training counselors at government hospitals and NGO outreach workers on treatment issues; improving infrastructure and staffing levels at government centers to allow adequate time and privacy for counseling; and implementing government mass media campaigns on ART availability. Finally, it is crucial that NACO begin monitoring ART coverage of FSWs and other marginalized populations to ensure equitable ART access. PMID:19821725

  13. Barriers to free antiretroviral treatment access for female sex workers in Chennai, India.

    PubMed

    Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Kurian, Abraham K; Dubrow, Robert

    2009-11-01

    India's National AIDS Control Organization (NACO) provides free first-line antiretroviral treatment (ART) at government centers for people living with HIV. To assist in developing policies and programs to ensure equity in ART access, we explored barriers to ART access among female sex workers (FSWs) living with HIV in Chennai. Between August and November 2007, we conducted three focus group discussions and two key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family/social, health care system/programmatic, and individual levels. Major barriers included fear of adverse consequences of disclosure of HIV status due to stigma and discrimination associated with HIV and sex work, lack of family support, negative experiences with health care providers, lack of adequate counseling services at government centers and by outreach workers employed by nongovernmental organizations (NGOs), perceived biased treatment of FSWs who are not referred by NGOs, lack of adequate knowledge about ART, and fatalism. Barriers can be addressed by: creating effective measures to reduce stigma associated with HIV/AIDS and sex work at the familial, societal, and health care system levels; incorporating information about ART into targeted interventions among FSWs; training counselors at government hospitals and NGO outreach workers on treatment issues; improving infrastructure and staffing levels at government centers to allow adequate time and privacy for counseling; and implementing government mass media campaigns on ART availability. Finally, it is crucial that NACO begin monitoring ART coverage of FSWs and other marginalized populations to ensure equitable ART access.

  14. Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study.

    PubMed

    Elzi, Luigia; Conen, Anna; Patzen, Annalea; Fehr, Jan; Cavassini, Matthias; Calmy, Alexandra; Schmid, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Battegay, Manuel

    2016-01-01

    Background.  Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods.  Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results.  Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), higher education (OR, 4.03; 95% CI, 2.47-7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20-2.80). Older age (OR, 0.55; 95% CI, .42-.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13-.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998-2001 to 41.2% in 2009-2012, but the employment rates did not increase. Conclusions.  Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV. PMID:26955645

  15. [Combined orthodontic and restorative treatment].

    PubMed

    Kuijpers, M A R; Loomans, B

    2015-11-01

    In patients with agenesis or enamel anomalies in anterior teeth combined orthodontic and restorative treatment is often necessary to achieve an optimal aesthetic result. How both can best be achieved, but also how to maintain the result, requires communication between the dentist and the orthodontist. The orthodontic treatment plan needs to be established in cooperation with the dentist who will carry out the restorative treatment while the patient is at a young age. Since with these young patients, who are still growing craniofacially and whose teeth are still developing, possible future restorative and/or orthodontic treatment, as well as the means of orthodontic retention, need to be included in the treatment plan. In cleft palate patients, it is also important that methods of orthodontic retention of maxillary arch width are given timely attention in the restorative treatment plan because it is especially vulnerable to relapse. PMID:26568998

  16. Analysis of reverse transcriptase and protease genes of HIV for antiretroviral drug resistance in treatment-exposed Jamaican pediatrics.

    PubMed

    Ramkissoon, Adriel P; Amarakoon, Icolyn I; Hamilton, Cindy-Leigh C; Pierre, Russell B; Eyzaguirre, Lindsay M; Carr, Jean K; Blattner, William A; Roye, Marcia E

    2015-09-01

    This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was amplified from 40 samples, sequenced, and analyzed for the identification of antiretroviral resistance-associated mutations (RAMs). All isolates belonged to subtype B and 39 possessed multiple RAMs in the reverse transcriptase genes that would compromise the efficacy of drugs being used to treat these patients. Four isolates possessed RAMs in the protease genes. The overall frequency of HIV drug resistance was 95%. The high frequency of drug resistance is supported by epidemiological data that revealed an equally high frequency of treatment failure (98%) among the study participants. The results of this study indicate the urgent need for greater access to drug resistance testing in Jamaica. PMID:26122980

  17. Derivative Spectrophotometric Method for Estimation of Antiretroviral Drugs in Fixed Dose Combinations

    PubMed Central

    P.B., Mohite; R.B., Pandhare; S.G., Khanage

    2012-01-01

    Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed. PMID:24312779

  18. Growth response to antiretroviral treatment in HIV-infected children: A cohort study from Lilongwe, Malawi

    PubMed Central

    Weigel, Ralf; Phiri, Sam; Chiputula, Fred; Gumulira, Joe; Brinkhof, Martin; Gsponer, Thomas; Tweya, Hannock; Egger, Matthias; Keiser, Olivia

    2013-01-01

    Summary Objective Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. Results A total of 497 children started ART and were followed for 972 person-years. Median age (inter-quartile range; IQR) was 8 years (4 to 11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART median (IQR) WAZ and HAZ increased from −2.1 (−2.7 to −1.3) and −2.6 (−3.6 to −1.8) to −1.4 (−2.1 to −0.8) and −1.8 (−2.4 to −1.1) at 24 months, respectively (p<0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response. PMID:20561308

  19. Early initiation of antiretroviral treatment: Challenges in the Middle East and North Africa

    PubMed Central

    Sardashti, Sara; Samaei, Mehrnoosh; Firouzeh, Mona Mohammadi; Mirshahvalad, Seyed Ali; Pahlaviani, Fatemeh Golsoorat; SeyedAlinaghi, SeyedAhmad

    2015-01-01

    New World Health Organization guidelines recommend the initiation of antiretroviral treatment (ART) for asymptomatic patients with CD4+ T-cell counts of ≤ 500 cells/mm3. Substantial reduction of human immunodeficiency virus (HIV) transmission is addressed as a major public health outcome of this new approach. Middle East and North Africa (MENA), known as the area of controversies in terms of availability of comprehensive data, has shown concentrated epidemics among most of it’s at risk population groups. Serious challenges impede the applicability of new guidelines in the MENA Region. Insufficient resources restrict ART coverage to less than 14%, while only one fourth of the countries had reportable data on patients’ CD4 counts at the time of diagnosis. Clinical guidelines need to be significantly modified to reach practical utility, and surveillance systems have not yet been developed in many countries of MENA. Based on available evidence in several countries people who inject drugs and men who have sex with men are increasingly vulnerable to HIV and viral hepatitis, while their sexual partners - either female sex workers or women in monogamous relationships with high-risk men - are potential bridging populations that are not appropriately addressed by regional programs. Research to monitor the response to ART among the mentioned groups are seriously lacking, while drug resistant HIV strains and limited information on adherence patterns to treatment regimens require urgent recognition by health policymakers. Commitment to defined goals in the fight against HIV, development of innovative methods to improve registration and reporting systems, monitoring and evaluation of current programs followed by cost-effective modifications are proposed as effective steps to be acknowledged by National AIDS Programs of the countries of MENA Region. PMID:25964878

  20. Integrated Pre-Antiretroviral Therapy Screening and Treatment for Tuberculosis and Cryptococcal Antigenemia

    PubMed Central

    Pac, Lincoln; Horwitz, Mara; Namutebi, Anne Marion; Auerbach, Brandon J.; Semeere, Aggrey; Namulema, Teddy; Schwarz, Miriam; Bbosa, Robert; Muruta, Allan; Meya, David; Manabe, Yukari C.

    2015-01-01

    Objective To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) prior to antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up. Methods We enrolled a cohort of HIV-infected, ART-naïve adults with CD4 counts ≤ 250 cells/µL in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤ 100 cells/µL also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART two weeks later. Results Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤ 100 cells/µL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and one patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared to subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤ 10 mg/dL, wasting defined as body mass index ≤ 15.5 kg/m2, and opportunistic infections (TB, positive serum CrAg). Conclusion Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation. PMID:25761234

  1. Public sector antiretroviral treatment programme in South Africa: health care workers' attention to mental health problems.

    PubMed

    Pappin, Michele; Wouters, Edwin; Booysen, Frederik L R; Lund, Crick

    2015-01-01

    Although there is a high prevalence of anxiety and depression amongst people receiving antiretroviral treatment (ART), many patients are not screened, diagnosed or referred for mental health problems. This study aims to determine whether public sector health care workers in South Africa observe, screen, diagnose and refer ART patients that show symptoms of common mental disorders. It also aims to ascertain the extent of mental health training received by public sector health care workers working in ART. The study was cross-sectional in design. Self-administered questionnaires were completed by 40 nurses and structured interviews were conducted with 23 lay workers across the five districts in the Free State between July 2009 and October 2009. STATA version 12 was used to perform statistical data analysis. The health care workers reported observing a high frequency of symptoms of common mental disorders among public sector ART patients. While 70% of nurses screened and diagnosed, only 40% of lay workers screened and diagnosed patients on ART for a mental disorder. Health care workers who had received training in mental health were more likely to screen or diagnose a mental disorder, but only 14% of the workers had received such training. We recommend that health care workers should receive task-specific training to screen and/or diagnose patients on ART for common mental disorders using the guidelines of the South African HIV Clinicians Society. A positive diagnosis should be referred to a health care practitioner for appropriate evidence-based treatment in the form of medication or psychotherapy.

  2. Assessing the population health impact of market interventions to improve access to antiretroviral treatment.

    PubMed

    Bärnighausen, Till; Kyle, Margaret; Salomon, Joshua A; Waning, Brenda

    2012-09-01

    Despite extraordinary global progress in increasing coverage of antiretroviral treatment (ART), the majority of people needing ART currently are not receiving treatment. Both the number of people needing ART and the average ART price per patient-year are expected to increase in coming years, which will dramatically raise funding needs for ART. Several international organizations are using interventions in ART markets to decrease ART price or to improve ART quality, delivery and innovation, with the ultimate goal of improving population health. These organizations need to select those market interventions that are most likely to substantially affect population health outcomes (ex ante assessment) and to evaluate whether implemented interventions have improved health outcomes (ex post assessment). We develop a framework to structure ex ante and ex post assessment of the population health impact of market interventions, which is transmitted through effects in markets and health systems. Ex ante assessment should include evaluation of the safety and efficacy of the ART products whose markets will be affected by the intervention; theoretical consideration of the mechanisms through which the intervention will affect population health; and predictive modelling to estimate the potential population health impact of the intervention. For ex post assessment, analysts need to consider which outcomes to estimate empirically and which to model based on empirical findings and understanding of the economic and biological mechanisms along the causal pathway from market intervention to population health. We discuss methods for ex post assessment and analyse assessment issues (unintended intervention effects, interaction effects between different interventions, and assessment impartiality and cost). We offer seven recommendations for ex ante and ex post assessment of population health impact of market interventions.

  3. Assessing the population health impact of market interventions to improve access to antiretroviral treatment

    PubMed Central

    Bärnighausen, Till; Kyle, Margaret; Salomon, Joshua A; Waning, Brenda

    2012-01-01

    Despite extraordinary global progress in increasing coverage of antiretroviral treatment (ART), the majority of people needing ART currently are not receiving treatment. Both the number of people needing ART and the average ART price per patient-year are expected to increase in coming years, which will dramatically raise funding needs for ART. Several international organizations are using interventions in ART markets to decrease ART price or to improve ART quality, delivery and innovation, with the ultimate goal of improving population health. These organizations need to select those market interventions that are most likely to substantially affect population health outcomes (ex ante assessment) and to evaluate whether implemented interventions have improved health outcomes (ex post assessment). We develop a framework to structure ex ante and ex post assessment of the population health impact of market interventions, which is transmitted through effects in markets and health systems. Ex ante assessment should include evaluation of the safety and efficacy of the ART products whose markets will be affected by the intervention; theoretical consideration of the mechanisms through which the intervention will affect population health; and predictive modelling to estimate the potential population health impact of the intervention. For ex post assessment, analysts need to consider which outcomes to estimate empirically and which to model based on empirical findings and understanding of the economic and biological mechanisms along the causal pathway from market intervention to population health. We discuss methods for ex post assessment and analyse assessment issues (unintended intervention effects, interaction effects between different interventions, and assessment impartiality and cost). We offer seven recommendations for ex ante and ex post assessment of population health impact of market interventions. PMID:21914713

  4. Antiretroviral Treatment Program Retention among HIV-Infected Children in the Democratic Republic of Congo

    PubMed Central

    Ditekemena, John; Luhata, Christophe; Bonane, William; Kiumbu, Modeste; Tshefu, Antoinette; Colebunders, Robert; Koole, Olivier

    2014-01-01

    Background Retaining patients with HIV infection in care is still a major challenge in sub- Saharan Africa, particularly in the Democratic Republic of Congo (DRC) where the antiretroviral treatment (ART) coverage is low. Monitoring retention is an important tool for evaluating the quality of care. Methods and Findings A review of medical records of HIV -infected children was performed in three health facilities in the DRC: the Amo-Congo Health center, the Monkole Clinic in Kinshasa, and the HEAL Africa Clinic in Goma. Medical records of 720 children were included. Kaplan Meier curves were constructed with the probability of retention at 6 months, 1 year, 2 years and 3 years. Retention rates were: 88.2% (95% CI: 85.1%–90.8%) at 6 months; 85% (95% CI: 81.5%–87.6%) at one year; 79.4% (95%CI: 75.5%–82.8%) at two years and 74.7% (95% CI: 70.5%–78.5%) at 3 years. The retention varied across study sites: 88.2%, 66.6% and 92.5% at 6 months; 84%, 59% and 90% at 12 months and 75.7%, 56.3% and 85.8% at 24 months respectively for Amo-Congo/Kasavubu, Monkole facility and HEAL Africa. After multivariable Cox regression four variables remained independently associated with attrition: study site, CD4 cell count <350 cells/µL, children younger than 2 years and children whose caregivers were member of an independent church. Conclusions Attrition remains a challenge for pediatric HIV positive patients in ART programs in DRC. In addition, the low coverage of pediatric treatment exacerbates the situation of pediatric HIV/AIDS. PMID:25541707

  5. Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

    PubMed Central

    Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

    2016-01-01

    Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

  6. Optimizing the new combination treatments.

    PubMed

    Hogan, C

    1996-08-01

    The National Institute of Health's (NIH) Community Programs for Clinical Research on AIDS (CPCRA) working group met in June to explore new treatment options and revisions to health care standards. Protease inhibitors have led to unprecedented effects in clinical trials and show great promise as AIDS treatments. However, little is known about the effect of their long term use, given complicating issues like toxicity and resistance. The group explored the questions of when to start protease inhibitor therapy, with which drug or combination, and when to modify the combination regimen. A consortium of researchers, clinicians, drug company officials, and government representatives, spearheaded by the White House, is working toward a similar standard of treatment. Both groups are exploring ways to design studies for the maximum benefit.

  7. Factors that Influence Adherence to Antiretroviral Treatment in an Urban Population, Jakarta, Indonesia

    PubMed Central

    Weaver, Emma Rosamond Nony; Pane, Masdalina; Wandra, Toni; Windiyaningsih, Cicilia; Herlina; Samaan, Gina

    2014-01-01

    Introduction Although the number of people receiving antiretroviral therapy (ART) in Indonesia has increased in recent years, little is known about the specific characteristics affecting adherence in this population. Indonesia is different from most of its neighbors given that it is a geographically and culturally diverse country, with a large Muslim population. We aimed to identify the current rate of adherence and explore factors that influence ART adherence. Methods Data were collected from ART-prescribed outpatients on an HIV registry at a North Jakarta hospital in 2012. Socio-demographic and behavioral characteristics were explored as factors associated with adherence using logistics regression analyses. Chi squared test was used to compare the difference between proportions. Reasons for missing medication were analyzed descriptively. Results Two hundred and sixty-one patients participated, of whom 77% reported ART adherence in the last 3 months. The level of social support experienced was independently associated with adherence where some social support (p = 0.018) and good social support (p = 0.039) improved adherence compared to poor social support. Frequently cited reasons for not taking ART medication included forgetting to take medication (67%), busy with something else (63%) and asleep at medication time (60%). Discussion This study identified that an increase in the level of social support experienced by ART-prescribed patients was positively associated with adherence. Social support may minimize the impact of stigma among ART prescribed patients. Based on these findings, if social support is not available, alternative support through community-based organizations is recommended to maximize treatment success. PMID:25229671

  8. Long-Term Antiretroviral Treatment Outcomes in Seven Countries in the Caribbean

    PubMed Central

    KOENIG, Serena P; RODRIGUEZ, Luis A; BARTHOLOMEW, Courtenay; EDWARDS, Alison; CARMICHAEL, Tracie E; BARROW, Geoff; CABIÉ, André; HUNTER, Robert; VASQUEZ-MORA, Giselle; QUAVA-JONES, Avion; ADOMAKOH, Nicholas; FIGUEROA, J Peter; LIAUTAUD, Bernard; TORRES, Magaly; PAPE, Jean W

    2012-01-01

    Objectives To report long-term HIV treatment outcomes in 7 Caribbean countries. Design Observational cohort study. Methods We report outcomes for all antiretroviral therapy (ART) naïve adult patients enrolled on ART from program inception until study closing for cohorts in Barbados, the Dominican Republic, Haiti, Jamaica, Martinique, Trinidad, and Puerto Rico. Incidence and predictors of mortality were analyzed by time-to-event approaches. Results 8,203 patients started ART from 1998 to 2008. Median follow-up time was 31 months (interquartile range: 14 to 50 months). Mortality was 13% overall: 6% in Martinique, 8% in Jamaica, 11% in Trinidad, 13% in Haiti, 15% in the Dominican Republic, 15% in Barbados, and 24% in Puerto Rico. Mortality was associated with male gender (HR 1.58; 95% CI: 1.33 – 1.87), body weight (HR 0.85 per 10 pounds; 95% CI: 0.82 – 0.89), hemoglobin (HR 0.84 per g/dl; 95% CI: 0.80 – 0.88), CD4 cell count (0.90 per 50 CD4 cells; 95% CI: 0.86 – 0.93), concurrent TB (HR 1.58; 95% CI: 1.25 – 2.01) and age (HR 1.19 per 10 years; 95% CI: 1.11 – 1.28). After controlling for these variables, mortality in Martinique, Jamaica, Trinidad and Haiti was not significantly different. A total of 75% of patients remained alive and in-care at the end of the study period. Conclusions Long-term mortality rates vary widely across the Caribbean. Much of the difference can be explained by disease severity at ART initiation, nutritional status, and concurrent TB. Earlier ART initiation will be critical to improve outcomes. PMID:22240464

  9. The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States

    PubMed Central

    Long, Elisa F.; Brandeau, Margaret L.; Owens, Douglas K.

    2011-01-01

    Background Although recent guidelines call for expanded routine screening for HIV, resources for antiretroviral treatment (ART) are limited and all eligible people are not currently being treated. Objective To evaluate the effects on the U.S. HIV epidemic of expanded ART, HIV screening, or interventions to reduce risk behavior. Design Dynamic mathematical model of HIV transmission and disease progression, and cost-effectiveness analysis. Data Sources Published literature. Target Population High-risk (injection drug users, men who have sex with men) and low-risk individuals aged 15 to 64 in the U.S. Time Horizon 20 years and lifetime (costs and QALYs). Perspective Societal. Interventions Expanded HIV screening and counseling, treatment with ART, or both. Outcome Measures New HIV infections, discounted costs and quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Results Base-Case Analysis One-time HIV screening of low-risk individuals coupled with annual screening of high-risk individuals could prevent 6.7% of a projected 1.23 million new infections and cost $22,382/QALY gained, assuming a 20% reduction in sexual activity post-screening. Expanding ART utilization to 75% of eligible individuals prevents 10.3% of infections and costs $20,300/QALY gained. A combination strategy prevents 17.3% of infections and costs $21,580/QALY gained. Results Sensitivity Analysis With no reduction in sexual activity, expanded screening prevents 3.7% of infections. Earlier ART initiation when CD4>350 cells/mL prevents 20–28% of infections. Additional efforts to halve high-risk behavior could reduce infections by 65%. Limitations Simplified model of disease progression and treatment; exclusion of acute HIV screening. Conclusions Expanding HIV screening and treatment simultaneously offers the greatest health benefit and is cost-effective. However, even substantial expansion of HIV screening and treatment programs is not sufficient to markedly reduce the U

  10. Genetic Diversity and Drug Resistance Among Antiretroviral Treatment-Failed Individuals from 2010 to 2012 in Honghe, China.

    PubMed

    Yang, Cuixian; Yang, Shaomin; Li, Jianjian; Yang, Bihui; Liu, Jiafa; Li, Huiqin; Bian, Zhongqi

    2015-08-01

    The most common antiretroviral treatment (ART) received by individuals infected with HIV-1 in China is the combination therapy, comprised of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To assess the prevalence of HIV-1 drug resistance and subtypes in Honghe of Yunnan, China, patient plasmas from ART-failed individuals were collected from January 2010 to December 2012. Genotyping was conducted using an in-house assay on patient plasmas. A total of 254 pol sequences were obtained. The prevalence of drug resistance was 47.2% in ART-failed individuals. Of these drug-resistant individuals, 51.7% harbored HIV strains dually resistant to NRTIs and NNRTIs or protease inhibitors (PIs) (34.2% for NNRTIs and 14.2% for NRTIs). Mutations such as M184V, A62V, T69Ins, K103N, Y181C, and G190A were common among the ART-failed individuals. The frequencies of M184V, A62V, and K103N were 20.5%, 11.0%, and 23.6%, respectively. The most common subtypes in Honghe were CRF08_BC (68.50%) and CRF07_BC (12.20%). The subtypes were almost consistent in different time points for one individual. When receiving ART for 6-12 months, the frequency of HIV-1 drug-resistant variants ranked first. This study shows that the high prevalence of HIV drug resistance observed among the ART-failed individuals should be of increasing concern (monitoring of resistance mutations) in ART regions and facilitate developing novel strategies for prevention and control of HIV infection in China. PMID:25919896

  11. Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts

    PubMed Central

    Haas, Andreas D.; Keiser, Olivia; Balestre, Eric; Brown, Steve; Bissagnene, Emmanuel; Chimbetete, Cleophas; Dabis, François; Davies, Mary-Ann; Hoffmann, Christopher J.; Oyaro, Patrick; Parkes-Ratanshi, Rosalind; Reynolds, Steven J.; Sikazwe, Izukanji; Wools-Kaloustian, Kara; Zannou, Djimon Marcel; Wandeler, Gilles; Egger, Matthias

    2015-01-01

    Background HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004–2013. Methods Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. Findings Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine VL, 1·21 (1·13–1·30) for targeted VL and 0·49 (0·43–0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114–133 cells/µl). Interpretation Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing. PMID:26423252

  12. A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment

    PubMed Central

    Johnson, Leigh F; Dorrington, Rob E; Laubscher, Ria; Hoffmann, Christopher J; Wood, Robin; Fox, Matthew P; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, Andrew

    2015-01-01

    Introduction There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods Completeness of death recording was estimated using a capture–recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3–94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2–35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004–2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records. PMID:26685125

  13. Evaluation of combinations of 4'-ethynyl-2-fluoro-2'-deoxyadenosine with clinically used antiretroviral drugs.

    PubMed

    Hachiya, Atsuko; Reeve, Aaron B; Marchand, Bruno; Michailidis, Eleftherios; Ong, Yee Tsuey; Kirby, Karen A; Leslie, Maxwell D; Oka, Shinichi; Kodama, Eiichi N; Rohan, Lisa C; Mitsuya, Hiroaki; Parniak, Michael A; Sarafianos, Stefan G

    2013-06-24

    Drug combination studies of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) with FDA-approved drugs were evaluated by two different methods, MacSynergy II and CalcuSyn. Most of the combinations, including that of the two adenosine analogs EFdA and tenofovir, were essentially additive, without substantial antagonism or synergism. The combination of EFdA and rilpivirine showed apparent synergism. These studies provide information that may be useful for the design of EFdA combination regimens for initial and salvage therapy assessment. PMID:23796932

  14. Success with antiretroviral treatment for children in Kigali, Rwanda: Experience with health center/nurse-based care

    PubMed Central

    van Griensven, Johan; De Naeyer, Ludwig; Uwera, Jeanine; Asiimwe, Anita; Gazille, Claire; Reid, Tony

    2008-01-01

    Background Although a number of studies have shown good results in treating children with antiretroviral drugs (ARVs) in hospital settings, there is limited published information on results in pediatric programs that are nurse-centered and based in health centers, in particular on the psychosocial aspects of care. Methods Program treatment and outcome data were reported from two government-run health centers that were supported by Médecins Sans Frontières (MSF) in Kigali, Rwanda between October 2003 and June 2007. Interviews were held with health center staff and MSF program records were reviewed to describe the organization of the program. Important aspects included adequate training and supervision of nurses to manage ARV treatment. The program also emphasized family-centered care addressing the psychosocial needs of both caregivers and children to encourage early diagnosis, good adherence and follow-up. Results A total of 315 children (< 15 years) were started on ARVs, at a median age of 7.2 years (range: 0.7–14.9). Sixty percent were in WHO clinical stage I/II, with a median CD4% of 14%. Eighty-nine percent (n = 281) started a stavudine-containing regimen, mainly using the adult fixed-dose combination. The median follow-up time after ARV initiation was 2 years (interquartile range 1.2–2.6). Eighty-four percent (n = 265) of children were still on treatment in the program. Thirty (9.5%) were transferred out, eight (2.6%) died and 12 (3.8%) were lost to follow-up. An important feature of the study was that viral loads were done at a median time period of 18 months after starting ARVs and were available for 87% of the children. Of the 174 samples, VL was < 400 copies/ml in 82.8% (n = 144). Two children were started on second-line ARVs. Treatment was changed due to toxicity for 26 children (8.3%), mainly related to nevirapine. Conclusion This report suggests that providing ARVs to children in a health center/nurse-based program is both feasible and very

  15. Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment

    PubMed Central

    Grant, Robert M.; Smith, Dawn K.

    2015-01-01

    Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers. PMID:26512356

  16. Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

    PubMed Central

    2011-01-01

    Background The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions In the combination antiretroviral therapy era, mortality rates

  17. Early Combination Antiretroviral Therapy Limits Exposure to HIV-1 Replication and Cell-Associated HIV-1 DNA Levels in Infants

    PubMed Central

    McManus, Margaret; Mick, Eric; Hudson, Richard; Mofenson, Lynne M.; Sullivan, John L.; Somasundaran, Mohan; Luzuriaga, Katherine

    2016-01-01

    The primary aim of this study was to measure HIV-1 persistence following combination antiretroviral therapy (cART) in infants and children. Peripheral blood mononuclear cell (PBMC) HIV-1 DNA was quantified prior to and after 1 year of cART in 30 children, stratified by time of initiation (early, age <3 months, ET; late, age >3 months-2 years, LT). Pre-therapy PBMC HIV-1 DNA levels correlated with pre-therapy plasma HIV-1 levels (r = 0.59, p<0.001), remaining statistically significant (p = 0.002) after adjustment for prior perinatal antiretroviral exposure and age at cART initiation. PBMC HIV-1 DNA declined significantly after 1 year of cART (Overall: -0.91±0.08 log10 copies per million PBMC, p<0.001; ET: -1.04±0.11 log10 DNA copies per million PBMC, p<0.001; LT: -0.74 ±0.13 log10 DNA copies per million PBMC, p<0.001) but rates of decline did not differ significantly between ET and LT. HIV-1 replication exposure over the first 12 months of cART, estimated as area-under-the-curve (AUC) of circulating plasma HIV-1 RNA levels, was significantly associated with PBMC HIV-1 DNA at one year (r = 0.51, p = 0.004). In 21 children with sustained virologic suppression after 1 year of cART, PBMC HIV-1 DNA levels continued to decline between years 1 and 4 (slope -0.21 log10 DNA copies per million PBMC per year); decline slopes did not differ significantly between ET and LT. PBMC HIV-1 DNA levels at 1 year and 4 years of cART correlated with age at cART initiation (1 year: p = 0.04; 4 years: p = 0.03) and age at virologic control (1 and 4 years, p = 0.02). Altogether, these data indicate that reducing exposure to HIV-1 replication and younger age at cART initiation are associated with lower HIV-1 DNA levels at and after one year of age, supporting the concept that HIV-1 diagnosis and cART initiation in infants should occur as early as possible. PMID:27104621

  18. Correlates of Combination Antiretroviral Adherence Among Recently Diagnosed Older HIV-Infected Adults Between 50 and 64 years

    PubMed Central

    Abara, Winston E.; Adekeye, Oluwatoyosi A.; Xu, Junjun; Heiman, Harry J.; Rust, George

    2016-01-01

    Optimal adherence to combination antiretroviral therapy is essential to the health of older people living with HIV (PLWH), however, the literature on adherence and aging is limited. Using Medicaid data from 29 states (N = 5177), we explored correlates of optimal adherence among older PLWH. The prevalence of optimal adherence was low (32 %) in this study. Males were more adherent than females (APR = 1.11, 95 % CI 1.02–1.21, P = 0.0127); persons with three or more co-morbidities (APR = 0.67, 95 % CI 0.60–0.74, P < 0.001), two co-morbidities (APR = 0.86, 95 % CI 0.75–0.98, P = 0.0319) and one co-morbidity (APR = 0.82, 95 % CI 0.73–0.92, P = 0.0008) were less adherent than those without any co-morbidity; and residents of rural areas (APR = 0.90, 95 % CI 0.63–0.98, P = 0.0385) and small metropolitan areas (APR = 0.82, 95 % CI 0.72–0.94, P = 0.0032) were less adherent than residents of large metropolitan areas. There were no racial differences in optimal adherence. Targeted interventions that provide adherence support, case management, and peer navigation services may be of benefit in achieving optimal adherence in this population. PMID:26885812

  19. Oral lesions among HIV-infected children on antiretroviral treatment in West Africa

    PubMed Central

    Meless, David; Ba, Boubacar; Faye, Malick; Diby, Jean-Serge; N’zoré, Serge; Datté, Sébastien; Diecket, Lucrèce; N’Diaye, Clémentine; Aka, Edmond Addi; Kouakou, Kouadio; Ba, Abou; Ekouévi, Didier Koumavi; Dabis, François; Shiboski, Caroline; Arrivé, Elise

    2014-01-01

    Objectives To estimate the prevalence of oral mucosal diseases and dental caries among HIV-infected children receiving antiretroviral treatment (ART) in West Africa, and to identify factors associated with the prevalence of oral mucosal lesions. Methods Multi-center cross-sectional survey in 5 pediatric HIV clinics in Côte d’Ivoire, Mali and Sénégal. A standardized examination was performed by trained dentists on a random sample of HIV-infected children aged 5 to 15 years receiving ART. The prevalence of oral and dental lesions and mean number of decayed, missing/extracted and filled teeth (DMFdefT) in temporary and permanent dentition were estimated with their 95% confidence interval (95%CI). We used logistic regression to explore the association between children’s characteristics and the prevalence of oral mucosal lesions, expressed as prevalence odds ratio (POR). Results The median age of the 420 children (47% females) enrolled was 10.4 years (interquartile range [IQR]=8.3–12.6). The median duration on ART was 4.6 years (IQR=2.6–6.2); 84 (20.0%) had CD4 count<350 cells/mm3. 35 children (8.3%; 95%CI: [6.1–11.1]) exhibited 42 oral mucosal lesions (24 were candidiasis); 86.0% (95%CI=82.6–89.3) of children had DMFdefT≥1. The presence of oral mucosal lesions was independently associated with CD4 count<350 cells/mm3 (POR=2.96, 95% CI=1.06–4.36) and poor oral hygiene (POR=2.69, 95%CI=1.07–6.76). Conclusions Oral mucosal lesions still occur in HIV-infected African children despite ART, but rarely. However, dental caries were common and severe in this population, reflecting the need to include oral health in the comprehensive care of HIV. PMID:24386972

  20. Socio-economic impact of antiretroviral treatment in HIV patients. An economic review of cost savings after introduction of HAART.

    PubMed

    Gonzalo, Teresa; García Goñi, Manuel; Muñoz-Fernández, María Angeles

    2009-01-01

    Star celebrities such as Rock Hudson, Freddie Mercury, Magic Johnson, and Isaac Asimov have unfortunately something in common: they were all victims of the HIV global pandemic. Since then HIV infection has become considered a pandemic disease, and it is regarded as a priority in healthcare worldwide. It is ranked as the first cause of death among young people in industrialized countries, and it is recognized as a public healthcare problem due to its human, social, mass media, and economic impact. Incorporation of new and highly active antiretroviral treatment, available since 1996 for HIV/AIDS treatment, has provoked a radical change in the disease pattern, as well as in the impact on patient survival and quality of life. The pharmaceutical industry's contribution, based on the research for more active new drugs, has been pivotal. Mortality rates have decreased significantly in 20 years by 50% and now AIDS is considered a chronic and controlled disease. In this review we have studied the impact of HAART treatment on infected patients, allowing them to maintain their status as active workers and the decreased absenteeism from work derived from this, contributing ultimately to overall social wealth and, thus, to economic growth. Furthermore, an analysis of the impact on healthcare costs, quality of life per year, life per year gained, cost economic savings and cost opportunity among other parameters has shown that society and governments are gaining major benefits from the inclusion of antiretroviral therapies in HIV/AIDS patients.

  1. CD4+ guided antiretroviral treatment interruption in HIV infection: a meta-analysis.

    PubMed

    Seminari, Elena; De Silvestri, Annalisa; Boschi, Andrea; Tinelli, Carmine

    2008-01-01

    The aim of this meta-analysis study was to evaluate the relative risk of death or AIDS-defining events associated to CD4+ guided treatment interruption in patients with chronic HIV infection. A search was conducted using PubMed and Cochrane Library; key words for PubMed were: "antiretroviral therapy and interrupt*" in the full papers from January 1, 2000 up to and including December 31, 2007. To limit the publication bias, clinical trials performed on the topic of the meta-analysis were searched also on http://www.clinicaltrial.gov. Inclusion criteria of studies were: starting a CD4+ guided interruption of HAART in HIV chronically infected patients with CD4+ cell count > 350 cells/mm3, age > 13 years old, and absence of concomitant use of immunomodulatory drugs. Using a conservative approach, to be included in the meta-analysis, studies had to have a follow up period > 100 person years to minimize the bias of a too short observation time. The studies were classified into two categories: randomized clinical trial (one arm stops therapy and other arms continues HAART) and cohort studies. For each study measures of effect (hazard ratio or incidence rate ratio) were reported, when available, uncorrected and corrected for potential confounders. Publication bias was assessed graphically through funnel plot. Pooled relative risk and pooled risk difference were calculated by use of a random effects model following the DerSimonian-Laird method. Observational studies were considered separately and the incidence of primary endpoint was evaluated in each study and the cumulative incidence was calculated. Of the 555 full papers found, all abstracts were screened and 58 full text articles for potential inclusion were retrieved and 18 were retained (seven randomized clinical trials and 11 observational studies). In randomized clinical trials, the meta-analysis showed that the pooled relative risk of AIDS-defining event or mortality was 2.50 (95% CI: 1.87-3.34; p < 0.001); the

  2. Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability

    PubMed Central

    2012-01-01

    Background In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions

  3. Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment

    PubMed Central

    Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

    2007-01-01

    Background Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. Methods and Findings We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir–ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six

  4. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation.

  5. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation. PMID:26862469

  6. The Heart in Haart: Quality of Life of Patients Enrolled in the Public Sector Antiretroviral Treatment Programme in the Free State Province of South Africa

    ERIC Educational Resources Information Center

    Booysen, F. Le R.; Van Rensburg, H. C. J.; Bachmann, M.; Louwagie, G.; Fairall, L.

    2007-01-01

    This paper reports on the quality of life of patients enrolled in the public sector antiretroviral treatment programme in the Free State province of South Africa. Statistical analysis of cross-sectional data reveals that it is not access to treatment "per se" that enhances the quality of life of those who have come forward for ART. Rather, it is…

  7. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

    PubMed Central

    Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

    2001-01-01

    In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

  8. Treatment outcomes in a decentralized antiretroviral therapy program: a comparison of two levels of care in north central Nigeria.

    PubMed

    Okonkwo, Prosper; Sagay, Atiene S; Agaba, Patricia A; Yohanna, Stephen; Agbaji, Oche O; Imade, Godwin E; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A; Idoko, John A; Kanki, Phyllis J

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.

  9. Outcome of artemether-lumefantrine treatment for uncomplicated malaria in HIV-infected adult patients on anti-retroviral therapy

    PubMed Central

    2014-01-01

    Background Malaria and HIV infections are both highly prevalent in sub-Saharan Africa, with HIV-infected patients being at higher risks of acquiring malaria. The majority of antiretroviral (ART) and anti-malarial drugs are metabolized by the CYP450 system, creating a chance of drug-drug interaction upon co-administration. Limited data are available on the effectiveness of the artemether-lumefantrine combination (AL) when co-administered with non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this study was to compare anti-malarial treatment responses between HIV-1 infected patients on either nevirapine- or efavirenz-based treatment and those not yet on ART (control-arm) with uncomplicated falciparum malaria, treated with AL. Method This was a prospective, non-randomized, open-label study conducted in Bagamoyo district, with three arms of HIV-infected adults: efavirenz-based treatment arm (EFV-arm) n = 66, nevirapine-based treatment arm (NVP-arm) n = 128, and control-arm n = 75, with uncomplicated malaria. All patients were treated with AL and followed up for 28 days. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with AL by day 28. Results Day 28 ACPR was 97.6%, 82.5% and 94.5% for the NVP-arm, EFV-arm and control-arm, respectively. No early treatment or late parasitological failure was reported. The cumulative risk of recurrent parasitaemia was >19-fold higher in the EFV-arm than in the control-arm (Hazard ratio [HR], 19.11 [95% confidence interval {CI}, 10.5–34.5]; P < 0.01). The cumulative risk of recurrent parasitaemia in the NVP-arm was not significantly higher than in the control-arm ([HR], 2.44 [95% {CI}, 0.79–7.6]; P = 0.53). The median (IQR) day 7 plasma concentrations of lumefantrine for the three arms were: 1,125 ng/m (638.8-1913), 300.4 ng/ml (220.8-343.1) and 970 ng/ml (562.1-1729) for the NVP-arm, the EFV-arm and the control-arm, respectively (P

  10. Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review.

    PubMed

    Katusiime, Christine; Ocama, Ponsiano; Kambugu, Andrew

    2014-09-01

    The effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand with the development of new antiretroviral agents and regimens. However, the successful long-term treatment of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug classes.

  11. "No one can ask me 'Why do you take that stuff?'": men's experiences of antiretroviral treatment in South Africa.

    PubMed

    Fitzgerald, Molly; Collumbien, Martine; Hosegood, Victoria

    2010-03-01

    This paper examines the way gender shaped the health behaviours, health care experiences and narratives of HIV-positive men initiating antiretroviral treatment in South Africa. We conducted participant observation and in-depth, semi-structured interviews with eight men enrolled in a public HIV treatment programme in a rural health district in KwaZulu-Natal. We also interviewed their family members and programme staff. The study found that men's narratives and experiences of antiretroviral therapy (ART) were complex. Descriptions of control and coping juxtaposed with low self-esteem and guilt. Improvements in health following treatment increased optimism about the future but were readily undermined by men's concerns about being unable to meet strongly gendered expectations in relation to family and work. Alcohol use and abuse by men themselves or by family members was found to be an important issue influencing disclosure, uptake and adherence. Given messages discouraging alcohol use during treatment, men reported self-imposed delays to enrolment while they tried to stop or reduce alcohol use, although none had sought advice or professional help in doing so. Men also felt very threatened by alcohol abuse by family members fearing accidental disclose, insults and violence. With regards to health providers, men held strong views as to appropriate and professional behaviour by programme staff, particularly regarding confidentiality. As ART programmes in Africa become established and evolve, we not only need to identify barriers to men's access and adherence but monitor their health and treatment experiences. These findings suggest that the issue of alcohol and ART warrants further investigation. Additional training for primary health care providers and counsellors on health promotion with men may be useful. PMID:20390516

  12. Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384

    PubMed Central

    Robbins, Gregory K.; Spritzler, John G.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Rodriguez, Benigno A.; Skowron, Gail; Skolnik, Paul R.; Shafer, Robert W.; Pollard, Richard B.

    2009-01-01

    Background Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4+ naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (≤350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ≤200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ≤350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts. PMID:19123865

  13. Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort

    PubMed Central

    Scarsi, Kimberly K.; Eisen, Geoffrey; Darin, Kristin M.; Meloni, Seema T.; Rawizza, Holly E.; Tchetgen Tchetgen, Eric J.; Agbaji, Oche O.; Onwujekwe, Daniel I.; Gashau, Wadzani; Nkado, Reuben; Okonkwo, Prosper; Murphy, Robert L.; Kanki, Phyllis J.

    2016-01-01

    Background. Despite sparse efficacy data, tenofovir–emtricitabine or tenofovir–lamivudine plus nevirapine is used in many resource-constrained settings. Methods. This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir–emtricitabine or lamivudine (tenofovir group) or zidovudine–lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. Results. A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21–1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03–1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40–.63) and increasing age (HR, 0.98; 95% CI, .97–.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. Conclusions. Compared with zidovudine–lamivudine, the use of tenofovir–lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection. PMID:26561532

  14. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia

    PubMed Central

    Abdissa, Alemseged; Kæstel, Pernille; Tesfaye, Markos; Yilma, Daniel; Girma, Tsinuel; Wells, Jonathan C K; Ritz, Christian; Mølgaard, Christian; Michaelsen, Kim F; Zerfu, Dilnesaw; Brage, Søren; Andersen, Åse B; Friis, Henrik

    2014-01-01

    Objectives To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. Design Randomised controlled trial. Setting Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. Outcome measures Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. Results Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (−0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (−2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not

  15. The impact of new antiretroviral treatments on college students' intention to use a condom with a new sexual partner.

    PubMed

    Gagnon, M P; Godin, G

    2000-06-01

    The aim of this study was to evaluate possible changes in predisposing factors in sexual preventive behaviors that could result from the availability of an efficient new antiretroviral therapy. A total of 136 young adults were randomly assigned a vignette to read describing AIDS as a lethal or chronic disease. After reading the vignette, the participants completed a self-administered questionnaire assessing the psychosocial determinants of intention to use a condom with a new sexual partner. The variables were measured according to Ajzen's (1985, 1988, 1991) theory of planned behavior and Triandis's (1977) theory of interpersonal behavior. The experimental manipulation was more successful when the disease was described as lethal (66 of the 68 subjects) rather than chronic (30 of the 68 subjects). For the 96 participants who correctly identified the expected outcome of the disease presented in the vignette, a significant difference in intention was found between the two experimental situations (p < .05). Regression of intention to use condoms on the psychosocial variables yielded an adjusted R2 of .62. Perceived behavioral control, social norms, personal normative belief and anticipated affective reaction were the significant variables explaining this intention. The results suggest that intention to use condoms with a new sexual partner is likely to be modified by the expected outcome of the disease, that is, whether lethal or chronic. Thus, it is suggested that interventions aimed at young adults take into account the impacts the new antiretroviral treatments are likely to have on preventive behaviors.

  16. Drug Interactions with New and Investigational Antiretrovirals

    PubMed Central

    Brown, Kevin C.; Paul, Sunita; Kashuba, Angela D.M.

    2010-01-01

    More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat). PMID:19492868

  17. Growth of HIV-Infected Children in the Early Stage of Antiretroviral Treatment: A Retrospective Cohort Study in China.

    PubMed

    Hu, Ran; Mu, Weiwei; Sun, Xin; Wu, Hao; Pang, Lin; Wang, Liming; Zhao, Qingxia; Wu, Yasong; Zhao, Decai; Chen, Meiling; Ma, Ye; Zhang, Fujie

    2016-08-01

    Malnutrition and human immunodeficiency virus (HIV)-related complications are commonly seen in HIV-infected children, and these have been shown in high-prevalent areas such as Africa. Antiviral therapy (ART) has notably controlled disease progression, whereas it effectively reverses underweight and growth retardation in HIV-infected children. This study was conducted to evaluate the growth status after initiation of ART in HIV-infected children in China. A retrospective cohort study was conducted based on the National Science and Technology Major Project. HIV-infected children who initiated antiretroviral treatment between January 1st, 2012 and December 31st, 2012 were followed up to December 31st, 2014. Z-scores of height and weight were calculated by WHO Anthro (plus). Linear mixed-effects models were used to model trajectories of weight- and height-for-age Z-scores. Seven hundred forty-four participants enrolled in the study, with 585 participants and 712 participants who had WAZ (weight-for-age Z-score) and HAZ (height-for-age Z-score), respectively, before initiation of ART. Among them, 125 (21.4%) were underweight and 301 (42.3%) were stunted. After treatment, among the 125 underweight children, WAZ improved in 69 patients, regained more than -2 on average. Among the 301 stunted children, HAZ improved in 123 patients, regained more than -2 on average. WAZ improved for the first 6 months by 0.052 units each month and then stabilized, whereas HAZ consistently improved by 0.014 units each month over time. Antiretroviral treatment reversed the adverse effects of HIV to some degree. Early diagnosis and treatment, with an effective nutrition program, is necessary to improve malnutrition further. PMID:27509236

  18. Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

    PubMed Central

    Anderson, Motswedi; Gaseitsiwe, Simani; Moyo, Sikhulile; Thami, Kerapetse P.; Mohammed, Terence; Setlhare, Ditiro; Sebunya, Theresa K.; Powell, Eleanor A.; Makhema, Joseph; Blackard, Jason T.; Marlink, Richard; Essex, Max; Musonda, Rosemary M.

    2016-01-01

    Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens. PMID:27800524

  19. Adherence as therapeutic citizenship: impact of the history of access to antiretroviral drugs on adherence to treatment.

    PubMed

    Nguyen, Vinh-Kim; Ako, Cyriaque Yapo; Niamba, Pascal; Sylla, Aliou; Tiendrébéogo, Issoufou

    2007-10-01

    A dramatic increase in the use of antiretroviral drugs in Africa has increased focus on adherence to treatment, which has so far been equivalent if not superior to that in northern contexts. The reasons for this exceptional adherence are poorly understood. In this paper, we examine adherence in the historical and ethnographic context of access to treatment in Burkina Faso, Côte d'Ivoire and Mali. Living where there is no social security and minimal, if any, medical care, individuals diagnosed with HIV are faced with the threat of illness, death, ostracism and destitution, and were obliged to negotiate conflicting networks of obligation, reciprocity, and value. HIV and AIDS programmes value efforts to address social, and indeed biological, vulnerability. In contrast, kinship-based social relationships may value individuals in other ways. These conflicting moral economies often intersect in the worlds of people living with HIV. HIV status can be used to claim resources from the public or non-governmental organization programmes. This may interfere with social networks that are the most stable source of material and emotional support. Self-help and empowerment techniques provided effective tools for people living with HIV to fashion themselves into effective advocates. In the early years of the use of antiretroviral therapy (ART), access to treatment was thus mediated by confessional practices and forms of social triage. We introduce the term 'therapeutic citizenship' to describe the way in which people living with HIV appropriate ART as a set of rights and responsibilities to negotiate these at times conflicting moral economies. Exemplary adherence should be viewed through the lens of therapeutic citizenship. PMID:18090265

  20. "Living by the hoe" in the age of treatment: perceptions of household well-being after antiretroviral treatment among family members of persons with AIDS.

    PubMed

    Kaler, Amy; Alibhai, Arif; Kipp, Walter; Rubaale, Tom; Konde-Lule, Joseph

    2010-04-01

    This paper considers the effects of antiretroviral treatment on the households of person with AIDS in western Uganda. Interviews were carried out with 110 co-resident "treatment partners" of people receiving treatment. We discuss these family members' accounts of the impact of sickness, followed by treatment, on their household's livelihood, defined as the activities needed to obtain and process the resources required to sustain the households. The household's ability to muster labour for subsistence agriculture was of paramount concern when family members considered what treatment meant for the households. While they were very happy with the treatment, they said that households have not yet recovered from the shock of AIDS sicknesses. PMID:20162471

  1. Paradoxes in antiretroviral treatment for injecting drug users: access, adherence and structural barriers in Asia and the former Soviet Union.

    PubMed

    Wolfe, Daniel

    2007-08-01

    Offered proper support, injection drug users (IDUs) can achieve the same levels of adherence to and clinical benefit from antiretroviral treatment (ARV) as other patients with HIV. Nonetheless, in countries of Asia and the former Soviet Union where IDUs represent the largest share of HIV cases, IDUs have been disproportionately less likely to receive ARV. While analysis of adherence amongst IDUs has focused on individual patient ability to adhere to medical regimens, HIV treatment systems themselves are in need of examination. Structural impediments to provision of ARV for IDUs include competing, vertical systems of care; compulsory drug treatment and rehabilitation services that often offer neither ARV nor effective treatment for chemical dependence; lack of opiate substitution treatments demonstrated to increase adherence to ARV; and policies that explicitly or implicitly discourage ARV delivery to active IDUs. Labeling active drug users as socially untrustworthy or unproductive, health systems can create a series of paradoxes that ensure confirmation of these stereotypes. Needed reforms include professional education and public campaigns that emphasize IDU capacity for health protection and responsible choice; recognition that the chronic nature of injecting drug use and its links to HIV infection require development of ARV treatment delivery that includes active drug users; and integrated treatment that strengthens links between health providers and builds on, rather than seeks to bypass, IDU social networks and organizations.

  2. "Conditional Scholarships" for HIV/AIDS Health Workers: Educating and Retaining the Workforce to Provide Antiretroviral Treatment in Sub-Saharan Africa. NBER Working Paper No. 13396

    ERIC Educational Resources Information Center

    Barnighausen, Till; Bloom, David E.

    2007-01-01

    Without large increases in the number of health workers to treat HIV/AIDS (HAHW), most developing countries will be unable to achieve universal coverage with antiretroviral treatment (ART), leading to large numbers of potentially avoidable deaths among people living with HIV/AIDS. We use Markov Monte Carlo microsimulation to estimate the expected…

  3. Prevalence and risk factors for efavirenz-based antiretroviral treatment-associated severe vitamin D deficiency: A prospective cohort study.

    PubMed

    Nylén, Hanna; Habtewold, Abiy; Makonnen, Eyasu; Yimer, Getnet; Bertilsson, Leif; Burhenne, Jürgen; Diczfalusy, Ulf; Aklillu, Eleni

    2016-08-01

    Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD.Treatment-naïve Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV coinfected patients, rifampicin-based anti-TB treatment was initiated 4 or 8 weeks before starting cART. Plasma 25-hydroxyvitamin D (25 [OH]D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, 4, 16, and 48 week of cART. Plasma efavirenz concentrations were determined at 4 and 16 weeks of cART.TB-HIV patients had significantly lower plasma 25 (OH)D3 levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load, and high CYP3A activity as measured by plasma 4β-hydroxycholesterol/cholesterol ratios were significant predictors of low 25 (OH)D3 levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79%, and 43% at 4, 16, and 48 weeks of cART, respectively. The median 25 (OH)D3 levels declined from baseline by -40%, -50%, and -14% at 4, 16, and 48 weeks of cART, respectively.In TB-HIV patients, previous anti-TB therapy had no influence on 25 (OH)D3 levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at the 4 and 16 weeks of cART, respectively. Median plasma 25 (OH)D3 declined from baseline by -17% and -21% at week 4 and 16 of cART, respectively.Our results indicate low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations as significant

  4. Factors associated with adherence to antiretroviral therapy for the treatment of HIV-infected women attending an urban care facility.

    PubMed

    Aspeling, Heila E; van Wyk, Neltjie C

    2008-02-01

    Adherence to antiretroviral therapy (ART) is often jeopardized by factors misapprehended by health-care providers. As South Africa is severely affected by HIV and AIDS, identifying factors that influence adherence in this specific context becomes essential. An exploratory and descriptive case study design was used to further explore this subject and to identify factors that could influence adherence to ART. A significant correlation with international data was found. Most participants indicated that their traditional beliefs and customs did not interfere with their adherence to ART, although the lack of HIV education might facilitate reversion to traditional customs. Adequate treatment preparation, comprehensive HIV education and a supportive patient-provider relationship seemed to impact adherence significantly.

  5. Universal antiretroviral therapy for HIV infection: should US treatment guidelines be applied to resource-limited settings?

    PubMed

    Gallant, Joel E; Mehta, Shruti H; Sugarman, Jeremy

    2013-09-01

    US treatment guidelines now recommend antiretroviral therapy (ART) for all persons infected with human immunodeficiency virus (HIV), regardless of CD4 count, both for the benefit of infected individuals and to prevent HIV transmission. In an effort to meet the critical goal of treating all HIV-infected persons worldwide, there is movement toward extrapolating these guidelines and the data supporting them to resource-limited settings. While economic and practical barriers to universal ART are widely recognized, there has been little discussion of the ethical considerations resulting from global disparities in the safety and efficacy of universal ART in these settings. We argue that the risk-benefit considerations for initiating ART are not the same worldwide due to limitations in the ART regimens used, laboratory monitoring, and consistent availability of ART, which raises ethical questions about universally applying US guidelines in resource-limited settings at the present time.

  6. Treatment outcomes in a decentralized antiretroviral therapy program: a comparison of two levels of care in north central Nigeria.

    PubMed

    Okonkwo, Prosper; Sagay, Atiene S; Agaba, Patricia A; Yohanna, Stephen; Agbaji, Oche O; Imade, Godwin E; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A; Idoko, John A; Kanki, Phyllis J

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care. PMID:25028610

  7. Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria

    PubMed Central

    Okonkwo, Prosper; Sagay, Atiene S.; Agaba, Patricia A.; Yohanna, Stephen; Agbaji, Oche O.; Imade, Godwin E.; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A.; Idoko, John A.; Kanki, Phyllis J.

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care. PMID:25028610

  8. HIV related pulmonary arterial hypertension: epidemiology in Africa, physiopathology, and role of antiretroviral treatment.

    PubMed

    Bigna, Jean Joel R; Sime, Paule Sandra D; Koulla-Shiro, Sinata

    2015-01-01

    The development of HIV related pulmonary arterial hypertension (PAH) reduces the probability of survival by half as compared with HIV-infected individuals without HIV related PAH. HIV infected patients have a greater incidence of PAH compared to general population and have a 2500-fold increased risk of developing PAH. It is therefore important to have a recent overview of the problem in Africa, the most HIV affected part of the world (70 % of all HIV infection in the world). First, we discussed the epidemiology of HIV-related PAH in Africa. Second, the current understanding of the HIV-related PAH pathogenesis has been covered. Third, role of highly active antiretroviral therapy on HIV-related PAH has been revisited. There are few data concerning epidemiology of HIV related pulmonary hypertension in Africa leading to necessity to conduct further prospective large studies. The prevalence of PAH among HIV infected people in Africa varies from 5 to 13 %. The prevalence of HIV-related PAH in Africa is notably high compared to those in developed countries and in general population. The pathogenesis of PAH is clearly complex, and probably results from the interaction of multiple modulating genes with environmental factors. The physiopathology includes cytokines secretion increase which induces dysregulation of endothelial and vascular smooth muscle cell growth and imbalance of endogenous vasodilators and constrictors; HIV viral proteins which induces vascular oxidative stress, smooth myocyte proliferation and migration, and endothelial injury and genetic predisposition due to some major histocompatibility complex alleles, particularly HDL-DR6 and HLA-DR5. Histologically, HIV related PAH has the same characteristics with other types PAH. Antiretroviral therapy have a beneficial effect on the outcome of HIV related pulmonary hypertension, but it lacks evidence from large prospective studies.

  9. A Single Quantifiable Viral Load Is Predictive of Virological Failure in Human Immunodeficiency Virus (HIV)-Infected Patients on Combination Antiretroviral Therapy: The Austrian HIV Cohort Study

    PubMed Central

    Leierer, Gisela; Grabmeier-Pfistershammer, Katharina; Steuer, Andrea; Sarcletti, Mario; Geit, Maria; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Rappold, Michaela; Ledergerber, Bruno; Zangerle, Robert

    2016-01-01

    Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subsequent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51–199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06–4.55 and HR = 4.21, 95% CI = 2.15–8.22, respectively). In those with VL 51–199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84–5.39 and HR = 2.52, 95% CI = 0.96–6.60, respectively). Conclusions. These findings support closer monitoring and adherence counseling for patients with a single measurement of quantifiable VL <200 copies/mL. PMID:27419163

  10. Household food insecurity, maternal nutritional status, and infant feeding practices among HIV-infected Ugandan women receiving combination antiretroviral therapy.

    PubMed

    Young, Sera L; Plenty, Albert H J; Luwedde, Flavia A; Natamba, Barnabas K; Natureeba, Paul; Achan, Jane; Mwesigwa, Julia; Ruel, Theodore D; Ades, Veronica; Osterbauer, Beth; Clark, Tamara D; Dorsey, Grant; Charlebois, Edwin D; Kamya, Moses; Havlir, Diane V; Cohan, Deborah L

    2014-11-01

    Household food insecurity (HHFI) may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore described the prevalence of HHFI and explored if it was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. We assessed these outcomes using bivariate and multivariate analyses among 178 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. HHFI was common; the prevalence of severe, moderate, and little to no household hunger was 7.3, 39.9, and 52.8 %, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower body mass index (BMIs) at enrollment (21.3 vs. 22.5, p < 0.01) and prior to delivery (22.6 vs. 23.8, p < 0.01). BMI across time during pregnancy, but not gestational weight gain, was significantly lower for MSHH [adjusted beta (95 % CI) -0.79 (-1.56, -0.02), p = 0.04; -2.06 (-4.31, 0.19), p = 0.07], respectively. The prevalence (95 % CI) of EBF at 6 months was 67.2 % (59.7-73.5 %), and the proportion of women BF at 12 months was 80.4 % (73.3-85.7 %). MSHH was not associated with prevalence of EBF at 6 months or BF at 12 months. However, among those women still EBF at 4 months (81.4 % of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR 2.38, 95 % CI 1.02-5.58). The prevalence of HHFI, maternal malnutrition, and suboptimal infant feeding practices are high and the causal relationships among these phenomena must be further explored.

  11. Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.

    PubMed

    Dickinson, Laura; Khoo, Saye; Back, David

    2010-01-01

    Current antiretroviral treatment has allowed HIV infection to become a chronic manageable condition with many HIV patients living longer. However, available antiretrovirals are not without limitations, for example the development of resistance and adverse effects. Consequently, new drugs in existing and novel classes are urgently required to provide viable treatment options to patients with few remaining choices. Darunavir, etravirine, maraviroc and raltegravir have been recently approved for treatment-experienced patients and other agents such as rilpivirine, vicriviroc and elvitegravir are currently under phase III study. Clinical studies are necessary to optimise potential treatment combinations and to manage drug-drug interactions to help avoid toxicity or therapy failure. This review aims to summarise the pharmacokinetics and key drug-drug interaction studies for newly available antiretrovirals and those in development. Further information regarding drug-drug interactions of well established antiretrovirals and those recently approved are readily available online at sites such as http://www.hiv-druginteractions.org, http://www.clinicaloptions.com/hiv, http://hivinsite.ucsf.edu. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.

  12. Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course antiretroviral treatment for prevention of maternal–infant transmission

    PubMed Central

    Kuhn, L; Meddows-Taylor, S; Gray, G; Trabattoni, D; Clerici, M; Shearer, G M; Tiemessen, C

    2001-01-01

    T-helper cell responses to HIV have been associated with protection against maternal-infant HIV transmission in the absence of antiretroviral treatment, but the effects of antiretroviral treatment, now widely used for prevention, on development of these cell-mediated responses is unknown. We tested whether development of T-helper cell responses to HIV and other antigens would be affected by exposure to short-course regimens of zidovudine-lamivudine (ZDV-3TC) given to prevent maternal-infant HIV transmission. Cord blood samples were collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in which they were treated with regimens of ZDV-3TC and from 29 infants whose HIV-infected mothers were not treated with any antiretroviral drugs. T-helper cell reactivity to HIV envelope peptides and other antigens was measured in vitro using a sensitive culture supernatant titration assay based on IL-2-dependent proliferation. Infants in the clinical trial were followed to 18 months to determine their HIV infection status, and venous blood samples were re-tested at 4·5 and 9 months for T-cell reactivity to HIV. HIV-stimulated T-helper cell reactivity in cord blood was detected 10-fold less frequently among those exposed to antiretroviral prophylaxis (2·4%) than among those unexposed (24·1%) (P = 0·007). Reductions in HIV-stimulated responses in cord blood occurred despite detectable HIV RNA (mean 3·38 standard deviation 0·76 log10 copies per ml) at delivery among treated women and occurred independent of treatment duration. Our results suggest that short-course antiretroviral treatment given to prevent maternal-infant HIV transmission may attenuate HIV-stimulated T-cell memory responses in the neonate. PMID:11298132

  13. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

    PubMed Central

    2011-01-01

    Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a

  14. Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

    PubMed

    Bolsewicz, K; Debattista, J; Vallely, A; Whittaker, A; Fitzgerald, L

    2015-01-01

    International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of

  15. Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

    PubMed

    Bolsewicz, K; Debattista, J; Vallely, A; Whittaker, A; Fitzgerald, L

    2015-01-01

    International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of

  16. HIV Treatment as Prevention: Modelling the Cost of Antiretroviral Treatment—State of the Art and Future Directions

    PubMed Central

    Meyer-Rath, Gesine; Over, Mead

    2012-01-01

    Policy discussions about the feasibility of massively scaling up antiretroviral therapy (ART) to reduce HIV transmission and incidence hinge on accurately projecting the cost of such scale-up in comparison to the benefits from reduced HIV incidence and mortality. We review the available literature on modelled estimates of the cost of providing ART to different populations around the world, and suggest alternative methods of characterising cost when modelling several decades into the future. In past economic analyses of ART provision, costs were often assumed to vary by disease stage and treatment regimen, but for treatment as prevention, in particular, most analyses assume a uniform cost per patient. This approach disregards variables that can affect unit cost, such as differences in factor prices (i.e., the prices of supplies and services) and the scale and scope of operations (i.e., the sizes and types of facilities providing ART). We discuss several of these variables, and then present a worked example of a flexible cost function used to determine the effect of scale on the cost of a proposed scale-up of treatment as prevention in South Africa. Adjusting previously estimated costs of universal testing and treatment in South Africa for diseconomies of small scale, i.e., more patients being treated in smaller facilities, adds 42% to the expected future cost of the intervention. PMID:22802731

  17. HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda

    PubMed Central

    Sigaloff, Kim Catherina Eve; Boender, Tamara Sonia; Kaudha, Elizabeth; Kayiwa, Joshua; Musiime, Victor; Mukuye, Andrew; Kiconco, Mary; Nankya, Immaculate; Nakatudde-Katumba, Llilian; Calis, Job C.J.; Rinke de Wit, Tobias F.; Mugyenyi, Peter N.

    2016-01-01

    Abstract Background: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda. Methods: At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011. Before starting ART, blood was collected for viral load and pol gene sequencing. Drug resistance mutations were determined using the 2010 International AIDS Society–USA mutation list. Risk factors for HIVDR were assessed with multivariate regression analysis. Results: Three hundred nineteen HIV-infected children with a median age of 4.9 years were enrolled. Sequencing was successful in 279 children (87.5%). HIVDR was present in 10% of all children and 15.2% of children <3 years. Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI), and dual-class resistance was present in 5.7%, 7.5%, and 3.2%, respectively. HIVDR occurred in 35.7% of prevention of mother-to-child transmission (PMTCT)–exposed children, 15.6% in children with unknown PMTCT history, and 7.7% among antiretroviral-naive children. History of PMTCT exposure [adjusted odds ratio (AOR): 2.6, 95% CI: 1.3–5.1] or unknown PMTCT status (AOR: 3.8, 95% CI: 1.1–13.5), low CD4 (AOR: 2.2, 95% CI: 1.3–3.6), current breastfeeding (AOR: 7.4, 95% CI: 2.6–21), and current maternal ART use (AOR: 6.4, 95% CI: 3.4–11.9) emerged as risk factors for primary HIVDR in multivariate analysis. Conclusion: Pretreatment HIVDR is high, especially in children with PMTCT exposure. Protease inhibitor (PI)–based regimens are advocated by the World Health Organization, but availability in children is limited. Children with (unknown) PMTCT exposure, low CD4 count, current breastfeeding, or maternal ART need to be prioritized to receive PI-based regimens. PMID:26723018

  18. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment.

    PubMed

    Nason, Martha C; Patel, Eshan U; Kirkpatrick, Allison R; Prodger, Jessica L; Shahabi, Kamnoosh; Tobian, Aaron A R; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H; Quinn, Thomas C; Serwadda, David; Reynolds, Steven J; Redd, Andrew D

    2016-03-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation. PMID:27191006

  19. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment.

    PubMed

    Nason, Martha C; Patel, Eshan U; Kirkpatrick, Allison R; Prodger, Jessica L; Shahabi, Kamnoosh; Tobian, Aaron A R; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H; Quinn, Thomas C; Serwadda, David; Reynolds, Steven J; Redd, Andrew D

    2016-03-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.

  20. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment

    PubMed Central

    Nason, Martha C.; Patel, Eshan U.; Kirkpatrick, Allison R.; Prodger, Jessica L.; Shahabi, Kamnoosh; Tobian, Aaron A. R.; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.; Redd, Andrew D.

    2016-01-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation. PMID:27191006

  1. The relationship between depression, anxiety and medication adherence among patients receiving antiretroviral treatment in South Africa.

    PubMed

    Nel, Adriaan; Kagee, Ashraf

    2013-08-01

    In recent years, a small but growing body of literature on the associations between common mental disorders and adherence to antiretroviral therapy (ART) has emerged. The present study builds on the growing body of research by investigating associations between symptoms of depression, symptoms of anxiety and adherence to ART. We studied a convenience sample of 101 South African ART users to determine the severity of symptoms of depression and anxiety and their association with self-reported adherence to ART. Based on the standardised cut-off scores recorded using the Beck Depression Inventory - Second Edition (BDI II), 40.4% of participants demonstrated moderate to severe symptoms of depression. Moreover, results from the Beck Anxiety Inventory (BAI) indicated that 28.7% of the study participants demonstrated moderate to severe symptoms of anxiety. Biserial correlations and logistic regression analysis demonstrated a significant relationship between symptoms of depression and adherence. The results indicate that patients reporting non-perfect adherence were approximately three times more likely (OR=2.73; CI=1.09-6.82) to have moderate to severe symptoms of depression than those reporting perfect adherence. The present findings are in keeping with those of previous studies, suggesting that depression may act as a barrier to ART adherence.

  2. HLA Immunogenotype Determines Persistent Human Papillomavirus Virus Infection in HIV-Infected Patients Receiving Antiretroviral Treatment.

    PubMed

    Meys, Rhonda; Purdie, Karin J; de Koning, Maurits N C; Quint, Koen D; Little, Ann-Margaret; Baker, Finnuala; Francis, Nick; Asboe, David; Hawkins, David; Marsh, Steven G E; Harwood, Catherine A; Gotch, Frances M; Bunker, Christopher B

    2016-06-01

    A proportion of human immunodeficiency virus (HIV)-infected patients develop persistent, stigmatizing human papillomavirus (HPV)-related cutaneous and genital warts and anogenital (pre)cancer. This is the first study to investigate immunogenetic variations that might account for HPV susceptibility and the largest to date to categorize the HPV types associated with cutaneous warts in HIV-positive patients. The HLA class I and II allele distribution was analyzed in 49 antiretroviral (ART)-treated HIV-positive patients with persistent warts, 42 noninfected controls, and 46 HIV-positive controls. The allele HLA-B*44 was more frequently identified in HIV-positive patients with warts (P = .004); a susceptible haplotype (HLA-B*44, HLA-C*05; P = .001) and protective genes (HLA-DQB1*06; P = .03) may also contribute. Cutaneous wart biopsy specimens from HIV-positive patients harbored common wart types HPV27/57, the unusual wart type HPV7, and an excess of Betapapillomavirus types (P = .002), compared with wart specimens from noninfected controls. These findings suggest that HLA testing might assist in stratifying those patients in whom vaccination should be recommended. PMID:26908737

  3. Keeping kids in care: virological failure in a paediatric antiretroviral clinic and suggestions for improving treatment outcomes.

    PubMed

    Purchase, Susan; Cunningham, Jayne; Esser, Monika; Skinner, Donald

    2016-09-01

    The burden of paediatric HIV in South Africa is extremely high. Antiretrovirals (ARVs) are now widely accessible in the country and the clinical emphasis has shifted from initiation of treatment to retention in care. This study describes the cumulative virological failure rate amongst children on ARVs in a peri-urban clinic, and suggests ways in which clinics and partners could improve treatment outcomes. The study was conducted by the non-profit organisation HOPE Cape Town Association. A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all children with a viral load >1000 copies/ml, children on monotherapy, children who had stopped treatment, children lost to follow-up (LTFU) and children who had died. Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care. Cumulative virological failure rate was 42%, with most of those children having been LTFU. Both staff and caregivers consistently identified pharmacy queues, ongoing stigma and unpalatable ARVs as barriers to adherence. Staff suggestions included use of adherence aids, and better education and support groups for caregivers. Caregivers also requested support groups, as well as "same day" appointments for caregivers and children, but rejected the idea of home visits. Simple, acceptable and cost-effective strategies exist whereby clinics and their partners could significantly reduce the cumulative virological failure rate in paediatric ARV clinics. These include actively tracing defaulters, improving education, providing support groups, and campaigning for palatable ARV formulations.

  4. Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?

    PubMed Central

    2016-01-01

    Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART’s prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created. PMID:27716813

  5. Containment of simian immunodeficiency virus infection: cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment.

    PubMed

    Lifson, J D; Rossio, J L; Arnaout, R; Li, L; Parks, T L; Schneider, D K; Kiser, R F; Coalter, V J; Walsh, G; Imming, R J; Fisher, B; Flynn, B M; Bischofberger, N; Piatak, M; Hirsch, V M; Nowak, M A; Wodarz, D

    2000-03-01

    To better understand the viral and host factors involved in the establishment of persistent productive infection by primate lentiviruses, we varied the time of initiation and duration of postinoculation antiretroviral treatment with tenofovir (9-[2-(R)-(phosphonomethoxy)propyl]adenine) while performing intensive virologic and immunologic monitoring in rhesus macaques, inoculated intravenously with simian immunodeficiency virus SIVsmE660. Postinoculation treatment did not block the initial infection, but we identified treatment regimens that prevented the establishment of persistent productive infection, as judged by the absence of measurable plasma viremia following drug discontinuation. While immune responses were heterogeneous, animals in which treatment resulted in prevention of persistent productive infection showed a higher frequency and higher levels of SIV-specific lymphocyte proliferative responses during the treatment period compared to control animals, despite the absence of either detectable plasma viremia or seroconversion. Animals protected from the initial establishment of persistent productive infection were also relatively or completely protected from subsequent homologous rechallenge. Even postinoculation treatment regimens that did not prevent establishment of persistent infection resulted in downmodulation of the level of plasma viremia following treatment cessation, compared to the viremia seen in untreated control animals, animals treated with regimens known to be ineffective, or the cumulative experience with the natural history of plasma viremia following infection with SIVsmE660. The results suggest that the host may be able to effectively control SIV infection if the initial exposure occurs under favorable conditions of low viral burden and in the absence of ongoing high level cytopathic infection of responding cells. These findings may be particularly important in relation to prospects for control of primate lentiviruses in the settings of

  6. Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

    PubMed Central

    Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

    2011-01-01

    Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

  7. Sexual behaviour among people with HIV according to self-reported antiretroviral treatment and viral load status

    PubMed Central

    Lampe, Fiona C.

    2016-01-01

    Objective: To assess, among people with HIV, the association of self-reported antiretroviral treatment (ART) and viral load status with condomless sex with an HIV-serodifferent partner (CLS-D). Design: Cross-sectional study of 3258 HIV-diagnosed adults in the United Kingdom, 2011–2012. Methods: CLS-D in the past 3 months and self-reported ART/viral load were ascertained by questionnaire. Clinic-recorded viral load was documented. HIV-transmission risk sex (CLS-D-HIV-risk) was defined as CLS-D together with either not on ART or clinic-recorded viral load more than 50 copies/ml. Results: Of 3178 participants diagnosed more than 3 months ago, 2746 (87.9%) were on ART, of whom self-reported viral load was ‘50 copies/ml/ or less/undetectable’ for 78.4%; ‘more than 50 copies/ml/detectable’ for 8.3%; ‘do not know/missing’ for 13.3%. CLS-D prevalence was 14.9% (326/2189), 6.4% (23/360) and 10.7% (67/629) among men who have sex with men, heterosexual men and women, respectively. Among men who have sex with men, CLS-D prevalence was 18.8% among those not on ART; 15.2% among those on ART with undetectable self-reported viral load; 9.8% among those on ART without undetectable self-reported viral load. Compared with ‘on ART with undetectable self-reported viral load’, prevalence ratios (95% confidence interval) adjusted for demographic/HIV-related factors were: 0.66 (0.45, 0.95) for ‘on ART without undetectable self-reported viral load’, and 1.08 (0.78, 1.49) for ‘not on ART’ (global P = 0.021). Among heterosexual men and women (combined), ART/self-reported viral load was not associated with CLS-D [corresponding adjusted prevalence ratios: 1.14 (0.73, 1.79) for ‘on ART without undetectable self-reported viral load’; 0.88 (0.44, 1.77) for ‘not on ART’, P = 0.77]. CLS-D-HIV-risk prevalence was 3.2% among all participants; 16.1% for ‘not on ART’; 0.6% for ‘on ART with undetectable self-reported viral load; 4.2% for ‘on ART

  8. Challenges in initiating antiretroviral therapy in 2010.

    PubMed

    Tremblay, Cécile L; Baril, Jean-Guy; Fletcher, David; Kilby, Donald; Macpherson, Paul; Shafran, Stephen D; Tyndall, Mark W

    2010-08-01

    Many clinical trials have shown that initiating antiretroviral therapy (ART) at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient's preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

  9. Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation

    PubMed Central

    Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W.; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C.; Currier, Judith S.; Tang, Alice M.; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

    2015-01-01

    Background. Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. Methods. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥10 mg/L) with clinical failure were assessed using multivariable Cox models. Results. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82–14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37–1.58) for anemia without inflammation, and 0.45 (95% CI, .11–1.80) for inflammation without anemia compared to those without anemia and inflammation. Conclusions. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent

  10. Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India - the HIVIND study protocol

    PubMed Central

    2010-01-01

    Background Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV. Although different adherence-supporting interventions have been reported, their long term feasibility in low income settings remains uncertain. Thus, there is a need to explore sustainable contextual adherence aids in such settings, and to test these using rigorous scientific designs. The current ubiquity of mobile phones in many resource-constrained settings, make it a contextually appropriate and relatively low cost means of supporting adherence. In India, mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications. This paper presents the study protocol for a trial, to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India. Methods/Design 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India. Patients will be randomized into control and intervention arms. The control arm will receive the standard of care; the intervention arm will receive the standard of care plus mobile phone reminders. Each reminder will take the form of an automated call and a picture message. Reminders will be delivered once a week, at a time chosen by the patient. Patients will be followed up for 24 months or till the primary outcome i.e. virological failure, is reached, whichever is earlier. Self-reported adherence is a secondary outcome. Analysis is by intention-to-treat. A cost-effectiveness study of the intervention will also be carried out. Discussion Stepping up telecommunications technology in resource-limited healthcare settings is a priority of the World Health Organization. The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line antiretrovirals in an Indian context

  11. Survival of people on antiretroviral treatment in Zambia: a retrospective cohort analysis of HIV clients on ART

    PubMed Central

    Amanzi, Patrick; Michelo, Charles; Simoonga, Christopher; Dambe, Rosalia; Chongwe, Gershom

    2016-01-01

    Introduction Provision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival. Methods The study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight. Results Results showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART. Conclusion This study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged. PMID:27642482

  12. Utilization of medical treatments and adherence to antiretroviral therapy among HIV-positive adults with histories of childhood sexual abuse.

    PubMed

    Meade, Christina S; Hansen, Nathan B; Kochman, Arlene; Sikkema, Kathleen J

    2009-04-01

    HIV is a chronic, life-threatening illness that necessitates regular and consistent medical care. Childhood sexual abuse (CSA) is a common experience among HIV-positive adults and may interfere with treatment utilization. This study examined rates and correlates of treatment utilization among HIV-positive adults with CSA enrolled in a coping intervention trial in New York City. The baseline assessment included measures of treatment utilization, mental health, substance abuse, and other psychosocial factors. In 2002-2004, participants (50% female, 69% African-American, M = 42.3 +/- 6.8 years old) were recruited. Nearly all (99%) received HIV medical care. However, 20% had no outpatient visits and 24% sought emergency services in the past 4 months. Among 184 participants receiving antiretroviral therapy (ART), 22% were less than 90% adherent in the past week. In a multivariable logistic regression model, no outpatient treatment was associated with African American race (AOR = 3.46 [1.42-8.40]), poor social support (AOR = 1.59 [1.03-2.45]), and abstinence from illicit drug use (AOR = 0.37 [0.16-0.85]). Emergency service utilization was associated with HIV symptoms (AOR = 2.30 [1.22-4.35]), binge drinking (AOR=2.92 (1.18-7.24)), and illicit drug use (AOR = 1.98 [1.02-3.85]). Poor medication adherence was associated with trauma symptoms (AOR = 2.64 [1.07-6.75]) and poor social support (AOR = 1.82 [1.09-2.97]). In sum, while participants had access to HIV medical care, a sizable minority did not adhere to recommended guidelines and thus may not be benefiting optimally from treatment. Interventions targeting HIV-positive adults with CSA histories may need to address trauma symptoms, substance abuse, and poor social support that interfere with medical treatment utilization and adherence.

  13. Correlates of Adherence and Treatment Failure Among Kenyan Patients on Long-term Highly Active Anti-Retroviral Therapy

    PubMed Central

    Ochieng, Washingtone; Kitawi, Rose C.; Nzomo, Timothy J.; Mwatelah, Ruth S.; Kimulwo, Maureen J.; Ochieng, Dorothy J.; Kinyua, Joyceline; Lagat, Nancy; Onyango, Kevin O.; Lwembe, Raphael M.; Mwamburi, Mkaya; Ogutu, Bernhards R.; Oloo, Florence A.; Aman, Rashid

    2015-01-01

    Background Universal access to highly active antiretroviral therapy (HAART) is still elusive in most developing nations. We asked whether peer support influenced adherence and treatment outcome and if a single viral load (VL) could define treatment failure in a resource-limited setting. Methods A multi-center longitudinal and cross-sectional survey of VL, CD4 T-cells and adherence in 546 patients receiving HAART for up to 228 months. VL and CD4 counts were determined using m2000 Abbott RealTime HIV-1 assay and FACS respectively. Adherence was assessed based on pill-count and on self-report. Results Respectively, 55.8%, 22.2% and 22% of the patients had good, fair and poor adherence. Adherence, peer support and regimen but not HIV disclosure, age or gender, independently correlated with VL and durability of treatment in a multivariate analysis (p<0.001). Treatment failure was 35.9% using sequential VL but ranged between 27% and 35% using alternate single VL cross-sectional definitions. More patients failed stavudine (41.2%) than zidovudine (37.4%) or tenofovir (28.8%, P=0.043) treatment arms. Peer support correlated positively with adherence (χ2, p<0.001), with non-adherence highest in the stavudine arm. VL before the time of regimen switch was comparable between patients switching and those not switching treatment. Moreover, 36% of those switching still failed second-line regimen. Conclusion Weak adherence support and inaccessible VL testing threaten to compromise the success of HAART scale-up in Kenya. To hasten ART monitoring and decision-making, we suggest strengthening patient-focused adherence programs, optimizing and aligning regimen to WHO standards, and a single point-of-care VL testing when multiple tests are unavailable. PMID:26009836

  14. Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

    PubMed Central

    Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Anthony, Patricia; Thuvamontolrat, Kasalyn; Pahwa, Savita; Burchett, Sandra; Weinberg, Adriana; Kovacs, Andrea

    2015-01-01

    Background We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Methods Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system. PMID:25794163

  15. Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in Mexico

    PubMed Central

    Tilghman, Myres W.; Guerena, Don Diego; Licea, Alexei; Pérez-Santiago, Josué; Richman, Douglas D.; May, Susanne; Smith, Davey M.

    2010-01-01

    Background Similar to other resource-limited settings, cost restricts availability of viral load monitoring for most patients receiving antiretroviral therapy in Tijuana, Mexico. We evaluated if a pooling method could improve efficiency and reduce costs while maintaining accuracy. Methods We evaluated 700 patient blood plasma specimens at a reference laboratory in Tijuana for detectable viremia, individually and in 10 × 10 matrix pools. Thresholds for virologic failure were set at ≥500, ≥1000 and ≥1500 HIV RNA copies per milliliter. Detectable pools were deconvoluted using pre-set algorithms. Accuracy and efficiency of the pooling method were compared with individual testing. Quality assurance (QA) measures were evaluated after 1 matrix demonstrated low efficiency relative to individual testing. Results Twenty-two percent of the cohort had detectable HIV RNA (≥50 copies/mL). Pooling methods saved approximately one third of viral load assays over individual testing, while maintaining negative predictive values of >90% to detect samples with virologic failure (≥50 copies/mL). One matrix with low relative efficiency would have been detected earlier using the developed QA measures, but its exclusion would have only increased relative efficiency from 39% to 42%. These methods would have saved between $13,223 and $14,308 for monitoring this cohort. Conclusions Despite limited clinical data, high prevalence of detectable viral loads and a contaminated matrix, pooling greatly improved efficiency of virologic monitoring while maintaining accuracy. By improving cost-effectiveness, these methods could provide sustainability of virologic monitoring in resource-limited settings, and incorporation of developed QA measures will most likely maximize pooling efficiency in future uses. PMID:21124228

  16. Association of Hypercholesterolemia Incidence With Antiretroviral Treatment, Including Protease Inhibitors, Among Perinatally HIV-Infected Children

    PubMed Central

    Tassiopoulos, Katherine; Williams, Paige L.; Seage, George R.; Crain, Marilyn; Oleske, James; Farley, John

    2011-01-01

    Context Antiretroviral therapy has been associated with hypercholesterolemia in HIV-infected children. Few longitudinal studies have been conducted to examine this association, however. Objective To evaluate the incidence of and risk factors for development of hypercholesterolemia in a large pediatric study. Design Prospective cohort study (Pediatric AIDS Clinical Trials Group 219C). Participants A total of 2122 perinatally HIV-infected children free of hypercholesterolemia at entry. Outcome Development of hypercholesterolemia (total cholesterol ≥220 mg/dL at 2 consecutive visits). Cox proportional hazards models were used to evaluate risk factors. Results Thirteen percent of children had hypercholesterolemia at entry, and an additional 13% developed hypercholesterolemia during follow-up for an incidence rate of 3.4 cases per 100 person-years (95% confidence interval [CI]: 3.0 to 3.9). After adjustment for age, boosted protease inhibitor (PI) use (hazard ratio [HR] = 13.9, 95% CI: 6.73 to 28.6), nonboosted PI use (HR = 8.65, 95% CI: 4.19 to 17.9), and nonnucleoside reverse transcriptase inhibitor use (HR = 1.33, 95% CI: 1.04 to 1.71) were associated with increased risk of hypercholesterolemia, and higher viral load was protective (>50,000 vs. ≤400 copies/mL; HR = 0.59, 95% CI: 0.39 to 0.90). Self-reported adherent subjects had higher risk. Conclusions PIs were significant risk factors for hypercholesterolemia. Higher viral load was protective and may reflect non-adherence. Further follow-up is critical to evaluate long-term consequences of chronic PI exposure and hypercholesterolemia. PMID:18209684

  17. Antiretroviral Treatment Interruption and Loss to Follow-Up in Two HIV Cohorts in Australia and Asia: Implications for ‘Test and Treat’ Prevention Strategy

    PubMed Central

    Wand, Handan; McManus, Hamish; Vonthanak, Saphonn; Woolley, Ian; Honda, Miwako; Read, Tim; Sirisanthana, Thira; Zhou, Julian; Carr, on behalf of Australia HIV Observational Database (AHOD) and Treat Asia HIV Observation Database (TAHOD), Andrew

    2013-01-01

    Abstract Both antiretroviral treatment interruption (TI) and cessation have been strongly discouraged since 2006. We describe the incidence, duration, and risk factors for TI and loss-to-follow-up (LTFU) rates across 13 countries. All 4689 adults (76% men) in two large HIV cohorts in Australia and Asia commencing combination antiretroviral therapy (ART) to March 2010 were included. TI was defined by ART cessation >30 days, then recommencement, and loss to follow-up (LTFU) by no visit since 31 March 2009 and no record of death. Survival analysis and Poisson regression methods were used. With median follow-up of 4.4 years [interquartile range (IQR):2.1–6.5], TI incidence was 6.7 per 100 person years (PY) (95% CI:6.1–7.3) pre-2006, falling to 2.0 (95% CI:1.7–2.2) from 2006 (p<0.01). LTFU incidence was 3.5 per 100 PY (95% CI:3.1–3.9) pre-2006, and 4.1 (95% CI:3.5–4.9) from 2006 (p=0.22). TIs accounted for 6.4% of potential time on ART pre-2006 and 1.2% from 2006 (p<0.01), and LTFU 4.7% of potential time on ART pre-2006 and 6.6% from 2006 (p<0.01). Median TI duration was 163 (IQR: 75–391) days pre-2006 and 118 (IQR: 67–270) days from 2006 (p<0.01). Independent risk factors for the first TI were: Australia HIV Observational Database participation; ART initiation pre-2006; ART regimens including stavudine and didanosine; three nucleoside analogue reverse transcriptase inhibitors; ≥7 pills per day; and ART with food restrictions (fasting or with food). In conclusion, since 2006, 7.8% of patients had significant time off treatment, which has the potential to compromise any ‘test and treat’ policy as during the interruption viral load will rebound and increase the risk of transmission. PMID:24320013

  18. Treatment Buddies Improve Clinic Attendance among Women but Not Men on Antiretroviral Therapy in the Nyanza Region of Kenya

    PubMed Central

    Kibaara, Charles; Blat, Cinthia; Shade, Starley; Mbullo, Patrick; Bukusi, Elizabeth A.

    2016-01-01

    Background. Kenyan antiretroviral (ART) guidelines encourage treatment buddies (TBy) to maximize treatment adherence. This study examined the effect of TBys on clinic attendance in men and women on ART. Methods. This retrospective cohort study included all adult patients initiating ART from August 2007 to December 2011 at four health facilities in Kenya. Data were abstracted from electronic medical records and analyzed using Poisson regression. Results. Of 2,430 patients, 2,199 (91%) had a TBy. Relationship between TBy and clinic attendance differed in females and males (interaction p = 0.09). After demographic and clinic factor adjustment, females with a TBy were 28% more likely to adhere to all appointments than those without (adjusted aRR = 1.28; 95% CI 1.08–1.53), whereas males were no more likely to adhere (aRR = 1.01; 95% CI 0.76–1.32). Males reported partner/spouse (33%) or brother (11%) as the TBy while females reported sister (17%), partner/spouse (14%), or another family member (12%). Multivariable analysis found no association between clinic attendance and TBy relationship in either gender. Conclusion. Clinic attendance was higher among women with TBys but not men. Results support TBys to help women achieve ART success; alternate strategies to bolster TBy benefits are needed for men. PMID:27092271

  19. Barriers to access to antiretroviral treatment in Mozambique, as perceived by patients and health workers in urban and rural settings.

    PubMed

    Posse, Mariana; Baltussen, Rob

    2009-10-01

    This study identifies, ranks, and compares factors perceived as barriers to accessing antiretroviral treatment (ART) in urban and rural settings in Mozambique. Data were collected between March and July 2008. It consisted of 13 focus group discussions and a structured questionnaire administered to 252 people living with HIV/AIDS (PLWHA) and 28 health workers in the districts of Beira and Buzi. Data analysis was performed using content analysis, factor analysis, and percentages of the maximum attainable scores. The data analysis revealed six clusters of factors, which were ranked according to the percentages of the maximum attainable scores between brackets: (1) patient resource availability, in which distance from home to the health facility, transportation and food availability were rated below 40%; (2) community information (47%), and (3) service availability (53%), in which the waiting time to receive the results of CD4 analysis and the sufficiency of doctors/nurses at the health facility were both rated at 45%; (4) patient information and attitudes toward treatment (74%); family support (77%) and health personnel confidentiality (79%). Policy makers, in efforts to further improve the access to ART may decide to target their attention in designing interventions to improve specific aspects of patient resource availability, community information, and service availability in both urban and rural settings.

  20. Treatment Buddies Improve Clinic Attendance among Women but Not Men on Antiretroviral Therapy in the Nyanza Region of Kenya.

    PubMed

    Kibaara, Charles; Blat, Cinthia; Lewis-Kulzer, Jayne; Shade, Starley; Mbullo, Patrick; Cohen, Craig R; Bukusi, Elizabeth A

    2016-01-01

    Background. Kenyan antiretroviral (ART) guidelines encourage treatment buddies (TBy) to maximize treatment adherence. This study examined the effect of TBys on clinic attendance in men and women on ART. Methods. This retrospective cohort study included all adult patients initiating ART from August 2007 to December 2011 at four health facilities in Kenya. Data were abstracted from electronic medical records and analyzed using Poisson regression. Results. Of 2,430 patients, 2,199 (91%) had a TBy. Relationship between TBy and clinic attendance differed in females and males (interaction p = 0.09). After demographic and clinic factor adjustment, females with a TBy were 28% more likely to adhere to all appointments than those without (adjusted aRR = 1.28; 95% CI 1.08-1.53), whereas males were no more likely to adhere (aRR = 1.01; 95% CI 0.76-1.32). Males reported partner/spouse (33%) or brother (11%) as the TBy while females reported sister (17%), partner/spouse (14%), or another family member (12%). Multivariable analysis found no association between clinic attendance and TBy relationship in either gender. Conclusion. Clinic attendance was higher among women with TBys but not men. Results support TBys to help women achieve ART success; alternate strategies to bolster TBy benefits are needed for men.

  1. Temporal trends of time to antiretroviral treatment initiation, interruption and modification: examination of patients diagnosed with advanced HIV in Australia

    PubMed Central

    Wright, Stephen T; Law, Matthew G; Cooper, David A; Keen, Phillip; McDonald, Ann; Middleton, Melanie; Woolley, Ian; Kelly, Mark; Petoumenos, Kathy

    2015-01-01

    Introduction HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. Methods We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. Results Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural–regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007–2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007–2012 versus 1996–2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Conclusions Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods. PMID:25865372

  2. Evidence of improving antiretroviral therapy treatment delays: an analysis of eight years of programmatic outcomes in Blantyre, Malawi

    PubMed Central

    2013-01-01

    Background Impressive achievements have been made towards achieving universal coverage of antiretroviral therapy (ART) in sub-Saharan Africa. However, the effects of rapid ART scale-up on delays between HIV diagnosis and treatment initiation have not been well described. Methods A retrospective cohort study covering eight years of ART initiators (2004–2011) was conducted at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. The time between most recent positive HIV test and ART initiation was calculated and temporal trends in delay to initiation were described. Factors associated with time to initiation were investigated using multivariate regression analysis. Results From 2004–2011, there were 15,949 ART initiations at QECH (56% female; 8% children [0–10 years] and 5% adolescents [10–20 years]). Male initiators were likely to have more advanced HIV infection at initiation than female initiators (70% vs. 64% in WHO stage 3 or 4). Over the eight years studied, there were declines in treatment delay, with 2011 having the shortest delay at 36.5 days. On multivariate analysis CD4 count <50 cells/μl (adjusted geometric mean ratio [aGMR]: aGMR: 0.53, bias-corrected accelerated [BCA] 95% CI: 0.42-0.68) was associated with shorter ART treatment delay. Women (aGMR: 1.12, BCA 95% CI: 1.03-1.22) and patients diagnosed with HIV at another facility outside QECH (aGMR: 1.61, BCA 95% CI: 1.47-1.77) had significantly longer treatment delay. Conclusions Continued improvements in treatment delays provide evidence that universal access to ART can be achieved using the public health approach adopted by Malawi However, the longer delays for women and patients diagnosed at outlying sites emphasises the need for targeted interventions to support equitable access for these groups. PMID:23687946

  3. Cost estimates of HIV care and treatment with and without anti-retroviral therapy at Arba Minch Hospital in southern Ethiopia

    PubMed Central

    Bikilla, Asfaw Demissie; Jerene, Degu; Robberstad, Bjarne; Lindtjorn, Bernt

    2009-01-01

    Background Little is known about the costs of HIV care in Ethiopia. Objective To estimate the average per person year (PPY) cost of care for HIV patients with and without anti-retroviral therapy (ART) in a district hospital. Methods Data on costs and utilization of HIV-related services were taken from Arba Minch Hospital (AMH) in southern Ethiopia. Mean annual outpatient and inpatient costs and corresponding 95% confidence intervals (CI) were calculated. We adopted a district hospital perspective and focused on hospital costs. Findings PPY average (95% CI) costs under ART were US$235.44 (US$218.11–252.78) and US$29.44 (US$24.30–34.58) for outpatient and inpatient care, respectively. Estimates for the non-ART condition were US$38.12 (US$34.36–41.88) and US$80.88 (US$63.66–98.11) for outpatient and inpatient care, respectively. The major cost driver under the ART scheme was cost of ART drugs, whereas it was inpatient care and treatment in the non-ART scheme. Conclusion The cost profile of ART at a district hospital level may be useful in the planning and budgeting of implementing ART programs in Ethiopia. Further studies that focus on patient costs are warranted to capture all patterns of service use and relevant costs. Economic evaluations combining cost estimates with clinical outcomes would be useful for ranking of ART services. PMID:19364399

  4. The VACS Index Accurately Predicts Mortality and Treatment Response among Multi-Drug Resistant HIV Infected Patients Participating in the Options in Management with Antiretrovirals (OPTIMA) Study

    PubMed Central

    Brown, Sheldon T.; Tate, Janet P.; Kyriakides, Tassos C.; Kirkwood, Katherine A.; Holodniy, Mark; Goulet, Joseph L.; Angus, Brian J.; Cameron, D. William; Justice, Amy C.

    2014-01-01

    Objectives The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study. Methods Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel’s C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality. Results Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14–0.49) and 0.39(95% CI 0.22–0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27–3.38) and 1.51 (95%CI 0.90–2.53) for the 25% least improved scores. Conclusions The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research. PMID:24667813

  5. Generic antiretroviral drugs and HIV care: An economic review.

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures. PMID:26905394

  6. Generic antiretroviral drugs and HIV care: An economic review.

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures.

  7. Antiretroviral treatment regardless of CD4 count: the universal answer to a contextual question.

    PubMed

    Eholié, Serge P; Badje, Anani; Kouame, Gérard M; N'takpe, Jean-Baptiste; Moh, Raoul; Danel, Christine; Anglaret, Xavier

    2016-01-01

    After a period where it was recommended to start antiretroviral therapy (ART) early, the CD4 threshold for treating asymptomatic adults dropped to 200/mm(3) at the beginning of the 2000s. This was mostly due to a great prudence with regards to drug toxicity. The ART-start CD4 threshold in most international guidelines was then raised to 350/mm(3) in 2006-2009 and to 500/mm(3) in 2009-2013. Between 2012 and 2015, international guidelines went the last step further and recommended treating all HIV-infected adults regardless of their CD4 count. This ultimate step was justified by the results of three randomized controlled trials, HPTN 052, Temprano ANRS 12136 and START. These three trials assessed the benefits and risks of starting ART immediately upon inclusion ("early ART") versus deferring ART until the current starting criteria were met ("deferred ART"). Taken together, they recruited 8427 HIV-infected adults in 37 countries. The primary outcome was severe morbidity, a composite outcome that included all-cause deaths, AIDS diseases, and non-AIDS cancers in the three trials. The trial results were mutually consistent and reinforcing. The overall risk of severe morbidity was significantly 44-57 % lower in patients randomized to early ART as compared to deferred ART. Early ART also decreased the risk of AIDS, tuberculosis, invasive bacterial diseases and Kaposi's sarcoma considered separately. The incidence of severe morbidity was 3.2 and 3.5 times as high in HPTN052 and Temprano as in START, respectively. This difference is mostly due to the geographical context of morbidity. The evidence is now strong that initiating ART at high CD4 counts entails individual benefits worldwide, and that this is all the more true in low resource contexts where tuberculosis and other bacterial diseases are highly prevalent. These benefits in addition to population benefits consisting of preventing HIV transmission demonstrated in HPTN052, justify the recommendation that HIV

  8. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

    PubMed Central

    Spudich, Serena S; Nilsson, Annelie C; Lollo, Nicole D; Liegler, Teri J; Petropoulos, Christos J; Deeks, Steven G; Paxinos, Ellen E; Price, Richard W

    2005-01-01

    Background Central nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1) progression of systemic infection, 2) CSF white blood cell (WBC) count, 3) antiretroviral therapy (ART), and 4) neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL). CSF HIV viral loads (VLs) correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts <50 cells/μL associated with a low prevalence of CSF pleocytosis and large differences between plasma and CSF VL. CSF HIV RNA correlated neither with the severity of the AIDS dementia complex (ADC) nor abnormal quantitative neurological performance, although these measures were associated with depression of CD4 counts. In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression

  9. Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

    PubMed Central

    Labhardt, Niklaus Daniel; Keiser, Olivia; Sello, Motlalepula; Lejone, Thabo Ishmael; Pfeiffer, Karolin; Davies, Mary-Ann; Egger, Matthias; Ehmer, Jochen; Wandeler, Gilles

    2013-01-01

    Introduction Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73–1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93). Conclusions In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to

  10. Antiretroviral treatment regardless of CD4 count: the universal answer to a contextual question.

    PubMed

    Eholié, Serge P; Badje, Anani; Kouame, Gérard M; N'takpe, Jean-Baptiste; Moh, Raoul; Danel, Christine; Anglaret, Xavier

    2016-01-01

    After a period where it was recommended to start antiretroviral therapy (ART) early, the CD4 threshold for treating asymptomatic adults dropped to 200/mm(3) at the beginning of the 2000s. This was mostly due to a great prudence with regards to drug toxicity. The ART-start CD4 threshold in most international guidelines was then raised to 350/mm(3) in 2006-2009 and to 500/mm(3) in 2009-2013. Between 2012 and 2015, international guidelines went the last step further and recommended treating all HIV-infected adults regardless of their CD4 count. This ultimate step was justified by the results of three randomized controlled trials, HPTN 052, Temprano ANRS 12136 and START. These three trials assessed the benefits and risks of starting ART immediately upon inclusion ("early ART") versus deferring ART until the current starting criteria were met ("deferred ART"). Taken together, they recruited 8427 HIV-infected adults in 37 countries. The primary outcome was severe morbidity, a composite outcome that included all-cause deaths, AIDS diseases, and non-AIDS cancers in the three trials. The trial results were mutually consistent and reinforcing. The overall risk of severe morbidity was significantly 44-57 % lower in patients randomized to early ART as compared to deferred ART. Early ART also decreased the risk of AIDS, tuberculosis, invasive bacterial diseases and Kaposi's sarcoma considered separately. The incidence of severe morbidity was 3.2 and 3.5 times as high in HPTN052 and Temprano as in START, respectively. This difference is mostly due to the geographical context of morbidity. The evidence is now strong that initiating ART at high CD4 counts entails individual benefits worldwide, and that this is all the more true in low resource contexts where tuberculosis and other bacterial diseases are highly prevalent. These benefits in addition to population benefits consisting of preventing HIV transmission demonstrated in HPTN052, justify the recommendation that HIV

  11. Predictive factors of antiretroviral treatment <4 weeks among HIV-infected pregnant women in Cayenne, French Guiana.

    PubMed

    Elenga, Narcisse; Hanf, Matthieu; Nacher, Mathieu

    2012-01-01

    French Guiana is the French territory where the HIV epidemic is most preoccupying. In Cayenne, the mother to child HIV transmission rate was 6% in 2006-2008. Despite free testing and treatment, HIV pregnant women often have delayed or insufficient access to care. The aim of this study was to identify predictive factors of antiretroviral treatment<4 weeks in HIV pregnant women in Cayenne (French Guiana) and then to describe their attitudes, practices, and beliefs regarding HIV/AIDS. A case control study was conducted including all deliveries in Cayenne from 2003 to 2010. For each case, a standardized questionnaire including epidemiological, clinical, and biological data was administered. The analysis first described the summary statistics and then bivariate analysis studied the relation of each variable with the outcome. Multivariate analysis adjusted for the confounding factors. Thirty-three women in the first group and 96 in the control group were included in the study. Women born in French Guiana (OR = 5, IC95% = 1.22-20.86, p=0.027) had a high risk of treatment<4 weeks. The other factors associated with treatment<4 weeks in our study were benefiting from food parcels (OR = 12.72, IC95% = 2.07-78.14, p=0.006), consulting a traditional healer when sick (OR = 9.86, IC95% = 2.57-37.88, p= < 0.001), and drug use (OR = 6.27, IC95% = 1.26-31.13, p=0.025). These predictive factors should be considered in prevention programs against mother to child transmission of HIV.

  12. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    NASA Astrophysics Data System (ADS)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

  13. Antiretroviral treatment response of HIV-infected children after prevention of mother-to-child transmission in West Africa

    PubMed Central

    Ndondoki, Camille; Dicko, Fatoumata; Coffie, Patrick Ahuatchi; Eboua, Tanoh Kassi; Ekouevi, Didier Koumavi; Kouadio, Kouakou; Aka, Addi Edmond; Malateste, Karen; Dabis, François; Amani-Bosse, Clarisse; Toure, Pety; Leroy, Valériane

    2014-01-01

    Introduction We assessed the rate of treatment failure of HIV-infected children after 12 months on antiretroviral treatment (ART) in the Paediatric IeDEA West African Collaboration according to their perinatal exposure to antiretroviral drugs for preventing mother-to-child transmission (PMTCT). Methods A retrospective cohort study in children younger than five years at ART initiation between 2004 and 2009 was nested within the pWADA cohort, in Bamako-Mali and Abidjan-Côte d’Ivoire. Data on PMTCT exposure were collected through a direct review of children’s medical records. The 12-month Kaplan-Meier survival without treatment failure (clinical or immunological) was estimated and their baseline factors studied using a Cox model analysis. Clinical failure was defined as the appearance or reappearance of WHO clinical stage 3 or 4 events or any death occurring within the first 12 months of ART. Immunological failure was defined according to the 2006 World Health Organization age-related immunological thresholds for severe immunodeficiency. Results Among the 1035 eligible children, PMTCT exposure was only documented for 353 children (34.1%) and remained unknown for 682 (65.9%). Among children with a documented PMTCT exposure, 73 (20.7%) were PMTCT exposed, of whom 61.0% were initiated on a protease inhibitor-based regimen, and 280 (79.3%) were PMTCT unexposed. At 12 months on ART, the survival without treatment failure was 40.6% in the PMTCT-exposed group, 25.2% in the unexposed group and 18.5% in the children with unknown exposure status (p=0.002). In univariate analysis, treatment failure was significantly higher in children unexposed (HR 1.4; 95% CI: 1.0–1.9) and with unknown PMTCT exposure (HR 1.5; 95% CI: 1.2–2.1) rather than children PMTCT-exposed (p=0.01). In the adjusted analysis, treatment failure was not significantly associated with PMTCT exposure (p=0.15) but was associated with immunodeficiency (aHR 1.6; 95% CI: 1.4–1.9; p=0.001), AIDS clinical

  14. Risk of Deaths, AIDS-Defining and Non-AIDS Defining Events among Ghanaians on Long-Term Combination Antiretroviral Therapy

    PubMed Central

    Sarfo, Fred Stephen; Sarfo, Maame Anima; Norman, Betty; Phillips, Richard; Bedu-Addo, George; Chadwick, David

    2014-01-01

    Combination antiretroviral therapy (cART) has been widely available in Ghana since 2004. The aim of this cohort study was to assess the incidences of death, AIDS-defining events and non-AIDS defining events and associated risk factors amongst patients initiating cART in a large treatment centre. Clinical and laboratory data were extracted from clinic and hospital case notes for patients initiating cART between 2004 and 2010 and clinical events graded according to recognised definitions for AIDS, non-AIDS events (NADE) and death, with additional events not included in such definitions such as malaria also included. The cumulative incidence of events was calculated using Kaplan Meier analysis, and association of risk factors with events by Cox proportional hazards regression. Data were closed for analysis on 31st December, 2011 after a median follow-up of 30 months (range, 0–90 months). Amongst 4,039 patients starting cART at a median CD4 count of 133 cells/mm3, there were 324 (8%) confirmed deaths, with an event rate of 28.83 (95% CI 25.78–32.15) deaths per 1000-person follow-up years; the commonest established causes were pulmonary TB and gastroenteritis. There were 681 AIDS-defining events (60.60 [56.14–65.33] per 1000 person years) with pulmonary TB and chronic diarrhoea being the most frequent causes. Forty-one NADEs were recorded (3.64 [2.61–4.95] per 1000 person years), of which hepatic and cardiovascular events were most common. Other common events recorded outside these definitions included malaria (746 events) and respiratory tract infections (666 events). Overall 24% of patients were lost-to-follow-up. Alongside expected risk factors, stavudine use was associated with AIDS [adjusted HR of 1.08 (0.90–1.30)] and death (adjusted HR of 1.60 [1.21–2.11]). Whilst frequency of AIDS and deaths in this cohort were similar to those described in other sub-Saharan African cohorts, rates of NADEs were lower and far exceeded by events such as malaria and

  15. Risk of deaths, AIDS-defining and non-AIDS defining events among Ghanaians on long-term combination antiretroviral therapy.

    PubMed

    Sarfo, Fred Stephen; Sarfo, Maame Anima; Norman, Betty; Phillips, Richard; Bedu-Addo, George; Chadwick, David

    2014-01-01

    Combination antiretroviral therapy (cART) has been widely available in Ghana since 2004. The aim of this cohort study was to assess the incidences of death, AIDS-defining events and non-AIDS defining events and associated risk factors amongst patients initiating cART in a large treatment centre. Clinical and laboratory data were extracted from clinic and hospital case notes for patients initiating cART between 2004 and 2010 and clinical events graded according to recognised definitions for AIDS, non-AIDS events (NADE) and death, with additional events not included in such definitions such as malaria also included. The cumulative incidence of events was calculated using Kaplan Meier analysis, and association of risk factors with events by Cox proportional hazards regression. Data were closed for analysis on 31st December, 2011 after a median follow-up of 30 months (range, 0-90 months). Amongst 4,039 patients starting cART at a median CD4 count of 133 cells/mm3, there were 324 (8%) confirmed deaths, with an event rate of 28.83 (95% CI 25.78-32.15) deaths per 1000-person follow-up years; the commonest established causes were pulmonary TB and gastroenteritis. There were 681 AIDS-defining events (60.60 [56.14-65.33] per 1000 person years) with pulmonary TB and chronic diarrhoea being the most frequent causes. Forty-one NADEs were recorded (3.64 [2.61-4.95] per 1000 person years), of which hepatic and cardiovascular events were most common. Other common events recorded outside these definitions included malaria (746 events) and respiratory tract infections (666 events). Overall 24% of patients were lost-to-follow-up. Alongside expected risk factors, stavudine use was associated with AIDS [adjusted HR of 1.08 (0.90-1.30)] and death (adjusted HR of 1.60 [1.21-2.11]). Whilst frequency of AIDS and deaths in this cohort were similar to those described in other sub-Saharan African cohorts, rates of NADEs were lower and far exceeded by events such as malaria and respiratory

  16. Side effects, adherence self-efficacy, and adherence to antiretroviral treatment: a mediation analysis in a Chinese sample.

    PubMed

    Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita

    2016-07-01

    Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.

  17. Act local, think global: how the Malawi experience of scaling up antiretroviral treatment has informed global policy.

    PubMed

    Harries, Anthony D; Ford, Nathan; Jahn, Andreas; Schouten, Erik J; Libamba, Edwin; Chimbwandira, Frank; Maher, Dermot

    2016-01-01

    The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030. PMID:27600800

  18. Act local, think global: how the Malawi experience of scaling up antiretroviral treatment has informed global policy.

    PubMed

    Harries, Anthony D; Ford, Nathan; Jahn, Andreas; Schouten, Erik J; Libamba, Edwin; Chimbwandira, Frank; Maher, Dermot

    2016-01-01

    The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030.

  19. Intervening in global markets to improve access to HIV/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets

    PubMed Central

    2010-01-01

    Background Universal access to antiretroviral therapy (ART) in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV) medicines, limited financing, and few fixed-dose combination (FDC) products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions. Methods We utilize several data sources, including 12,958 donor-funded, adult first-line ARV purchase transactions, to describe the market from 2002-2008. We examine relationships between market trends and: World Health Organization (WHO) HIV/AIDS treatment guidelines; WHO Prequalification Programme (WHO Prequal) and United States (US) Food and Drug Administration (FDA) approvals; and procurement policies of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), US President's Emergency Plan for AIDS Relief (PEPFAR) and UNITAID. Results WHO recommended 7, 4, 24, and 6 first-line regimens in 2002, 2003, 2006 and 2009 guidelines, respectively. 2009 guidelines replaced a stavudine-based regimen ($88/person/year) with more expensive zidovudine- ($154-260/person/year) or tenofovir-based ($244-465/person/year) regimens. Purchase volumes for ARVs newly-recommended in 2006 (emtricitabine, tenofovir) increased >15-fold from 2006 to 2008. Twenty-four generic FDCs were quality-approved for older regimens but only four for newer regimens. Generic FDCs were available to GFATM recipients in 2004 but to PEPFAR recipients only after FDA approval in 2006. Price trends for single-component generic medicines mirrored generic FDC prices. Two large-scale purchasers, PEPFAR and UNITAID, together accounted for 53%, 84%, and 77% of market volume for abacavir, emtricitabine, and tenofovir, respectively, in 2008. PEPFAR and UNITAID purchases were often split across two manufacturers. Conclusions Global initiatives facilitated the

  20. Keeping kids in care: virological failure in a paediatric antiretroviral clinic and suggestions for improving treatment outcomes.

    PubMed

    Purchase, Susan; Cunningham, Jayne; Esser, Monika; Skinner, Donald

    2016-09-01

    The burden of paediatric HIV in South Africa is extremely high. Antiretrovirals (ARVs) are now widely accessible in the country and the clinical emphasis has shifted from initiation of treatment to retention in care. This study describes the cumulative virological failure rate amongst children on ARVs in a peri-urban clinic, and suggests ways in which clinics and partners could improve treatment outcomes. The study was conducted by the non-profit organisation HOPE Cape Town Association. A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all children with a viral load >1000 copies/ml, children on monotherapy, children who had stopped treatment, children lost to follow-up (LTFU) and children who had died. Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care. Cumulative virological failure rate was 42%, with most of those children having been LTFU. Both staff and caregivers consistently identified pharmacy queues, ongoing stigma and unpalatable ARVs as barriers to adherence. Staff suggestions included use of adherence aids, and better education and support groups for caregivers. Caregivers also requested support groups, as well as "same day" appointments for caregivers and children, but rejected the idea of home visits. Simple, acceptable and cost-effective strategies exist whereby clinics and their partners could significantly reduce the cumulative virological failure rate in paediatric ARV clinics. These include actively tracing defaulters, improving education, providing support groups, and campaigning for palatable ARV formulations. PMID:27681154

  1. Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

    PubMed

    Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

    2014-01-01

    A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

  2. Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

    PubMed

    Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

    2014-01-01

    A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment. PMID:25310645

  3. Dried plasma/blood spots for monitoring antiretroviral treatment efficacy and pharmacokinetics: a cross-sectional study in rural Burundi

    PubMed Central

    Calcagno, Andrea; Motta, Ilaria; Milia, Maria Grazia; Rostagno, Roberto; Simiele, Marco; Libanore, Valentina; Fontana, Silvia; D'Avolio, Antonio; Ghisetti, Valeria; Di Perri, Giovanni; Bonora, Stefano

    2015-01-01

    Aims In limited resource settings monitoring antiretroviral (ARV) treatment efficacy is restrained by the lack of access to technological equipment. The aim of the study was to assess the use of dried plasma (DPS) and blood spots (DBS) to facilitate ARV monitoring in remote settings where clinical monitoring is the primary strategy. Methods A cross-sectional study in HIV-positive ARV-treated patients in Kiremba, Burundi was performed. DBS were used for HIV-1 viral load (limit of the assay 250 copies ml−1) and genotypic drug resistance tests and dried plasma spots were used for concentration measurements. Results Three hundred and seven patients [201 female (88.6%), 14 children (4.5%)] were enrolled. HIV-1 viral load was <250, 250–1000 and >1000 copies ml−1 in 250 (81.7%), 33 (10.8%) and 23 patients (7.5%). Eleven samples out of 23 were successfully amplified revealing nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistance associated mutations [in seven (58.3%) and six patients (50%)]. Nevirapine trough concentrations were <3000 ng ml−1 in 28/189 patients (14.8%) and efavirenz 12 h concentrations were <1000 ng ml−1 in 2/16 patients (12.5%). Children and patients with nevirapine exposure <3000 ng ml−1 presented a higher risk of viral replication. Conclusions Viral loads <250 copies ml−1 were observed in 81.7% of patients (83.6% adults and 42.9% children). Children and patients with low nevirapine concentrations had higher risk of viral replication. Dried blood and plasma spots may be useful for monitoring HIV-positive patients including viral load and drug level measurement as part of treatment management in remote areas. PMID:25377591

  4. "They are looking just the same": Antiretroviral treatment as social danger in rural Malawi.

    PubMed

    Kaler, Amy; Angotti, Nicole; Ramaiya, Astha

    2016-10-01

    Research on the social impact of ART pivots on questions of individual adherence and community acceptability of treatment programmes. In this paper we examine unexpected and unintended consequences of the scale-up of treatment in rural Malawi, using a unique dataset of more than 150 observational journals from three sites, spanning 2010 to 2013, focusing on men's everyday conversations. Through thematic content analysis, we explore the emerging perception that the widespread availability of ART constitutes a form of social danger, as treatment makes it difficult to tell who does or does not have AIDS. This ambiguity introduced through ART is interpreted as putting individuals at risk, because it is no longer possible to tell who might be infected - indeed, the sick now look healthier and "plumper" than the well. This ambivalence over the social impact of ART co-exists with individual demand for and appreciation of the benefits of treatment.

  5. Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir

    PubMed Central

    Brown, Todd T.; Moser, Carlee; Currier, Judith S.; Ribaudo, Heather J.; Rothenberg, Jennifer; Kelesidis, Theodoros; Yang, Otto; Dubé, Michael P.; Murphy, Robert L.; Stein, James H.; McComsey, Grace A.

    2015-01-01

    Background. Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART initiation. Methods. We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss. Results. At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: −4.0% in the ATV/r group vs −3.6% in the DRV/r [P = .42]; hip: −3.9% in the ATV/r group vs −3.4% in the DRV/r group [P = .36]) but were greater in the combined PI arms than in the RAL arm (spine: −3.8% vs −1.8% [P < .001]; hip: −3.7% vs −2.4% [P = .005]). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4+ T-cell senescence and exhaustion (CD4+CD28−CD57+PD1+) and CD4+ T-cell activation (CD4+CD38+HLA-DR+) were associated with lumbar spine BMD loss. Conclusions. BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss. PMID:25948863

  6. Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4+ T-Cell Activation in Patients Coinfected With HIV and Hepatitis C Virus and Receiving Antiretroviral Therapy.

    PubMed

    Morón-López, Sara; Gómez-Mora, Elisabet; Salgado, Maria; Ouchi, Dan; Puertas, Maria C; Urrea, Víctor; Navarro, Jordi; Jou, Antoni; Pérez, Mercedes; Tural, Cristina; Clotet, Bonaventura; Montaner, Luis J; Blanco, Julià; Crespo, Manuel; Martinez-Picado, Javier

    2016-03-15

    Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4(+) T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2-long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation. PMID:26525407

  7. Combined photoultrasonic treatment of infected wounds

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.; Menyaev, Yulian A.; Kalinin, Konstantin L.; Zmievskoy, Gregory N.; Velsher, Leonid Z.; Podkolzin, Alexander A.; Stakhanov, Mikhail L.; Gorchak, Yury Y.; Sarantsev, V. P.

    2001-05-01

    A new combined photoultrasonic (CPUS) technology for the treatment of infected wounds is suggested. The CPUS principal operation is based on the topical application of a photosensitizer followed by light irradiation in combination with low frequency ultrasonic (US) treatment of wounds. In CPUS, two methods - photodynamic (PDT) and ultrasonic therapies supplement each other beneficially and in conjunction provide a significant effect of deep suppurative inflammatory wounds treatment. The main advantages of the new technology are the combined application of an antibiotic solution and photodynamic therapy to destroy antibiotic- resistant microorganisms, an effective mixing of a photosensitizer in the wound, the US enhancement of photosensitizer impregnation into the membranes of bacteria, the US clearing of wound surface from necrotic products, an increased effective light dose exposure in the whole volume of the deep wound when the light does not penetrate totally inside the wound, an additional bactericidal effect under the US impact, and the combined effect of CPUS activation of the immune system.

  8. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

    Vadlapatla, Ramya Krishna; Patel, Mitesh; Paturi, Durga K; Pal, Dhananjay; Mitra, Ashim K

    2015-01-01

    Introduction Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide. Areas covered Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations. Expert opinion Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echino-candins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections. PMID:24521092

  9. Pain Treatment and Antiretroviral Medication Adherence Among Vulnerable HIV-Positive Patients

    PubMed Central

    Kurtz, Steven P.; Levi-Minzi, Maria A.; Cicero, Theodore J.; Tsuyuki, Kiyomi; O'Grady, Catherine L.

    2015-01-01

    Abstract Pain represents a significant source of morbidity, function loss, and decreased quality of life among people living with HIV. The present study examined the associations among pain, pain treatment, and ARV adherence among indigent, HIV-positive substance abusers. Participants were recruited via targeted sampling strategies, and completed a one-time computer-assisted personal interview. ANOVA and chi-square tests were used to analyze differences in demographics, health and psychological status, health behaviors, by pain and pain treatment status; a multivariate logistic regression model was constructed to examine the contribution of pain/treatment status to recent ARV adherence. Results indicated that those with untreated pain had lower odds of achieving gold-standard 95% ARV adherence as compared to the pain-free and treated pain groups; higher substance dependence symptoms were also associated with significantly lower odds of 95% ARV adherence. Findings suggest that pain management is critical to the health of people living with HIV, specifically those with high levels of co-morbid health and psychological problems. The prevalence of untreated pain was elevated among this group, and contributed to reduced ARV adherence. Providers of clinical care to disadvantaged HIV-positive patients should emphasize routine assessment and appropriate treatment of pain in order to provide comprehensive HIV care. PMID:24984142

  10. Antiretrovirals for developing world.

    PubMed

    Adler, M W

    1998-01-24

    The most recent UNAIDS figures indicate that approximately 30 million people are infected with HIV worldwide, 5.8 million of whom were newly infected during 1997. At the 10th International Conference on AIDS and Sexually Transmitted Diseases in Africa, the President and Secretary of Health of France called upon developed countries to establish a Therapeutic Assistance Fund to make antiretrovirals available to people with HIV/AIDS in sub-Saharan Africa. While the annual per capita health budget in most African countries is less than US$10, triple antiretroviral therapy against AIDS in the developed world costs $12,000-14,000 per patient per year. Calculations based upon a lower per patient cost of $7000, and treating all 1.4 million African AIDS cases, would cost US$10 billion per year for drugs alone, more than 30 times the amount currently spent annually by international donors for AIDS programs in the entire developing world. Basic infrastructural requirements would have to be met were antiretrovirals made widely available, ranging from HIV screening and counseling to the provision of clean water with which to consume the required 20-30 tablets per day. High program costs will challenge long-term sustainability. Universal access to care and treatment for HIV infection and AIDS is not a reality in the developed world, let alone feasible in developing countries. Given the competing health care priorities in developing countries, the high costs of antiretroviral agents, poor infrastructure, and inability to sustain such a program, the French initiative is ill-advised and foolish public health practice.

  11. The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.

    PubMed

    Outlaw, Angulique Y; Naar-King, Sylvie; Tanney, Mary; Belzer, Marvin E; Aagenes, Anna; Parsons, Jeffrey T; Merlo, Lisa J

    2014-01-01

    Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study.

  12. The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.

    PubMed

    Outlaw, Angulique Y; Naar-King, Sylvie; Tanney, Mary; Belzer, Marvin E; Aagenes, Anna; Parsons, Jeffrey T; Merlo, Lisa J

    2014-01-01

    Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study. PMID:23869650

  13. Toward universal access to HIV counseling and testing and antiretroviral treatment in Ethiopia: looking beyond HIV testing and ART initiation.

    PubMed

    Assefa, Yibeltal; Van Damme, Wim; Mariam, Damen Haile; Kloos, Helmut

    2010-08-01

    Expanding access to HIV counseling and testing (HCT) and antiretroviral treatment (ART) has reduced morbidity and mortality in people living with HIV/AIDS. As a result, many countries are scaling up HIV/AIDS services. In this paper we discuss challenges experienced during the move toward universal access to HCT and ART services in Ethiopia. We reviewed routine reports from the Ministry of Health and implementing partners. We also had interviews, about linkage to and retention in care of patients, with 10 HIV/AIDS program managers, as well as 2 to 7 health care providers and 5 to 15 patients in each of 23 health centers and 32 hospitals in all regions of the country. We found that the number of people tested for HIV increased 10-fold from 435,854 in 2005 to 4,559,954 in 2008. Only 61% of the HIV-positive patients were linked to chronic care immediately after tested for HIV. The number of patients initiated on ART annually increased from 26,021 in 2005 to 53,696 in 2008. Attrition of patients increased from 18% in 2005 to 26% in 2008. Our interviews indicated that fear of stigma, transport cost, feeling healthy and opting for traditional medicines were the main reasons for poor linkage to and retention in care. Lack of nutrition and feeling better were also reasons for poor retention. In conclusion, in spite of the rapid scale-up of HCT and ART services in Ethiopia, linkage and retention were not adequate. Therefore, strategies should be developed and implemented to improve linkage and retention.

  14. Delayed antiretroviral therapy despite integrated treatment for tuberculosis and human immunodeficiency virus

    PubMed Central

    Patel, Monita R.; Nana, Mbonze; Yotebieng, Marcel; Tabala, Martine; Behets, Frieda; Van Rie, Annelies

    2016-01-01

    Setting Five primary health care clinics in Kinshasa, Democratic Republic of Congo. Objective To examine timing and predictors of delayed ART initiation during TB treatment. Design Prospective observational cohort of adult patients receiving integrated TB/HIV treatment, expected to initiate ART at 1 month if CD4 count <100 cells/mm3 or WHO clinical stage 4 for reason other than extrapulmonary TB, at 2 months if CD4 count 100–350 cells/mm3, or at completion of TB treatment if subsequently CD4 count ≤350 cells/mm3 or WHO clinical stage 4. Results Of 492 patients, 235 (47.8%) experienced delayed ART initiation: 171 (72.8%) initiated ART late, after a median delay of 12 days (IQR 4–27) and 64 (27.2%) never initiated ART. Contraindication to any ARV drug (adjOR 2.91, 95% CI 1.22–6.95), lower baseline CD4 count (adjOR 1.20, 95% CI 1.08–1.33 per 100 cells/mm3), TB drug intolerance (adjOR 1.93, 95% CI 1.23–3.02), and non-disclosure of HIV-infection (adjOR 1.50, 95% CI 1.03–2.18) predicted delayed ART initiation. Conclusion Despite fully-integrated treatment, half of all patients experienced delayed ART initiation. Pragmatic approaches to ensure timely ART initiation in those at-risk of delayed ART initiation are needed. PMID:24903941

  15. Clinical implications of resistance to antiretroviral drugs.

    PubMed

    Vella, S

    1997-06-01

    New virological concepts are emerging and results from trials using potent combinations have demonstrated that drug resistance in AIDS therapy can be delayed, if not completely overcome, by appropriate treatment strategies. The definition and measures of resistance are explained, including the general mechanisms of resistance. Resistance patterns with nucleoside analogues, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors are examined, followed by a discussion of the clinical implications. It is suggested that, based on HIV-1 replication in vivo, early and aggressive antiretroviral therapy is needed to minimize the negative consequences of its replication. Recommended clinical guidelines for avoiding drug resistance are listed. PMID:11364354

  16. Predictors of loss to follow-up in antiretroviral treatment for adult patients in the Oromia region, Ethiopia

    PubMed Central

    Megerso, Abebe; Garoma, Sileshi; Eticha, Tolosa; Workineh, Tilaye; Daba, Shallo; Tarekegn, Mihretu; Habtamu, Zelalem

    2016-01-01

    Purpose It is known that antiretroviral treatment (ART) reduces mortality from acquired immunodeficiency syndrome related causes. Patient’s lost to follow-up (LTFU) in this treatment poses a paramount problem to the public and health care services. Information on predictors of loss to follow-up is scarce in this study area and similar settings. Therefore, this study aimed at identifying correlates of loss to follow-up in ART among adult patients in the Oromia region of Ethiopia. Methods A case–control study was conducted between February 2015 and April 2015 using medical records. The stratified sampling technique was used to select health facilities. The number of patient records to be included in the study was proportionally allocated to each stratum based on their patient proportion in the regional data. Specific health facilities from which to include the records were randomly selected from a list of the health facilities per stratum. All adult patient records registered as LTFU (416) in the selected health facilities during the 12-month period prior to the data collection date, and 832 patients with good adherence to ART were included. Data were double-entered into Epi Info 7 and analyzed using SPSS 20. Descriptive statistics and binary logistic regression were used to report the results. Qualitative data were thematically analyzed using open code computer software. Results Age 15–24 years (adjusted odds ratio [AOR], 19.82 95% CI: 6.80, 57.73); day laborers (AOR, 5.36; 95% confidence interval [CI]: 3.23, 8.89), rural residents (AOR, 2.35; 95% CI: 1.45, 3.89), World Health Organization clinical stage IV (AOR, 2.29; 95% CI: 1.45, 3.62), baseline CD4 <350 cells/mL (AOR, 2.06; 95% CI: 1.36, 3.13), suboptimal adherence to ART (AOR, 7.42; 95% CI: 1.87, 29.41), were factors which increased the risk of loss to follow-up in ART. Conclusion Multiple risk factors, both socioeconomic and clinical, were associated with loss to follow-up. Attention is required to

  17. A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa

    PubMed Central

    2011-01-01

    Background To better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts. Methods Surveys were conducted in April 2009. Analysis data from the Asia cohort were collected in March 2009 from 12 centres in Cambodia, India, Indonesia, Malaysia, and Thailand. Data from the IeDEA Southern Africa cohort were finalized in February 2008 from 10 centres in Malawi, Mozambique, South Africa and Zimbabwe. Results Survey responses reflected inter-regional variations in drug access and national guidelines. A total of 1301 children in the TREAT Asia and 4561 children in the IeDEA Southern Africa cohorts met inclusion criteria for the cross-sectional analysis. Ten percent of Asian and 3.3% of African children were on second-line ART at the time of data transfer. Median age (interquartile range) in months at second-line initiation was 120 (78-145) months in the Asian cohort and 66 (29-112) months in the southern African cohort. Regimens varied, and the then current World Health Organization-recommended nucleoside reverse transcriptase combination of abacavir and didanosine was used in less than 5% of children in each region. Conclusions In order to provide life-long ART for children, better use of current first-line regimens and broader access to heat-stable, paediatric second-line and salvage formulations are needed. There will be limited benefit to earlier diagnosis of treatment failure unless providers and patients have access to appropriate drugs for children to switch to. PMID:21306608

  18. Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana.

    PubMed

    Martinez, S S; Campa, A; Bussmann, H; Moyo, S; Makhema, J; Huffman, F G; Williams, O D; Essex, M; Marlink, R; Baum, M K

    2016-06-01

    An obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0-24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression. PMID:27087233

  19. Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana.

    PubMed

    Martinez, S S; Campa, A; Bussmann, H; Moyo, S; Makhema, J; Huffman, F G; Williams, O D; Essex, M; Marlink, R; Baum, M K

    2016-06-01

    An obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0-24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression.

  20. Brief Report: Apparent Antiretroviral Overadherence by Pill Count is Associated With HIV Treatment Failure in Adolescents.

    PubMed

    Okatch, Harriet; Beiter, Kaylin; Eby, Jessica; Chapman, Jennifer; Marukutira, Tafireyi; Tshume, Ontibile; Matshaba, Mogomotsi; Anabwani, Gabriel M; Gross, Robert; Lowenthal, Elizabeth

    2016-08-15

    Pill counts with calculated adherence percentages are used in many settings to monitor adherence, but can be undermined by patients discarding pills to hide nonadherence. Pill counts suggesting that >100% of prescribed doses were taken can signal "pill dumping." We defined "overadherence" among a cohort of 300 HIV-infected adolescents as having greater than one-third of pill counts with >100% adherence during a year of follow-up. Apparent overadherence was more common in those with virologic failure than in those with suppressed viral loads (33% vs 13%, χ P = 0.001). Pill count adherence repeatedly >100% may identify HIV-infected adolescents at increased risk of treatment failure. PMID:26990822

  1. Combined treatment in punctate inner choroidopathy

    PubMed Central

    Terelak-Borys, Barbara; Zagajewska, Katarzyna; Jankowska-Lech, Irmina; Tesla, Piotr; Grabska-Liberek, Iwona

    2016-01-01

    Purpose The purpose of this study was to describe a combination treatment for choroidal neovascular (CNV) membrane, secondary to punctate inner choroidopathy (PIC). Patient and methods A 44-year-old female patient was diagnosed with PIC complicated by the development of recurrent juxtafoveal neovascular membrane. The treatment included a sequence of monotherapy regimens: systemic steroid therapy, photodynamic therapy, and intravitreal injections of vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF). Owing to the CNV membrane resistance to various types of monotherapy, a combination treatment consisting of local injections of steroid underneath the Tenon’s capsule and intravitreal anti-VEGF injections was used. Results Systemic steroid therapy resulted in rapid local improvement with a very short remission period. No positive effects of photodynamic therapy were observed. Sequential anti-VEGF injections led to remission periods of several months. Permanent regression of CNV membrane was achieved following combined local application of steroid and intravitreal anti-VEGF injections. Conclusion A combination treatment including steroid and anti-VEGF medication characterized by anti-inflammatory and antiangiogenic effects may be a very beneficial option for the treatment of recurrent CNV membrane as a complication of PIC. PMID:27729795

  2. Plasma and cerebrospinal fluid biomarkers predict cerebral injury in HIV-infected individuals on stable combination antiretroviral therapy

    PubMed Central

    Anderson, Albert M.; Harezlak, Jaroslaw; Bharti, Ajay; Mi, Deming; Taylor, Michael J.; Daar, Eric S.; Schifitto, Giovanni; Zhong, Jianhui; Alger, Jeffry R.; Brown, Mark S.; Singer, Elyse J.; Campbell, Thomas B.; McMahon, Deborah D.; Buchthal, Steven; Cohen, Ronald; Yiannoutsos, Constantin; Letendre, Scott L.; Navia, Bradford A.

    2015-01-01

    Objectives HIV-associated brain injury persists despite antiretroviral therapy (cART), but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy (MRS) in chronically HIV-infected subjects. Methods Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate+Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Predictive models were built via linear regression and the best models were chosen using the Akaike Information Criterion. Results Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG while metabolite changes in the FWM for NAA/Cr, GlxCr and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the three models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and MRS metabolites. Conclusions Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region dependent manner in chronically HIV-infected patients on stable cART. PMID:25622053

  3. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C–Coinfected Persons

    PubMed Central

    Brunet, Laurence; Moodie, Erica E. M.; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Klein, Marina B.

    2016-01-01

    Background. Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Methods. Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction–positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. Results. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, −3%, 19%) or NNRTI users (3% per 5 years, 95% CI, −7%, 12%). Conclusions. Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV–coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used. PMID:26400998

  4. Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

    PubMed Central

    Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

    2006-01-01

    OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

  5. [Combination treatment of hypertension in 2015].

    PubMed

    Špinar, Jindřich; Vítovec, Jiří; Špinarová, Lenka; Bendová, Miroslava

    2015-05-01

    We present an overview of the present views on combination treatment and on fixed combinations in the treatment of hypertension according to guidelines of ESH/ESC and ČSH from 2013. The most frequently recommended dual combinations include a blocker of the renin-angiotensin system (ACEI or sartan) and a calcium channel blocker, and further a blocker of the renin-angiotensin system and a diuretic and a calcium channel blocker and a diuretic. In 2014 a fixed-dose combination of an ACE inhibitor (perindopril), a calcium channel blocker (amlodipine) and an diuretic (indapamide) appeared on the Czech market. Within the PIANIST study including 4 731 insufficiently controlled hypertensives, a fixed-dose triple combination of perindopril, amlodipine and indapamide led to a decrease in blood pressure by 28.3/13.8 mm Hg and to a sufficient control of hypertension in 92 % of patients. The advantage of fixed combinations primarily consists in greater compliance of patients and thereby in a better control of hypertension. About 1/3 of hypertensives need a triple combination for a satisfactory blood pressure control. PMID:26075856

  6. Proactive coping and spirituality among patients who left or remained in antiretroviral treatment in St Petersburg, Russian Federation.

    PubMed

    Pecoraro, Anna; Pacciolla, Aureliano; O'Cleirigh, Conall; Mimiaga, Matthew; Kwiatek, Piotr; Blokhina, Elena; Verbitskaya, Elena; Krupitsky, Evgeny; Woody, George E

    2016-01-01

    Positive Psychology, the study of "positive" factors or strengths and evidence-based interventions to increase them, is a rapidly developing field that is beginning to be applied to HIV care. Proactive coping and spirituality are two positive characteristics that have been examined in multiple chronic serious health conditions. In the present study, lost-to-care (LTCs; did not attend treatment for ≥12 months; n = 120) and engaged-in-care HIV clinic patients (EICs; attended treatment for ≥12 months and adherent with antiretrovirals; n = 120) in Leningrad Oblast, Russian Federation were compared on the Proactive Coping Inventory and View of God Scale. EICs had higher scores in proactive coping [t(229) = 3.69; p = .001] and instrumental [t(232) = 2.17; p = .03] and emotional [t(233) = 2.33; p = .02] support, indicating that they engage in autonomous goal setting and self-regulate their thoughts and behaviors; obtain advice and support from their social network; and cope with emotional distress by turning to others. LTCs had higher scores in avoidance coping [t(236) = -2.31; p = .02]. More EICs were spiritual, religious, or both [ χ(2)(1, N = 239) = 7.49, p = .006]. EICs were more likely to believe in God/Higher Power [χ(2)(1, N = 239 = 8.89, p = .002] and an afterlife [ χ(2)(1, N = 236) = 5.11, p = .024]; have a relationship with God/Higher Power [ χ(2)(1, N = 237) = 12.76, p = .000]; and call on God/Higher Power for help, healing, or protection [ χ(2)(1, N = 239) = 9.61]. EICs had more positive [t(238) = 2.78; p = .006] and less negative [t(236) = -2.38; p = .002] views of God. Similar proportions, but slightly more EICs than LTCs were members of a faith community; members of a12-step group; or attended religious or spiritual services, meetings, or activities. More EICs than LTCs engaged in private spiritual or religious activities, such as

  7. Improved long-term antiretroviral treatment outcomes amongst patients receiving community-based adherence support in South Africa.

    PubMed

    Fatti, Geoffrey; Mothibi, Eula; Shaikh, Najma; Grimwood, Ashraf

    2016-11-01

    Retaining high levels of patients in care who are virally suppressed over long treatment periods has been an important challenge for antiretroviral treatment (ART) programmes in sub-Saharan Africa, the region having the highest HIV burden globally. Clinic-linked community-based adherence support (CBAS) programmes provide home-based adherence and psychosocial support for ART patients. However, there is little evidence of their longer-term impact. This study assessed the effectiveness of CBAS after eight years of ART. CBAS workers are lay healthcare personnel providing regular adherence and psychosocial support for ART patients and their households through home visits addressing household challenges affecting adherence. A multicentre cohort study using routinely collected data was undertaken at six public ART sites in a high HIV-prevalence South African district. Patient retention, loss to follow-up (LTFU), viral suppression and CD4 cell restoration were compared between patients with and without CBAS, using competing-risks regression, linear mixed models and log-binomial regression. 3861 patients were included, of whom 1616 (41.9%) received CBAS. Over 14,792 patient-years of observation, the cumulative incidence of LTFU was 37.3% and 46.2% amongst patients with and without CBAS, respectively, following 8 years of ART; adjusted subhazard ratio (CBAS vs. no CBAS) = 0.74 (95% CI: 0.66-0.84; P < .0001). Amongst patients on ART for 6.5-8 years, proportions not achieving viral suppression were 11.4% and 19.4% in patients with and without CBAS, respectively; adjusted risk ratio = 0.47 (95% CI: 0.26-0.86; P = .015). Annual CD4 cell increases from baseline were 62.8 cells/µL/year and 51.5 cells/µL/year amongst patients with and without CBAS, respectively, after 6.5 years or more (P = .034). After adjustment, annual CD4 cell recovery was 15.1 cells/µL/year (95% CI: 2.7-27.6) greater in CBAS patients (P = .017). ART patients who received CBAS had

  8. Proactive coping and spirituality among patients who left or remained in antiretroviral treatment in St Petersburg, Russian Federation.

    PubMed

    Pecoraro, Anna; Pacciolla, Aureliano; O'Cleirigh, Conall; Mimiaga, Matthew; Kwiatek, Piotr; Blokhina, Elena; Verbitskaya, Elena; Krupitsky, Evgeny; Woody, George E

    2016-01-01

    Positive Psychology, the study of "positive" factors or strengths and evidence-based interventions to increase them, is a rapidly developing field that is beginning to be applied to HIV care. Proactive coping and spirituality are two positive characteristics that have been examined in multiple chronic serious health conditions. In the present study, lost-to-care (LTCs; did not attend treatment for ≥12 months; n = 120) and engaged-in-care HIV clinic patients (EICs; attended treatment for ≥12 months and adherent with antiretrovirals; n = 120) in Leningrad Oblast, Russian Federation were compared on the Proactive Coping Inventory and View of God Scale. EICs had higher scores in proactive coping [t(229) = 3.69; p = .001] and instrumental [t(232) = 2.17; p = .03] and emotional [t(233) = 2.33; p = .02] support, indicating that they engage in autonomous goal setting and self-regulate their thoughts and behaviors; obtain advice and support from their social network; and cope with emotional distress by turning to others. LTCs had higher scores in avoidance coping [t(236) = -2.31; p = .02]. More EICs were spiritual, religious, or both [ χ(2)(1, N = 239) = 7.49, p = .006]. EICs were more likely to believe in God/Higher Power [χ(2)(1, N = 239 = 8.89, p = .002] and an afterlife [ χ(2)(1, N = 236) = 5.11, p = .024]; have a relationship with God/Higher Power [ χ(2)(1, N = 237) = 12.76, p = .000]; and call on God/Higher Power for help, healing, or protection [ χ(2)(1, N = 239) = 9.61]. EICs had more positive [t(238) = 2.78; p = .006] and less negative [t(236) = -2.38; p = .002] views of God. Similar proportions, but slightly more EICs than LTCs were members of a faith community; members of a12-step group; or attended religious or spiritual services, meetings, or activities. More EICs than LTCs engaged in private spiritual or religious activities, such as

  9. Understanding reasons for treatment interruption amongst patients on antiretroviral therapy – A qualitative study at the Lighthouse Clinic, Lilongwe, Malawi

    PubMed Central

    Tabatabai, Julia; Namakhoma, Ireen; Tweya, Hannock; Phiri, Sam; Schnitzler, Paul; Neuhann, Florian

    2014-01-01

    Background In recent years, scaling up of antiretroviral therapy (ART) in resource-limited settings moved impressively towards universal access. Along with these achievements, public health HIV programs are facing a number of challenges including the support of patients on lifelong therapy and the prevention of temporary/permanent loss of patients in care. Understanding reasons for treatment interruption (TI) can inform strategies for improving drug adherence and retention in care. Objective To evaluate key characteristics of patients resuming ART after TI at the Lighthouse Clinic in Lilongwe, Malawi, and to identify their reasons for interrupting ART. Design This study uses a mixed methods design to evaluate patients resuming ART after TI. We analysed an assessment form for patients with TI using pre-defined categories and a comments field to identify frequently stated reasons for TI. Additionally, we conducted 26 in-depth interviews to deepen our understanding of common reasons for TI. In-depth interviews also included the patients’ knowledge about ART and presence of social support systems. Qualitative data analysis was based on a thematic framework approach. Results A total of 347 patients (58.2% female, average age 35.1±11.3 years) with TI were identified. Despite the presence of social support and sufficient knowledge of possible consequences of TI, all patients experienced situations that resulted in TI. Analysis of in-depth interviews led to new and distinct categories for TI. The most common reason for TI was travel (54.5%, n=80/147), which further differentiated into work- or family-related travel. Patients also stated transport costs and health-care-provider-related reasons, which included perceived/enacted discrimination by health care workers. Other drivers of TI were treatment fatigue/forgetfulness, the patients’ health status, adverse drug effects, pregnancy/delivery, religious belief or perceived/enacted stigma. Conclusions To adequately

  10. Virologic and Immunologic Correlates With the Magnitude of Antibody Responses to the Hepatitis A Vaccine in HIV-Infected Children on Highly Active Antiretroviral Treatment

    PubMed Central

    Weinberg, Adriana; Huang, Sharon; Fenton, Terence; Patterson-Bartlett, Julie; Gona, Philimon; Read, Jennifer S.; Dankner, Wayne M.; Nachman, Sharon

    2010-01-01

    Background HIV-infected individuals mount poor antibody responses to vaccines. We sought to identify the immunologic and virologic factors associated with a robust response to hepatitis Avirus (HAV) vaccine in children on highly active antiretroviral treatment. Methods One hundred fifty-two pediatric highly active antiretroviral treatment recipients immunized against HAV at weeks 0 and 24 had anti-HAV antibodies, CD4+, CD8+, and CD19+ cell percent assessed at weeks 0 and 32. Subgroups had HIV viremia, B- and T-cell subpopulations, and cell-mediated immunity (CMI) to HAV and other stimulants measured. Results Anti-HAV antibodies after complete vaccination correlated positively with CD4+ percent and CD19+ percent and negatively with viremia and CD8+ percent at baseline, but not at 32 weeks. There were no significant correlations between anti-HAV antibodies and B- or T-cell-naïve, memory, or activated subpopulations or non-HAV CMI. Compared with children who remained HAV-CMI-negative, those who mounted HAV-CMI in response to vaccination had higher anti-HAV antibody titers and CD19+ CD21+ CD27+ memory B cell percent at 32 weeks, but no other differences. Conclusions In HIV-infected children on highly active antiretroviral treatment, control of viral replication and conserved or reconstituted CD19+ and CD4+ cell numbers and function determine a robust antibody response to anti-HAV primary immunization. Our data support a bidirectional B- and T-cell cooperation in the response to the HAV vaccine. PMID:19617848

  11. Alarming rates of virological failure and drug resistance in patients on long-term antiretroviral treatment in routine HIV clinics in Togo.

    PubMed

    Konou, Abla A; Dagnra, Anoumou Y; Vidal, Nicole; Salou, Mounerou; Adam, Zakillatou; Singo-Tokofai, Assétina; Delaporte, Eric; Prince-David, Mireille; Peeters, Martine

    2015-11-28

    Information on efficacy of long-term antiretroviral treatment (ART) exposure in resource-limited countries is still scarce. In 767 patients attending routine HIV centers in Togo and receiving first-line ART for more than four years, 42% had viral load greater than 1000 copies/ml and either were on a completely ineffective ART regime or were with only a single drug active. The actual conditions to ensure lifelong ART in resource-limited countries can have dramatic long-term outcomes. PMID:26558549

  12. Alarming rates of virological failure and drug resistance in patients on long-term antiretroviral treatment in routine HIV clinics in Togo.

    PubMed

    Konou, Abla A; Dagnra, Anoumou Y; Vidal, Nicole; Salou, Mounerou; Adam, Zakillatou; Singo-Tokofai, Assétina; Delaporte, Eric; Prince-David, Mireille; Peeters, Martine

    2015-11-28

    Information on efficacy of long-term antiretroviral treatment (ART) exposure in resource-limited countries is still scarce. In 767 patients attending routine HIV centers in Togo and receiving first-line ART for more than four years, 42% had viral load greater than 1000 copies/ml and either were on a completely ineffective ART regime or were with only a single drug active. The actual conditions to ensure lifelong ART in resource-limited countries can have dramatic long-term outcomes.

  13. Evaluation of Combinations of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine with Clinically Used Antiretroviral Drugs

    PubMed Central

    Hachiya, Atsuko; Reeve, Aaron B.; Marchand, Bruno; Michailidis, Eleftherios; Ong, Yee Tsuey; Kirby, Karen A.; Leslie, Maxwell D.; Oka, Shinichi; Kodama, Eiichi N.; Rohan, Lisa C.; Mitsuya, Hiroaki; Parniak, Michael A.

    2013-01-01

    Drug combination studies of 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) with FDA-approved drugs were evaluated by two different methods, MacSynergy II and CalcuSyn. Most of the combinations, including the combination of the two adenosine analogs EFdA and tenofovir, were essentially additive, without substantial antagonism or synergism. The combination of EFdA and rilpivirine showed apparent synergism. These studies provide information that may be useful for the design of EFdA combination regimens for initial and salvage therapy assessment. PMID:23796932

  14. Antiretroviral treatment and quality of life in Africans living with HIV: 12-month follow-up in Burkina Faso

    PubMed Central

    Jaquet, Antoine; Garanet, Franck; Balestre, Eric; Ekouevi, Didier K.; Azani, Jean Claude; Bognounou, René; Dah, Elias; Kondombo, Jean Charlemagne; Dabis, François; Drabo, Joseph

    2013-01-01

    Introduction The scale-up of highly active antiretroviral therapy (HAART) has led to a significant improvement in survival of the HIV-positive patient but its effects on health-related quality of life (HRQOL) are less known and context-dependent. Our aim was to assess the temporal changes and factors associated with HRQOL among HIV-positive adults initiating HAART in Burkina Faso. Methods HIV-positive people initiating HAART were prospectively included and followed over a one-year period in three HIV clinics of Ouagadougou. HRQOL was assessed at baseline and at each follow-up visit using physical (PHS) and mental (MHS) summary scores derived from the Medical Outcome Study 36-Item short-form health survey (MOS SF-36) questionnaire. Toxicity related to HAART modification and self-reported symptoms were recorded during follow-up visits. Determinants associated with baseline and changes in both scores over a one-year period were assessed using a mixed linear model. Results A total of 344 patients were included. Their median age at baseline was 37 years [interquartile range (IQR) 30–44] and their median CD4 count was 181 cells/mm3 (IQR 97–269). The mean [standard deviation (SD)] PHS score increased from 45.4 (11.1) at baseline to 60.0 (3.1) at 12 months (p<10−4) and the mean (SD) MHS score from 42.2 (8.7) to 43.9 (3.4) (p<10−2). After one year of treatment, patients that experienced on average two symptoms during follow-up presented with significantly lower PHS (63.9) and MHS (43.8) scores compared to patients that presented no symptoms with PHS and MHS of 68.2 (p<10−4) and 45.3 (p<10−3), respectively. Discussion The use of HAART was associated with a significant increase in both physical and mental aspects of the HRQOL over a 12-month period in this urban African population. Perceived symptoms experienced during follow-up visits were associated with a significant impairment in HRQOL. The appropriate and timely management of reported symptoms during the

  15. Antiretroviral drugs do not interfere with bryostatin-mediated HIV-1 latency reversal.

    PubMed

    Martínez-Bonet, Marta; Clemente, Maria Isabel; Álvarez, Susana; Díaz, Laura; García-Alonso, Dolores; Muñoz, Eduardo; Moreno, Santiago; Muñoz-Fernández, Maria Ángeles

    2015-11-01

    Although an effective combination of antiretroviral therapy (cART) controls HIV-1 viraemia in infected patients, viral latency established soon after infection hinders HIV-1 eradication. It has been shown that bryostatin-1 (BRY) inhibits HIV-infection in vitro and reactivates the latent virus through the protein kinase C-NF-κB pathway. We determined the in vitro potential effect of BRY in combination with currently used antiretroviral drugs. BRY alone or in combination with maraviroc (MVC)/Atripla (ATP) was tested for its capacity to reactivate latent virus and inhibit new infections. JLTRG-R5 cells and two latent HIV-1-infected cell lines, J89GFP and THP89GFP, were used as latency models. To quantify HIV infection, the reporter cell line TZM-bl was used. We found that BRY reactivates HIV-1 even in combination with MVC or ATP. Antiretroviral combinations with BRY do not interfere with BRY activity (i.e., the reactivation of latently infected cells) or with the antiviral activity of antiretroviral drugs. In addition, BRY-mediated down-modulation of surface CD4 and CXCR4 was not affected when it was used in combination with other antiretrovirals, and no hyperactivation or high-proliferation effects were observed in primary T cells. Moreover, the BRY treatment was able to reactivate HIV-1 in CD4+ T cells from HIV-1-infected patients under cART. Thus, we propose the use of BRY to purge the viral reservoir and recommend its combination with current antiretroviral treatments.

  16. Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART) Clients in Bale Zone Hospitals, South Eastern Ethiopia

    PubMed Central

    Takele, Abulie; Gashaw, Ketema; Demelash, Habtamu; Nigatu, Dabere

    2016-01-01

    Background Treatment failure defined as progression of disease after initiation of ART or when the anti-HIV medications can’t control the infection. One of the major concerns over the rapid scaling up of ART is the emergence and transmission of HIV drug resistant strains at the population level due to treatment failure. This could lead to the failure of basic ART programs. Thus this study aimed to investigate the predictors of treatment failure among adult ART clients in Bale Zone Hospitals, South east Ethiopia. Methods Retrospective cohort study was employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A total of 4,809 adult ART clients were included in the analysis from these four hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM) curve was used to describe the survival time of ART patients without treatment failure. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of treatment failure. Result The incidence rate of treatment failure was found 9.38 (95% CI 7.79–11.30) per 1000 person years. Male ART clients were more likely to experience treatment failure as compared to females [AHR = 4.49; 95% CI: (2.61–7.73)].Similarly, lower CD4 count (<100 m3/dl) at initiation of ART was found significantly associated with higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46–5.84).Bedridden [AHR = 5.02; 95% CI: (1.98–12.73)] and ambulatory [AHR = 2.12; 95% CI: (1.08–4.07)] patients were more likely to experience treatment failure as compared to patients with working functional status. TB co-infected clients had also higher odds to experience treatment failure [AHR = 3.06; 95% CI: (1.72–5.44)]. Those patients who had developed TB after ART initiation had higher odds to experience treatment failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99–9.54]. Having other opportunistic infection during ART initiation was also

  17. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

    PubMed Central

    Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-01-01

    Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

  18. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial

    PubMed Central

    Ma, Zhong-Min; Utay, Netanya S.; Wook-Chun, Tae; Mann, Surinder; Kashuba, Angela D.; Siewe, Basile; Albanese, Anthony; Troia-Cancio, Paolo; Sinclair, Elizabeth; Somasunderam, Anoma; Yotter, Tammy; Deeks, Steven G.; Landay, Alan; Pollard, Richard B.; Miller, Christopher J.; Moreno, Santiago; Asmuth, David M.

    2016-01-01

    Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory

  19. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.

    PubMed

    Serrano-Villar, Sergio; Sainz, Talia; Ma, Zhong-Min; Utay, Netanya S; Chun, Tae-Wook; Wook-Chun, Tae; Mann, Surinder; Kashuba, Angela D; Siewe, Basile; Albanese, Anthony; Troia-Cancio, Paolo; Sinclair, Elizabeth; Somasunderam, Anoma; Yotter, Tammy; Deeks, Steven G; Landay, Alan; Pollard, Richard B; Miller, Christopher J; Moreno, Santiago; Asmuth, David M

    2016-01-01

    Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory

  20. 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

  1. Using mobile phones to improve clinic attendance amongst an antiretroviral treatment cohort in rural Uganda: a cross-sectional and prospective study.

    PubMed

    Kunutsor, Setor; Walley, John; Katabira, Elly; Muchuro, Simon; Balidawa, Hudson; Namagala, Elizabeth; Ikoona, Eric

    2010-12-01

    We aimed to assess the patterns and dynamics of mobile phone usage amongst an antiretroviral treatment (ART) cohort in rural Uganda and ascertain its feasibility for improving clinic attendance. A cross-sectional study of clients on ART exploring their access to mobile phones and patterns of use was employed. Clinic attendances for antiretroviral drug refills were then monitored prospectively over 28 weeks in 176 patients identified in the cross-sectional survey who had access to mobile phones and had given consent to be contacted. Patients were contacted via voice calls or text messages to remind them about their missed clinic appointments. Of the 276 patients surveyed, 177 (64%) had access to mobile phones with all but one were willing to be contacted for missed visits reminders. Of the 560 total scheduled clinic appointments, 62 (11%) were missed visits. In 79% of episodes in which visits were missed, patients presented for treatment within a mean duration of 2.2 days (SD = 1.2 days) after mobile phone recall. Access to mobile phones was high in this setting. Privacy and confidentiality issues were not considered deterrents. Mobile phones have a potential for use in resource-constrained settings to substantially improve the clinical management of HIV/AIDS.

  2. Perceptions regarding barriers and facilitators to combination antiretroviral therapy adherence among people living with HIV/AIDS in Gujarat, India: A qualitative study

    PubMed Central

    Patel, Sangita; Baxi, Rajendra K.; Patel, Shilpa N.; Golin, Carol E; Mehta, Mansi; Bakshi, Harsh; Shingrapure, Kalpita; Modi, Ekta; Coonor, Priyanka; Mehta, Kedar

    2012-01-01

    Objectives: To know the perceptions regarding barriers and facilitators to cART adherence among people living with HIV/AIDS Materials and Methods: To adapt U.S. based SAFETALK “prevention with positives” intervention to be culturally relevant in Gujarat, India in assisting PLWHA, a formative study was conducted. We conducted 30 in-depth interviews with PLWHA in the local language, assessing the experiences, perceived barriers, and facilitators to combination antiretroviral therapy (cART) among PLWHA in Gujarat. PLWHA were selected from the Voluntary Counseling and Testing Centre (VCTC) in Gujarat. To triangulate interview findings, we conducted two focus group discussions (FGDs) with medical and non-medical providers, respectively. Results: Travel and commuting to clinic, fear of possible physical reactions, high cost of ART from private practitioners, CD4 count being in normal limits and resistance to medication acted as barriers to cART adherence. Initiation of cART was facilitated by family members′ suggestion, advice of treating doctors and counselors, appropriate counseling before starting cART, belief that cART would aid in living a better and longer life and due to lowering of the CD4 count. Interpretation and Conclusions: Our study suggests that several issues need to be considered when providing cART. Further research is needed to study interactions between patients and their health care providers. PMID:23188935

  3. An evaluation of the early effects of a combination antiretroviral therapy programme on the management of AIDS-associated Kaposi's sarcoma in KwaZulu-Natal, South Africa.

    PubMed

    Mosam, A; Uldrick, T S; Shaik, F; Carrara, H; Aboobaker, J; Coovadia, H

    2011-11-01

    Roll-out of combination antiretroviral therapy (cART) in South Africa should impact on AIDS-associated Kaposi's sarcoma (KS). Government provision began in 2003, with 23% coverage for World Health Organization (WHO) stage IV AIDS in 2006. To assess the effect of cART availability on KS management, we evaluated records from 701 KS patients seen at a tertiary oncology centre in KwaZulu-Natal, South Africa, from 1995 to 2006. Associations between cART use and measures of KS care were evaluated. cART availability was 0% prior to 2001, 9.6% (2001-2003) and 44% (2004-2006). Documentation of HIV status increased incrementally from 65% to 92%. cART was associated with chemotherapy administration: 56% on cART versus 17% not on cART (P < 0.001); and less loss to follow-up, 13% on cART versus 38% not on cART (P < 0.001). cART availability improves the care of AIDS-associated KS. Further increases in cART availability for this population are needed in South Africa. PMID:22096054

  4. The Effect of Antiretroviral Treatment on Health Care Utilization in Rural South Africa: A Population-Based Cohort Study

    PubMed Central

    Tanser, Frank C.; Naidu, Kevindra K.; Pillay, Deenan; Bärnighausen, Till

    2016-01-01

    Background The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. Methods and Findings We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009–2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009–2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009–2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per

  5. The Scale of Self-Efficacy Expectations of Adherence to Antiretroviral Treatment: A Tool for Identifying Risk for Non-Adherence to Treatment for HIV

    PubMed Central

    Drachler, Maria de Lourdes; Drachler, Carlos Wietzke; Teixeira, Luciana Barcellos; de Carvalho Leite, José Carlos

    2016-01-01

    Background Identification of risk for non-adherence to treatment is a challenge for personalized care for people living with HIV. Standardized questionnaires of patients’ expectations of their capability to overcome obstacles for treatment adherence may be used as a pre-screening for risk identification. A scale of self-efficacy expectations of adherence to antiretroviral treatment (SEA-ART scale) was previously developed. This study assesses the scale validity in predicting non-adherence to ART in adults living with HIV. Methods and Findings A prospective cohort study applied a 21-item SEA-ART scale to 275 adults in ART treatment at an outpatient public service for HIV in Southern Brazil. ART medications taken were assessed at one-month follow-up; ART adherence was devised as an intake of 95% and more of the prescribed medication. A SEA-ART score was calculated by adding up the scores of all items. Multivariable logistic regression and the Area Under the Receiver-Operating-Characteristic Curve (AUROC) were applied to examine the ability of the SEA-ART score to predict non-adherence at follow-up. The SEA-ART score varied from 21 to 105; mean 93.9; median 103.0. Non-adherence was 30.3% (n = 81/267). The odds of non-adherence was 8% lower for each unit increase of the SEA-ART score; after adjustment for age, sex, formal education and time in treatment (OR = 0.92; 95%CI 0.90–0.95; LRT for linear trend, p = 0.002). The AUROC was 0.80 (95%CI 0.73–0.87; p<0.001). The SEA-ART optimal cut-off value was 101, providing a sensitivity of 76.5%, a specificity of 73.1%, a positive predictive value of 55.4% and a negative predictive value of 87.7%. There was no evidence of difference in sensitivity, and specificity among groups organized by age, gender, formal education and time in treatment. Conclusions The SEA-ART scale appears to have a good capacity to discriminate between adherents and non-adherents at one-month follow-up. Further studies should confirm these results

  6. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    PubMed

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  7. Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

    PubMed Central

    Campbell, Thomas B.; Smeaton, Laura M.; Kumarasamy, N.; Flanigan, Timothy; Klingman, Karin L.; Firnhaber, Cynthia; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; Lalloo, Umesh; Riviere, Cynthia; Sanchez, Jorge; Melo, Marineide; Supparatpinyo, Khuanchai; Tripathy, Srikanth; Martinez, Ana I.; Nair, Apsara; Walawander, Ann; Moran, Laura; Chen, Yun; Snowden, Wendy; Rooney, James F.; Uy, Jonathan; Schooley, Robert T.; De Gruttola, Victor; Hakim, James Gita; Swann, Edith; Barnett, Ronald L.; Brizz, Barbara; Delph, Yvette; Gettinger, Nikki; Mitsuyasu, Ronald T.; Eshleman, Susan; Safren, Steven; Fiscus, Susan A.; Andrade, Adriana; Haas, David W.; Amod, Farida; Berthaud, Vladimir; Bollinger, Robert C.; Bryson, Yvonne; Celentano, David; Chilongozi, David; Cohen, Myron; Collier, Ann C.; Currier, Judith Silverstein; Cu-Uvin, Susan; Eron, Joseph; Flexner, Charles; Gallant, Joel E.; Gulick, Roy M.; Hammer, Scott M.; Hoffman, Irving; Kazembe, Peter; Kumwenda, Newton; Lama, Javier R.; Lawrence, Jody; Maponga, Chiedza; Martinson, Francis; Mayer, Kenneth; Nielsen, Karin; Pendame, Richard B.; Ramratnam, Bharat; Sanne, Ian; Severe, Patrice; Sirisanthana, Thira; Solomon, Suniti; Tabet, Steve; Taha, Taha; van der Horst, Charles; Wanke, Christine; Gormley, Joan; Marcus, Cheryl J.; Putnam, Beverly; Loeliger, Edde; Pappa, Keith A.; Webb, Nancy; Shugarts, David L.; Winters, Mark A.; Descallar, Renard S.; Steele, Joseph; Wulfsohn, Michael; Said, Farideh; Chen, Yue; Martin, John C; Bischofberger, Norbert; Cheng, Andrew; Jaffe, Howard; Sharma, Jabin; Poongulali, S.; Cardoso, Sandra Wagner; Faria, Deise Lucia; Berendes, Sima; Burke, Kelly; Mngqibisa, Rosie; Kanyama, Cecelia; Kayoyo, Virginia; Samaneka, Wadzanai P.; Chisada, Anthony; Faesen, Sharla; Chariyalertsak, Suwat; Santos, Breno; Lira, Rita Alves; Joglekar, Anjali A.; Rosa, Alberto La; Infante, Rosa; Jain, Mamta; Petersen, Tianna; Godbole, Sheela; Dhayarkar, Sampada; Feinberg, Judith; Baer, Jenifer; Pollard, Richard B.; Asmuth, David; Gangakhedkar, Raman R; Gaikwad, Asmita; Ray, M. Graham; Basler, Cathi; Para, Michael F.; Watson, Kathy J.; Taiwo, Babafemi; McGregor, Donna; Balfour, Henry H.; Mullan, Beth; Kim, Ge-Youl; Klebert, Michael K.; Cox, Gary Matthew; Silberman, Martha; Mildvan, Donna; Revuelta, Manuel; Tashima, Karen T.; Patterson, Helen; Geiseler, P. Jan; Santos, Bartolo; Daar, Eric S; Lopez, Ruben; Frarey, Laurie; Currin, David; Haas, David H.; Bailey, Vicki L.; Tebas, Pablo; Zifchak, Larisa; Noel-Connor, Jolene; Torres, Madeline; Sha, Beverly E.; Fritsche, Janice M.; Cespedes, Michelle; Forcht, Janet; O'Brien, William A.; Mogridge, Cheryl; Hurley, Christine; Corales, Roberto; Palmer, Maria; Adams, Mary; Luque, Amneris; Lopez-Detres, Luis; Stroberg, Todd

    2012-01-01

    Background Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected

  8. Sticking to it: the effect of maximally assisted therapy on antiretroviral treatment adherence among individuals living with HIV who are unstably housed.

    PubMed

    Parashar, Surita; Palmer, Alexis K; O'Brien, Nadia; Chan, Keith; Shen, Anya; Coulter, Suzy; Montaner, Julio S G; Hogg, Robert S

    2011-11-01

    Housing is a known determinant of health behaviors, which includes adherence to Antiretroviral Therapy (ART). Within the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) study, unstable housing is inversely associated with adherence. Several comprehensive adherence support services have emerged to improve adherence for unstably housed or otherwise vulnerable populations. The Maximally Assisted Therapy (MAT) program in Vancouver, British Columbia uses a multidisciplinary approach to support HIV-positive clients with a history of addictions or mental illness, many of whom also experience episodic homelessness. This study investigated the association between antiretroviral adherence and use of support services, including the MAT program, amongst people living with HIV and AIDS who are unstably housed in the LISA sample. Of the 212 unstably housed participants, those who attended the MAT program were 4.76 times more likely to be ≥95% adherent (95% CI 1.72-13.13; P = 0.003) than those who did not. The findings suggest that in the absence of sustainable housing solutions, programs such as MAT play an important role in supporting treatment adherence in this population.

  9. Gender differences in HIV disease progression and treatment outcomes among HIV patients one year after starting antiretroviral treatment (ART) in Dar es Salaam, Tanzania

    PubMed Central

    2013-01-01

    Background We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. Methods We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. Results Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). Conclusion We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological

  10. Retention of HIV-infected children on antiretroviral treatment in HIV care and treatment programs in Kenya, Mozambique, Rwanda and Tanzania

    PubMed Central

    McNairy, Margaret L.; Lamb, Matthew R.; Carter, Rosalind J.; Fayorsey, Ruby; Tene, Gilbert; Mutabazi, Vincent; Gusmao, Eduarda; Panya, Millembe; Sheriff, Mushin; Abrams, Elaine J.

    2016-01-01

    Background Retention of children in HIV care is essential for prevention of disease progression and mortality. Methods Retrospective cohort of children (0 to <15 years) initiating antiretroviral treatment (ART) at health facilities in Kenya, Mozambique, Rwanda and Tanzania, January 2005–June 2011. Retention was defined as the proportion of children known to be alive and attending care at their initiation facility; lost to follow-up (LTF) was defined as no clinic visit for > 6 months. Cumulative incidence of ascertained survival and retention after ART initiation was estimated through 24 months using Kaplan-Meier methods. Factors associated with LTF and death were assessed using Cox proportional hazard modeling. Results 17,712 children initiated ART at 192 facilities: median age was 4.6 years (IQR: 1.9–8.3), median CD4 was 15% (IQR: 10–20) for children < 5 years and 265 cells/uL (IQR: 111–461) for children ≥ 5 years. At 12 and 24 months, 80% and 72% of children were retained with 16% and 22% LTF and 5% and 7% known deaths respectively. Retention ranged from 71–95% and 62–93% at 12 and 24 months across countries, and was lowest for children < 1 year (51% at 24 months). LTF and death were highest in children < 1 year of age and children with advanced disease. Conclusion Retention was lowest in young children and differed across country programs. Young children and those with advanced disease are at highest risk for LTF and death. Further evaluation of patient- and program-level factors is needed to improve health outcomes. PMID:23111575

  11. Individualization of antiretroviral therapy

    PubMed Central

    Pavlos, Rebecca; Phillips, Elizabeth J

    2012-01-01

    Antiretroviral therapy (ART) has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual’s environment that may be dynamic over time]) information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care. PMID:23226059

  12. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks

    PubMed Central

    Scarsi, Kimberly K.; Darin, Kristin M.; Nakalema, Shadia; Back, David J.; Byakika-Kibwika, Pauline; Else, Laura J.; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E.; Merry, Concepta; Lamorde, Mohammed

    2016-01-01

    Background. Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. Methods. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus–infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Results. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Conclusions. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. Clinical Trials Registration. NCT01789879. PMID:26646680

  13. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care. PMID:27092564

  14. 'Dented' and 'resuscitated' masculinities: the impact of HIV diagnosis and/or enrolment on antiretroviral treatment on masculine identities in rural eastern Uganda.

    PubMed

    Siu, Godfrey E; Wight, Daniel; Seeley, Janet

    2014-01-01

    There is limited research on the impact of HIV or its treatment on men's identity construction and gender roles in sub-Saharan Africa. Based on in-depth research with 26 men in rural Uganda, this article discusses men's vulnerabilities and shifting gender relations and sense of masculinity resulting from HIV infection or enrolment on treatment in eastern Uganda. The findings suggest two broad categories of masculinity: respectable and reputational. HIV infection and illness dented masculinity as men lost authority within the domestic sphere. A weakened provider role and over-reliance on wives and children undermined masculinity as family head, and social sanctioning of their sexual activity, undermined conventional masculine identities predicted on reputation. However, treatment led to a more reflexive approach to demonstrating masculinity, increased attentiveness to health and restored hope to father children free of HIV, resuscitating respectable masculinities. The balance between eroded and restored masculinity varied between men by their treatment history, age, family composition and state of health. HIV support agencies need to pay attention to the way HIV and antiretroviral treatment (ART) influence men's perception of their masculinity and support them to overcome the anxieties about dented or eroded masculinity, while building on the positive ways in which treatment restores masculinity to support men's adherence to HIV treatment. In particular, there is a need to support men's engagement in productive activities that bring income so that men can regain their provider roles following ART and restore their respectability in both the public and the domestic sphere.

  15. ‘Dented’ and ‘Resuscitated’ masculinities: The impact of HIV diagnosis and/or enrolment on antiretroviral treatment on masculine identities in rural eastern Uganda

    PubMed Central

    Siu, Godfrey E.; Wight, Daniel; Seeley, Janet

    2014-01-01

    Abstract There is limited research on the impact of HIV or its treatment on men's identity construction and gender roles in sub-Saharan Africa. Based on in-depth research with 26 men in rural Uganda, this article discusses men's vulnerabilities and shifting gender relations and sense of masculinity resulting from HIV infection or enrolment on treatment in eastern Uganda. The findings suggest two broad categories of masculinity: respectable and reputational. HIV infection and illness dented masculinity as men lost authority within the domestic sphere. A weakened provider role and over-reliance on wives and children undermined masculinity as family head, and social sanctioning of their sexual activity, undermined conventional masculine identities predicted on reputation. However, treatment led to a more reflexive approach to demonstrating masculinity, increased attentiveness to health and restored hope to father children free of HIV, resuscitating respectable masculinities. The balance between eroded and restored masculinity varied between men by their treatment history, age, family composition and state of health. HIV support agencies need to pay attention to the way HIV and antiretroviral treatment (ART) influence men's perception of their masculinity and support them to overcome the anxieties about dented or eroded masculinity, while building on the positive ways in which treatment restores masculinity to support men's adherence to HIV treatment. In particular, there is a need to support men's engagement in productive activities that bring income so that men can regain their provider roles following ART and restore their respectability in both the public and the domestic sphere. PMID:25444303

  16. Role of Intestinal Myofibroblasts in HIV-Associated Intestinal Collagen Deposition and Immune Reconstitution following Combination Antiretroviral Therapy

    PubMed Central

    Asmuth, David M; Pinchuk, Irina V; Wu, Jian; Vargas, Gracie; Chen, Xiaoli; Mann, Surinder; Albanese, Anthony; Ma, Zhong-Min; Saroufeem, Ramez; Melcher, Gregory P; Troia-Cancio, Paolo; Torok, Natalie J; Miller, Christopher J; Powell, Don W.

    2015-01-01

    Objective To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associated fibrosis in GALT. Design Profibrotic changes within the secondary lymphoid organs and mucosa has been implicated in failed immune reconstitution following effective cART. Microbial translocation is believed to be sustaining these systemic inflammatory pathways. IMFs are non-professional antigen-presenting cells with both immunoregulatory and mesenchymal functions that are ideally positioned to respond to translocating microbial antigen. Methods Duodenal biopsies obtained from patients naïve to cART underwent trichrome staining and examined for TGF-β expression. Combined immunostaining and second harmonic generation-analysis was used to determine IMF activation and collagen deposition. Confocal microscopy was performed to examine for IMF activation and TLR4 expression. Finally, primary IMF cultures were stimulated with LPS to demonstrate expression of inflammatory biomarkers. Results The expression of the fibrosis-promoting molecule, TGF-β1, is significantly increased in duodenal biopsies from HIV patients naïve to cART and negatively correlated with subsequent peripheral CD4 recovery. The TGFβ1 increases coincided with an increase in collagen deposition in duodenal mucosa in tissue area adjacent to IMFs. We also observed that IMFs expressed TLR4 and had an activated phenotype since they were positive for fibroblast activation protein. Finally, stimulation of IMFs from HIV patients with TLR4 resulted in significantly increased expression of profibrotic molecules, TGF-β1 and IL-6. Conclusions Our data support the hypothesis that activated IMFs may be among the major cells contributing to the profibrotic changes and thus, the establishment and maintenance of systemic inflammation interfering with immune reconstitution in HIV patients. PMID:25784439

  17. When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries

    PubMed Central

    2012-01-01

    Background Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 109 cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. Objective To identify the optimal CD4 cell count at which cART should be initiated. Design Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 109 cells/L. Setting HIV clinics in Europe and the Veterans Health Administration system in the United States. Patients 20 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 109 cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 109 cells/L and were included in the analysis. Measurements Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Results Compared with initiating cART at the CD4 cell count threshold of 0.500 × 109 cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Conclusion Initiation of cART at a threshold CD4 count of 0.500 × 109 cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 ×109 cells/L. Primary Funding Source National Institutes of Health. PMID:21502648

  18. The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

    PubMed

    Spada, Celso; Treitinger, Arício; Reis, Marcellus; Masokawa, Ivete Y; Verdi, Júlio C; Luiz, Magali C; Silveira, Mariete V S; Michelon, Cleonice M; Avila-Junior, Silvio; Gil, lone D O; Ostrowskyl, Stephanie

    2002-05-01

    Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

  19. The Experience of Antiretroviral Treatment for Black West African Women who are HIV Positive and Living in London: An Interpretative Phenomenological Analysis.

    PubMed

    Spiers, Johanna; Smith, Jonathan A; Poliquin, Elizabeth; Anderson, Jane; Horne, Rob

    2016-09-01

    Antiretroviral therapy (ART) offers a powerful intervention in HIV but effectiveness can be compromised by inadequate adherence. This paper is a detailed examination of the experience of medication in a purposively selected group of people living with HIV. In-depth interviews were conducted with 10 HIV positive, West African women of black heritage living in London, UK. This group was of interest since it is the second largest group affected by HIV in the UK. Interviews were subjected to interpretative phenomenological analysis, an idiographic, experiential, qualitative approach. The paper details the women's negative experience of treatment. ART can be considered difficult and unrelenting and may be disconnected from the women's sense of health or illness. Participants' social context often exacerbated the difficulties. Some reported an improvement in their feelings about the medication over time. These findings point to some intrinsic and social motivators which could act as spurs to adherence.

  20. The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis

    PubMed Central

    Odone, Anna; Amadasi, Silvia; White, Richard G.; Cohen, Theodore; Grant, Alison D.; Houben, Rein M. G. J.

    2014-01-01

    Objective To quantify the impact of antiretroviral therapy (ART) on mortality in HIV-positive people during tuberculosis (TB) treatment. Design We conducted a systematic literature review and meta-analysis. Studies published from 1996 through February 15, 2013, were identified by searching electronic resources (Pubmed and Embase) and conference books, manual searches of references, and expert consultation. Pooled estimates for the outcome of interest were acquired using random effects meta-analysis. Subjects The study population included individuals receiving ART before or during TB treatment. Main Outcome Measures Main outcome measures were: (i) TB-case fatality ratio (CFR), defined as the proportion of individuals dying during TB treatment and, if mortality in HIV-positive people not on ART was also reported, (ii) the relative risk of death during TB treatment by ART status. Results Twenty-one studies were included in the systematic review. Random effects pooled meta-analysis estimated the CFR between 8% and 14% (pooled estimate 11%). Among HIV-positive TB cases, those receiving ART had a reduction in mortality during TB treatment of between 44% and 71% (RR = 0.42, 95%CI: 0.29–0.56). Conclusion Starting ART before or during TB therapy reduces the risk of death during TB treatment by around three-fifths in clinical settings. National programmes should continue to expand coverage of ART for HIV positive in order to control the dual epidemic. PMID:25391135

  1. A ‘good hospital’: Nurse and patient perceptions of good clinical care for HIV-positive people on antiretroviral treatment in rural Zimbabwe—A mixed-methods qualitative study

    PubMed Central

    Campbell, Catherine; Scott, Kerry; Madanhire, Claudius; Nyamukapa, Constance; Gregson, Simon

    2011-01-01

    Background Antiretroviral treatment for HIV is gradually being made available across sub-Saharan Africa. With antiretroviral treatment, HIV can be approached as a chronic, manageable condition rather than a shorter-term issue of palliative care. This treatment involves repeated interaction between health staff and patients for ongoing check-ups and prescription refills. Objective This study aimed to understand patient and healthcare staff perceptions of good clinical antiretroviral treatment care. Design Over 100 h of ethnographic observation at healthcare sites; interviews and focus groups with 25 healthcentre workers (mostly nurses), 53 HIV-positive adults taking ARVs and 40 carers of children on ART. The data were analyzed using thematic content analysis. Setting Three healthcare sites providing free antiretroviral drugs in rural Zimbabwe, where the adult HIV infection rate is approximately 20%. Results Contrary to reports of poor antiretroviral treatment adherence and task-oriented rather than patient-oriented nursing, our study found great patient commitment to adherence, outstanding nurse dedication and a pervasive sense of hope about coping with HIV. Within this context however there were some situations where patients and nurses had different expectations of the medical encounter, leading to stress and dissatisfaction. Patients and staff both emphasized the importance of nurse kindness, understanding, confidentiality and acceptance (i.e. treating HIV patients ‘like normal’) and patient adherence to medical directions. However, nurses at times overlooked the negative effects of long wait times and frequent hospital visits. Further, nurses sometimes conflated medical adherence with general patient obedience in all aspects of the nurse–patient relationships. Patients and staff were frustrated by the ambiguity and unpredictability surrounding key elements of hospital visits such as how much patients had to pay for service, how long it would take to be

  2. Combined treatment in carcinoma of the nasopharynx

    SciTech Connect

    Souhami, L.; Rabinowits, M.

    1988-08-01

    From October 1982 to August 1984, 30 previously untreated patients with biopsy-proven carcinoma of the nasopharynx, stage III (26.5%) and stage IV (73.5%), received combined radiotherapy (6,000 to 7,000 cGy over a period of 7 to 7.5 weeks) and chemotherapy (mitomycin-C 10 mg/M2, IV; 5-fluorouracil 750 mg/M2, IV; and methotrexate 30 mg/M2, IV) concomitantly. There were 20 males and 10 females, with a median age of 40 years. Minimal follow-up duration was 24 months. Actuarial overall survival rate at 48 months was 49%. Complete local response was achieved in 75% of the patients, with 31% of the cases failing distantly. The complication rate was high and included severe mucositis, xerostomia, and septicemia (fatal in two cases). Despite high local disease control, survival rate did not increase. A randomized trial is urgently needed to establish whether or not combined treatment is of value in advanced carcinoma of the nasopharynx.

  3. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort

    PubMed Central

    Walker, AS; Ford, D; Gilks, CF; Munderi, P; Ssali, F; Reid, A; Katabira, E; Grosskurth, H; Mugyenyi, P; Hakim, J; Darbyshire, JH; Gibb, DM; Babiker, AG

    2010-01-01

    Summary Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. Methods Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. Findings 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68]. Interpretation Our results reinforce WHO guidelines and provide strong motivation for provision

  4. Early Linkage to HIV Care and Antiretroviral Treatment among Men Who Have Sex with Men — 20 Cities, United States, 2008 and 2011

    PubMed Central

    Hoots, Brooke E.; Finlayson, Teresa J.; Wejnert, Cyprian; Paz-Bailey, Gabriela

    2015-01-01

    Early linkage to care and antiretroviral (ARV) treatment are associated with reduced HIV transmission. Male-to-male sexual contact represents the largest HIV transmission category in the United States; men who have sex with men (MSM) are an important focus of care and treatment efforts. With the release of the National HIV/AIDS Strategy and expanded HIV treatment guidelines, increases in early linkage to care and ARV treatment are expected. We examined differences in prevalence of early linkage to care and ARV treatment among HIV-positive MSM between 2008 and 2011. Data are from the National HIV Behavioral Surveillance System, which monitors behaviors among populations at high risk of HIV infection in 20 U.S. cities with high AIDS burden. MSM were recruited through venue-based, time-space sampling. Prevalence ratios comparing 2011 to 2008 were estimated using linear mixed models. Early linkage was defined as an HIV clinic visit within 3 months of diagnosis. ARV treatment was defined as use at interview. Prevalence of early linkage to care was 79% (187/236) in 2008 and 83% (241/291) in 2011. In multivariable analysis, prevalence of early linkage did not differ significantly between years overall (P = 0.44). Prevalence of ARV treatment was 69% (790/1,142) in 2008 and 79% (1,049/1,336) in 2001. In multivariable analysis, ARV treatment increased overall (P = 0.0003) and among most sub-groups. Black MSM were less likely than white MSM to report ARV treatment (P = 0.01). While early linkage to care did not increase significantly between 2008 and 2011, ARV treatment increased among most sub-groups. Progress is being made in getting MSM on HIV treatment, but more efforts are needed to decrease disparities in ARV coverage. PMID:26176856

  5. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  6. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

    PubMed Central

    Revell, Andrew D.; Wang, Dechao; Pozniak, Anton; Montaner, Julio S.; Lane, H. Clifford; Larder, Brendan A.

    2013-01-01

    Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%). Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings. PMID:24175292

  7. Change in Vitamin D Levels Occurs Early after Antiretroviral Therapy Initiation and Depends on Treatment Regimen in Resource-Limited Settings

    PubMed Central

    Havers, Fiona P.; Detrick, Barbara; Cardoso, Sandra W.; Berendes, Sima; Lama, Javier R.; Sugandhavesa, Patcharaphan; Mwelase, Noluthando H.; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    Study Background Vitamin D has wide-ranging effects on the immune system, and studies suggest that low serum vitamin D levels are associated with worse clinical outcomes in HIV. Recent studies have identified an interaction between antiretrovirals used to treat HIV and reduced serum vitamin D levels, but these studies have been done in North American and European populations. Methods Using a prospective cohort study design nested in a multinational clinical trial, we examined the effect of three combination antiretroviral (cART) regimens on serum vitamin D levels in 270 cART-naïve, HIV-infected adults in nine diverse countries, (Brazil, Haiti, Peru, Thailand, India, Malawi, South Africa, Zimbabwe and the United States). We evaluated the change between baseline serum vitamin D levels and vitamin D levels 24 and 48 weeks after cART initiation. Results Serum vitamin D levels decreased significantly from baseline to 24 weeks among those randomized to efavirenz/lamivudine/zidovudine (mean change: −7.94 [95% Confidence Interval (CI) −10.42, −5.54] ng/ml) and efavirenz/emtricitabine/tenofovir-DF (mean change: −6.66 [95% CI −9.40, −3.92] ng/ml) when compared to those randomized to atazanavir/emtricitabine/didanosine-EC (mean change: −2.29 [95% CI –4.83, 0.25] ng/ml). Vitamin D levels did not change significantly between week 24 and 48. Other factors that significantly affected serum vitamin D change included country (p<0.001), season (p<0.001) and baseline vitamin D level (p<0.001). Conclusion Efavirenz-containing cART regimens adversely affected vitamin D levels in patients from economically, geographically and racially diverse resource-limited settings. This effect was most pronounced early after cART initiation. Research is needed to define the role of Vitamin D supplementation in HIV care. PMID:24752177

  8. Simplification Strategies to Reduce Antiretroviral Drug Exposure: Progress and Prospects

    PubMed Central

    McKinnon, John E.; Mellors, John W.; Swindells, Susan

    2009-01-01

    Current US guidelines for initial therapy of HIV-1 infection recommend daily, life-long treatment with a combination of three antiretroviral drugs consisting of two nucleoside analog reverse transcriptase (RT) inhibitors and a nonnucleoside RT inhibitor or a protease inhibitor. Although this approach has been successful in reducing morbidity and mortality from HIV-1 infection, concerns remain about adverse events from chronic drug exposure, the requirement for daily medication adherence, the risk of HIV-1 drug resistance, and high treatment costs. The availability of antiretrovirals that are co-formulated and dosed once-daily have reduced pill burden and have simplified dosing schedules, but have not lowered drug exposure or cost. These limitations have stimulated research into drug-sparing strategies including intermittent therapy and simplified maintenance regimens. Randomized clinical trials have shown greater mortality with intermittent therapy compared with continuous therapy leading to rejection of this strategy. Pilot studies of simplified maintenance therapy with a ritonavir-boosted protease inhibitor alone have shown more promise, although concerns remain. This article reviews progress in simplification of antiretroviral therapy, recent clinical trial results, and prospects for the future. PMID:19320232

  9. Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India

    PubMed Central

    Mahajan, Raman; Das, Pradeep; Isaakidis, Petros; Sunyoto, Temmy; Sagili, Karuna D; Lima, Marıa Angeles; Mitra, Gaurab; Kumar, Deepak; Pandey, Krishna; Van geertruyden, Jean-Pierre; Boelaert, Marleen; Burza, Sakib

    2015-01-01

    Background. There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen. Methods. This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART). Results. 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4–18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse. Conclusions. In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients. PMID:26129756

  10. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia

    PubMed Central

    Ayalew, Mohammed Biset; Kumilachew, Dawit; Belay, Assefa; Getu, Samson; Teju, Derso; Endale, Desalegn; Tsegaye, Yemisirach; Wale, Zebiba

    2016-01-01

    Background Antiretroviral therapy (ART) restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital. Patients and methods A retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients’ sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. P<0.05 was used to declare association. Results Among the 340 patients enrolled, 205 were females (60.3%). The mean age at ART initiation was 34.4 years. A total of 14 (4.1%) patients were found to have treatment failure. The median duration of treatment failure from initiation of treatment was 17.5 months (8–36 months). Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure. Conclusion The prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm3).

  11. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia

    PubMed Central

    Ayalew, Mohammed Biset; Kumilachew, Dawit; Belay, Assefa; Getu, Samson; Teju, Derso; Endale, Desalegn; Tsegaye, Yemisirach; Wale, Zebiba

    2016-01-01

    Background Antiretroviral therapy (ART) restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital. Patients and methods A retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients’ sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. P<0.05 was used to declare association. Results Among the 340 patients enrolled, 205 were females (60.3%). The mean age at ART initiation was 34.4 years. A total of 14 (4.1%) patients were found to have treatment failure. The median duration of treatment failure from initiation of treatment was 17.5 months (8–36 months). Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure. Conclusion The prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm3). PMID:27621669

  12. Amniocentesis in the HIV-infected pregnant woman: Is there still cause for concern in the era of combination antiretroviral therapy?

    PubMed Central

    Andany, Nisha; Letchumanan, Michelle; Bondy, Lise; Murphy, Kellie; Loutfy, Mona R

    2013-01-01

    The current standard of care in Canadian obstetrical practice is to offer pregnant women the opportunity for prenatal investigation to diagnose congenital abnormalities. Prenatal amniocentesis is Canada’s most commonly practiced invasive procedure for the diagnosis of chromosomal and single gene disorders. The potential risk of intrapartum HIV transmission during amniocentesis raises several ethical concerns and limits the availability of prenatal genetic testing for HIV-positive pregnant women. Complete virological suppression with antiretroviral therapy may alleviate the risk of mother-to-child transmission during amniocentesis and increase accessibility of this important diagnostic tool in the HIV-positive population. The present report describes a case involving a 32-year-old HIV-positive pregnant woman whose plasma viral load was undetectable on antiretroviral therapy; she underwent successful prenatal amniocentesis without transmission of HIV to her infant. PMID:24421839

  13. Amniocentesis in the HIV-infected pregnant woman: Is there still cause for concern in the era of combination antiretroviral therapy?

    PubMed

    Andany, Nisha; Letchumanan, Michelle; Bondy, Lise; Murphy, Kellie; Loutfy, Mona R

    2013-01-01

    The current standard of care in Canadian obstetrical practice is to offer pregnant women the opportunity for prenatal investigation to diagnose congenital abnormalities. Prenatal amniocentesis is Canada's most commonly practiced invasive procedure for the diagnosis of chromosomal and single gene disorders. The potential risk of intrapartum HIV transmission during amniocentesis raises several ethical concerns and limits the availability of prenatal genetic testing for HIV-positive pregnant women. Complete virological suppression with antiretroviral therapy may alleviate the risk of mother-to-child transmission during amniocentesis and increase accessibility of this important diagnostic tool in the HIV-positive population. The present report describes a case involving a 32-year-old HIV-positive pregnant woman whose plasma viral load was undetectable on antiretroviral therapy; she underwent successful prenatal amniocentesis without transmission of HIV to her infant.

  14. The HIV Treatment Gap: Estimates of the Financial Resources Needed versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020

    PubMed Central

    2015-01-01

    Background The World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available. Methods and Findings Current coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries’ current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS “90-90-90” ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead. We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under

  15. The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment.

    PubMed

    Bernal Morell, Enrique; Serrano Cabeza, José; Muñoz, Ángeles; Marín, Irene; Masiá, Mar; Gutiérrez, Félix; Cano, Alfredo

    2016-07-01

    Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 ± 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 ± 0.16 mm vs. 0.63 ± 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019

  16. Antiretroviral Treatment Scale-Up and Tuberculosis Mortality in High TB/HIV Burden Countries: An Econometric Analysis

    PubMed Central

    Yan, Isabel; Bendavid, Eran; Korenromp, Eline L.

    2016-01-01

    Introduction Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries. Methods We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects. Results Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (p<0.001), and 31% fewer deaths in 2011. TB mortality was higher at higher HIV prevalence (p<0.001), but not related to coverage of isoniazid preventive therapy, cotrimoxazole preventive therapy, or other covariates. Conclusion This econometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data. PMID:27536864

  17. Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter analysis

    PubMed Central

    Zaccarelli, Mauro; Fabbiani, Massimiliano; Pinnetti, Carmela; Borghi, Vanni; Giannetti, Alberto; Sterrantino, Gaetana; Lorenzini, Patrizia; Latini, Alessandra; Loiacono, Laura; Colafigli, Manuela; Ammassari, Adriana; D'Ettorre, Gabriella; Plazzi, Maddalena; Di Giambenedetto, Simona; Antinori, Andrea

    2014-01-01

    Background To assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure. Materials and Methods Patients starting DT regimen composed by a boosted protease inhibitor (PI/r): darunavir (DRV/r), lopinavir (LPVr) or atazanavir (ATV/r) plus a second drug: raltegravir (RAL), maraviroc (MRV) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF), this one generally used in HBV co-infected patients, were included. The effect of each drug as well as other clinical and virological cofactors over treatment failure was assessed using survival analysis. Results Overall, 480 patients from six reference Italian centres were included: all switched to DT with HIV-RNA <500 cp/µL, 376 of them at <50 cp/µL. Patients who switched at <50 cp/µL showed a significant lower risk of treatment failure (13.3% versus 23.3% at 1 year and 28.0% versus 44.6% at 3 years, p=0.005), thus the analysis was focused on this subgroup. Among the patients who switched at <50 cp/µL, the proportion of drug used in DT was: DRV/r 63.0%, RAL 53.7%, ETR 19.4%, ATV/r 18.4%, MRV 17.3%, LPV/r 12.8%, TDF 6.4% and 3TC 5.9%; DRV/r-RAL was the most widely used combination: 32.5%. Treatment failure was observed in 78 patients, of whom 38 virological and 35 for toxicity/intolerance, one patient died during follow-up and four patients interrupted for personal decision with undetectable HIV-RNA. At Cox Model, adjusted by gender, age, non-Italian origin, AIDS diagnosis, time on cART, number of regimens, CD4 nadir, baseline CD4, all the drugs had a positive effect on probability of failure (Figure), however the effect was significant for DRV/r (HR:0.21, 95% CI 0.07–0.59, p=0.03), ATV/r (0.30, 0.09–0.97, p=0.044) and RAL (0.37, 0.15–0.93, p=0.034); higher CD4 count at baseline was also associated with lower risk of failure while number of previous regimens with a higher risk. Moreover, ATV/r was found significant associated with significant higher risk of failure by

  18. Longitudinal relationships between antiretroviral treatment adherence and discrimination due to HIV-serostatus, race, and sexual orientation among African-American men with HIV.

    PubMed

    Bogart, Laura M; Wagner, Glenn J; Galvan, Frank H; Klein, David J

    2010-10-01

    African-Americans show worse HIV disease outcomes compared to Whites. Health disparities may be aggravated by discrimination, which is associated with worse health and maladaptive health behaviors. We examined longitudinal effects of discrimination on antiretroviral treatment adherence among 152 HIV-positive Black men who have sex with men. We measured adherence and discrimination due to HIV-serostatus, race/ethnicity, and sexual orientation at baseline and monthly for 6 months. Hierarchical repeated-measures models tested longitudinal effects of each discrimination type on adherence. Over 6 months, participants took 60% of prescribed medications on average; substantial percentages experienced discrimination (HIV-serostatus, 38%; race/ethnicity, 40%; and sexual orientation, 33%). Greater discrimination due to all three characteristics was significantly bivariately associated with lower adherence (all p's < 0.05). In the multivariate model, only racial discrimination was significant (p < 0.05). Efforts to improve HIV treatment adherence should consider the context of multiple stigmas, especially racism.

  19. Gender-related differences in outcomes and attrition on antiretroviral treatment among an HIV-infected patient cohort in Zimbabwe: 2007–2010

    PubMed Central

    Takarinda, Kudakwashe C.; Harries, Anthony D.; Shiraishi, Ray W.; Mutasa-Apollo, Tsitsi; Abdul-Quader, Abu; Mugurungi, Owen

    2016-01-01

    SUMMARY Objectives To determine (1) gender-related differences in antiretroviral therapy (ART) outcomes, and (2) gender-specific characteristics associated with attrition. Methods This was a retrospective patient record review of 3919 HIV-infected patients aged ≥15 years who initiated ART between 2007 and 2009 in 40 randomly selected ART facilities countrywide. Results Compared to females, males had more documented active tuberculosis (12% vs. 9%; p < 0.02) and a lower median CD4 cell count (117 cells/μl vs. 143 cells/μl; p < 0.001) at ART initiation. Males had a higher risk of attrition (adjusted hazard ratio (AHR) 1.28, 95% confidence interval (CI) 1.10–1.49) and mortality (AHR 1.56, 95% CI 1.10–2.20). Factors associated with attrition for both sexes were lower baseline weight (<45 kg and 45–60 kg vs. >60 kg), initiating ART at an urban health facility, and care at central/provincial or district/mission hospitals vs. primary healthcare facilities. Conclusions Our findings show that males presented late for ART initiation compared to females. Similar to other studies, males had higher patient attrition and mortality compared to females and this may be attributed in part to late presentation for HIV treatment and care. These observations highlight the need to encourage early HIV testing and enrolment into HIV treatment and care, and eventually patient retention on ART, particularly amongst men. PMID:25462184

  20. COMBINED-SEWER OVERFLOW CONTROL AND TREATMENT

    EPA Science Inventory

    Combined-sewer overflow (CSO), along with sanitary-sewer overflow and stormwater are significant contributors of contamination to surface waters. During a rain event, the flow in a combined sewer system may exceed the capacity of the intercepting sewer leading to the wastewater t...

  1. Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia.

    PubMed

    Ebissa, Getachew; Deyessa, Negusse; Biadgilign, Sibhatu

    2015-01-01

    Highly active antiretroviral therapy (HAART) is the breakthrough in care and treatment of people living with HIV, leading to a reduction in mortality and an improvement in the quality of life. Without antiretroviral treatment, most HIV-infected children die before their fifth birthday. So the objective of this study is to determine the mortality and associated factors in a cohort of HIV-infected children receiving ART in Ethiopia. A multicentre facility-based retrospective cohort study was done in selected pediatric ART units in hospitals found in Addis Ababa, Ethiopia. The probability of survival was estimated using the Kaplan-Meier method, and multivariate analysis by Cox proportional hazards regression models was conducted to determine the independent predictor of survival. A total of 556 children were included in this study. Of the total children, 10.4% were died in the overall cohort. More deaths (70%) occurred in the first 6 months of ART initiation, and the remaining others were still on follow-up at different hospitals. Underweight (moderate and severe; HR: 10.10; 95% CI: 2.08, 28.00; P = 0.004; and HR: 46.69; 95% CI: 9.26, 200.45; P < 0.01, respectively), advanced disease stage (WHO clinical stages III and IV; HR: 10.13: 95% CI: 2.25, 45.58; P = 0.003), poor ART adherence (HR: 11.72; 95% CI: 1.60, 48.44; P = 0.015), and hemoglobin level less than 7 g/dl (HR: 4.08: 95% CI: 1.33, 12.56; P = 0.014) were confirmed as significant independent predictors of death after controlling for other factors. Underweight, advanced disease stage, poor adherence to ART, and anemia appear to be independent predictor of survival in HIV-infected children receiving HAART at the pediatric units of public hospitals in Ethiopia. Nutritional supplementations, early initiation of HAART, close supervision, and monitoring of patients during the first 6 months, the follow up period is recommended.

  2. Self-reported side-effects of anti-retroviral treatment among IDUs: a 7-year longitudinal study (APROCO-COPILOTE COHORT ANRS CO-8).

    PubMed

    Carrieri, Maria Patrizia; Villes, Virginie; Raffi, François; Protopopescu, Camelia; Preau, Marie; Salmon, Dominique; Taieb, Audrey; Lang, Jean-Marie; Verdon, Renaud; Chene, Geneviève; Spire, Bruno

    2007-08-01

    The introduction of potent anti-retroviral treatment (ART) has transformed HIV disease into a chronic condition with the prospect, for the patient, of strict adherence to effective but life-long treatments. Within this framework, a major issue that can negatively affect adherence is the side-effects of the treatment. To date, studies documenting how individuals HIV-infected through drug injection (IDUs) experience ART-related side effects are sparse. Longitudinal data collected from the APROCO-COPILOTE cohort have been used to compare the experience of ART-related side-effects who have been HIV-infected via injecting drug use and non-IDU patients. A 20-item list was used to collect self-reported side-effects over a 7-year follow up period. Of 922 patients, 15% were IDUs. At any given visit, IDUs reported a significantly higher number of side-effects and had approximately twice the risk of reporting any side effect than non-IDUs. Most commonly reported side-effects were dry skin, fatigue, vomiting, bone troubles, insomnia. After adjustment for social conditions, depressive symptoms, use of sleeping pills and time since HIV diagnosis, IDUs reported experiencing significantly more side-effects than non-IDUs. Whether or not this is related to sensitivity to pain or to other comorbidities is difficult to establish. Further research is needed to understand how substitution treatment can mediate the relationship between exposure to opioids and side-effects. Providing appropriate care to reduce side-effects, thereby increasing adherence to ART in this population, remains a major challenge especially in those countries scaling up ART. Incorporating symptom management and improving access to analgesic medications within a model of comprehensive care for HIV-infected IDUs, could reduce the impact of drug-related and HIV-related harms and induce better long-term treatment outcomes and quality of life. PMID:17689377

  3. Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda.

    PubMed

    van Griensven, Johan; Zachariah, Rony; Rasschaert, Freya; Mugabo, Jules; Atté, Edi F; Reid, Tony

    2010-02-01

    This cohort study was conducted to report on the incidence, timing and risk factors for stavudine (d4T)- and nevirapine (NVP)-related severe drug toxicity (requiring substitution) with a generic fixed-dose combination under program conditions in Kigali, Rwanda. Probability of 'time to first toxicity-related drug substitution' was estimated using the Kaplan-Meier method and Cox-proportional hazards modeling was used to identify risk factors. Out of 2190 adults (median follow-up: 1.5 years), d4T was replaced in 175 patients (8.0%) for neuropathy, 69 (3.1%) for lactic acidosis and 157 (7.2%) for lipoatrophy, which was the most frequent toxicity by 3 years of antiretroviral treatment (ART). NVP was substituted in 4.9 and 1.3% of patients for skin rash and hepatotoxicity, respectively. Use of d4T 40 mg was associated with increased risk of lipoatrophy and early (<6 months) neuropathy. Significant risk factors associated with lactic acidosis and late neuropathy included higher baseline body weight. Older age and advanced HIV disease increased the risk of neuropathy. Elevated baseline liver tests and older age were identified as risk factors for NVP-related hepatotoxicity. d4T is associated with significant long-term toxicity. d4T-dose reduction, increased access to safer ART in low-income countries and close monitoring for those at risk are all relevant strategies.

  4. Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study

    PubMed Central

    2011-01-01

    Objective To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF) 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU). Methods European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naïve, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. Results Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing = failure) at week 48, 34% of patients (23/67; 95% CI: 23%-47%) had plasma HIV-1 RNA < 50 copies/mL. Using an intent-totreat missing = excluded approach, the week 48 proportion of patients with plasma HIV-1 RNA < 50 copies/mL increased to 56% (23/41; 95% CI: 40%-72%). Mean (standard deviation) increase from baseline in CD4+ cell count at week 48 was 176 (242) cells/mm3. Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. Conclusions Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients. PMID:22024421

  5. Osteoporosis and multiple fractures in an antiretroviral-naive, HIV-positive child.

    PubMed

    Soler Palacin, P; Torrent, A; Rossich, R; Moraga, F A; Yeste, D; Carreño, J C; Encabo, G; Figueras, C

    2007-08-01

    As a result of the increased incidence of osteopenia and osteoporosis in HIV-infected patients, numerous publications have suggested that there may be a link between bone metabolism alterations and HIV infection. The early bone loss seen in these patients was initially attributed to the use of highly active antiretroviral treatment (HAART) that included protease inhibitors. Recent studies, however, have suggested that it may be a direct consequence of the viral infection on bone metabolism, persistent activation of pro-inflammatory cytokines (TNFa), or altered vitamin D metabolism secondary to the virus, combined with subsequent factors (e.g., antiretroviral treatment) that aggravate the bone demineralization. We present an antiretroviral-naive 6-year-old girl with vertically transmitted HIV infection who presented with severe osteoporosis and multiple pathological fractures of the vertebrae, ribs, and upper and lower limbs. The child was treated with HAART, appropriate nutritional support for her age, physiotherapy and rehabilitation, calcium and vitamin D supplements, and alendronate therapy. After 6 weeks of treatment, the intense pain and muscle atrophy had disappeared and she was able to walk unassisted. At 6 months, bone mass had increased by 72%. The interest of this case lies in the presence of severe osteoporosis and multiple pathological fractures in an HIVinfected naive child. To date, this condition has only been described in patients treated with antiretrovirals. Moreover, this is the first reported HIV-positive pediatric patient treated with bisphosphonates, which proved to be highly successful.

  6. Novel Combination Treatments in Multiple Myeloma.

    PubMed

    Nooka, Ajay K; Lonial, Sagar

    2016-05-01

    The last decade has witnessed the identification of several novel druggable targets in multiple myeloma, leading to identification of novel therapies with clinically proven efficacy, both in the newly diagnosed and relapsed setting. More importantly, a common theme of good outcomes was observed among prospective randomized studies that have utilized combinations of agents with different mechanisms of action. The correlation between achieving a deeper response and the improvement in progression-free survival and overall survival has never been so clear. In this article, we elucidate the rationale for use of novel drug combinations in patients with myeloma, and review current evidence-based data supporting the use of specific combinations in various settings. We also attempt to craft a framework to guide clinicians in optimizing the use of combination therapies, to enable patients to derive maximal benefit. PMID:27188677

  7. Human immunodeficiency virus (HIV) modulates the associations between insulin resistance and cognition in the current combination antiretroviral therapy (cART) era: a study of the Women's Interagency HIV Study (WIHS).

    PubMed

    Valcour, Victor; Rubin, Leah H; Tien, Phyllis; Anastos, Kathryn; Young, Mary; Mack, Wendy; Cohen, Mardge; Golub, Elizabeth T; Crystal, Howard; Maki, Pauline M

    2015-08-01

    Cognitive impairment (CI) remains common despite access to combination antiretroviral therapy (cART); it has been linked to HIV-specific, HIV-related, and HIV-unrelated factors. Insulin resistance (IR) was associated with CI in the early cART era, when antiretroviral medications had greater mitochondrial and metabolic toxicity. We sought to examine these relationships in the current cART era of reduced antiretroviral toxicities. This study examined IR among non-diabetics in relation to a 1-h neuropsychological test battery among 994 women (659 HIV-infected and 335 HIV-uninfected controls) assessed between 2009 and 2011. The mean (standard deviation (SD)) age of the sample was 45.1 (9.3) years. The HIV-infected sample had a median interquartile range (IQR) cluster of differentiation 4 (CD4) T-lymphocyte count of 502 (310-727) cells/μL, and 54 % had undetectable plasma HIV RNA levels. Among all, the homeostasis model assessment (HOMA) of IR ranged from 0.25 to 37.14. In adjusted models, increasing HOMA was significantly associated with reduced performance on Letter-Number Sequencing (LNS) attention task (β = -0.10, p < 0.01) and on Hopkins Verbal Learning Test (HVLT) recognition (β = -0.10, p < 0.01) with weaker but statistically significant associations on phonemic fluency (β = -0.09, p = 0.01). An HIV*HOMA interaction effect was identified on the LNS attention task and Stroop trials 1 and 2, with worse performance in HIV-infected vs. HIV-uninfected women. In separate analyses, cohort members who had diabetes mellitus (DM) performed worse on the grooved pegboard test of psychomotor speed and manual dexterity. These findings confirm associations between both IR and DM on some neuropsychological tests and identify an interaction between HIV status and IR. PMID:25740539

  8. [A method for the combined treatment of chronic cystic sinusitis].

    PubMed

    Svatko, L G; Krasnozhen, V N; Pokrovskaia, E M

    2008-01-01

    A pathogenetically substantiated method is proposed for the combined treatment of chronic cystic sinusitis that includes sparing surgical intervention and postoperative treatment with ximedone, a regenerator drug with immunotropic activity. PMID:19156109

  9. "Conditional scholarships" for HIV/AIDS health workers: educating and retaining the workforce to provide antiretroviral treatment in sub-Saharan Africa.

    PubMed

    Bärnighausen, Till; Bloom, David E

    2009-02-01

    Without large increases in the number of health workers to treat HIV/AIDS (HAHW) many countries in sub-Saharan Africa will be unable to achieve universal coverage with antiretroviral treatment (ART), leading to large numbers of avoidable deaths among people living with HIV/AIDS. We conduct a cost-benefit analysis of a health care education scholarship that is conditional on the recipient committing to work for several years after graduation delivering ART in sub-Saharan Africa. Such a scholarship could address two of the main reasons for the low numbers of health workers in sub-Saharan Africa: low education rates and high emigration rates. We use Markov Monte Carlo microsimulation to estimate the expected net present value (eNPV) of "conditional scholarships" in sub-Saharan Africa. The scholarships are highly eNPV-positive under a wide range of assumptions. Conditional scholarships for a HAHW team sufficient to provide ART for 500 patients have an eNPV of 1.24 million year-2000 US dollars, assuming that the scholarship recipients are in addition to the health workers who would have been educated without scholarships and that the scholarships reduce annual HAHW emigration probabilities from 15% to 5% for five years. The eNPV of the education effect of the scholarships is larger than eNPV of the migration effect. Policy makers should consider implementing "conditional scholarships" for HAHW, especially in countries where health worker education capacity is currently underutilized or can be rapidly expanded.

  10. How acceptable are antiretrovirals for the prevention of sexually transmitted HIV?: A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention.

    PubMed

    Young, Ingrid; McDaid, Lisa

    2014-02-01

    Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence. PMID:23897125

  11. Access to antiretroviral treatment, issues of well-being and public health governance in Chad: what justifies the limited success of the universal access policy?

    PubMed Central

    2013-01-01

    Universal access to antiretroviral treatment (ART) in Chad was officially declared in December 2006. This presidential initiative was and is still funded 100% by the country’s budget and external donors’ financial support. Many factors have triggered the spread of AIDS. Some of these factors include the existence of norms and beliefs that create or increase exposure, the low-level education that precludes access to health information, social unrest, and population migration to areas of high economic opportunities and gender-based discrimination. Social forces that influence the distribution of dimensions of well-being and shape risks for infection also determine the persistence of access barriers to ART. The universal access policy is quite revolutionary but should be informed by the systemic barriers to access so as to promote equity. It is not enough to distribute ARVs and provide health services when health systems are poorly organized and managed. Comprehensive access to ART raises many organizational, ethical and policy problems that need to be solved to achieve equity in access. This paper argues that the persistence of access barriers is due to weak health systems and a poor public health leadership. AIDS has challenged health systems in a manner that is essentially different from other health problems. PMID:23902732

  12. Access to antiretroviral treatment, issues of well-being and public health governance in Chad: what justifies the limited success of the universal access policy?

    PubMed

    Azétsop, Jacquineau; Diop, Blondin A

    2013-01-01

    Universal access to antiretroviral treatment (ART) in Chad was officially declared in December 2006. This presidential initiative was and is still funded 100% by the country's budget and external donors' financial support. Many factors have triggered the spread of AIDS. Some of these factors include the existence of norms and beliefs that create or increase exposure, the low-level education that precludes access to health information, social unrest, and population migration to areas of high economic opportunities and gender-based discrimination. Social forces that influence the distribution of dimensions of well-being and shape risks for infection also determine the persistence of access barriers to ART. The universal access policy is quite revolutionary but should be informed by the systemic barriers to access so as to promote equity. It is not enough to distribute ARVs and provide health services when health systems are poorly organized and managed. Comprehensive access to ART raises many organizational, ethical and policy problems that need to be solved to achieve equity in access. This paper argues that the persistence of access barriers is due to weak health systems and a poor public health leadership. AIDS has challenged health systems in a manner that is essentially different from other health problems. PMID:23902732

  13. Behavioral Intervention Improves Treatment Outcomes Among HIV-Infected Individuals Who Have Delayed, Declined, or Discontinued Antiretroviral Therapy: A Randomized Controlled Trial of a Novel Intervention

    PubMed Central

    Cleland, Charles M.; Applegate, Elizabeth; Belkin, Mindy; Gandhi, Monica; Salomon, Nadim; Banfield, Angela; Leonard, Noelle; Riedel, Marion; Wolfe, Hannah; Pickens, Isaiah; Bolger, Kelly; Bowens, DeShannon; Perlman, David; Mildvan, Donna

    2015-01-01

    Nationally up to 60 % of persons living with HIV are neither taking antiretroviral therapy (ART) nor well engaged in HIV care, mainly racial/ethnic minorities. This study examined a new culturally targeted multi-component intervention to address emotional, attitudinal, and social/structural barriers to ART initiation and HIV care. Participants (N = 95) were African American/Black and Latino adults with CD4<500 cells/mm3 not taking ART, randomized 1:1 to intervention or control arms, the latter receiving treatment as usual. Primary endpoints were adherence, evaluated via ART concentrations in hair samples, and HIV viral load suppression. The intervention was feasible and acceptable. Eight months post-baseline, intervention participants tended to be more likely to evidence “good” (that is, 7 days/week) adherence (60 vs. 26.7 %; p = 0.087; OR = 3.95), and had lower viral load levels than controls (t(22) = 2.29, p = 0.032; OR = 5.20), both large effect sizes. This highly promising intervention merits further study. PMID:25835462

  14. Access to antiretroviral treatment, issues of well-being and public health governance in Chad: what justifies the limited success of the universal access policy?

    PubMed

    Azétsop, Jacquineau; Diop, Blondin A

    2013-08-01

    Universal access to antiretroviral treatment (ART) in Chad was officially declared in December 2006. This presidential initiative was and is still funded 100% by the country's budget and external donors' financial support. Many factors have triggered the spread of AIDS. Some of these factors include the existence of norms and beliefs that create or increase exposure, the low-level education that precludes access to health information, social unrest, and population migration to areas of high economic opportunities and gender-based discrimination. Social forces that influence the distribution of dimensions of well-being and shape risks for infection also determine the persistence of access barriers to ART. The universal access policy is quite revolutionary but should be informed by the systemic barriers to access so as to promote equity. It is not enough to distribute ARVs and provide health services when health systems are poorly organized and managed. Comprehensive access to ART raises many organizational, ethical and policy problems that need to be solved to achieve equity in access. This paper argues that the persistence of access barriers is due to weak health systems and a poor public health leadership. AIDS has challenged health systems in a manner that is essentially different from other health problems.

  15. Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naïve patients initiated on a three- or four-drug antiretroviral regimen including lamivudine.

    PubMed

    Bergroth, Tobias; Ekici, Halime; Gisslén, Magnus; Loes, Sabine Kinloch-de; Goh, Li-Ean; Freedman, Andrew; Lampe, Fiona; Johnson, Margaret A; Sönnerborg, Anders

    2009-01-01

    Therapy failure due to drug resistance development is a common phenomenon in HIV-infected patients. However, when the drug pressure leads to the earliest selection of drug-resistant HIV-1 populations is still unclear. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naïve HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment-naïve patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method. Among quadruple ART patients, who all were treated at primary HIV-1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild-type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four-drug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine + PI or PI/r containing ART given to treatment-naïve adherent patients is potent enough to prevent development of resistance during the first months of therapy.

  16. Role of CD8(+) lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment.

    PubMed

    Lifson, J D; Rossio, J L; Piatak, M; Parks, T; Li, L; Kiser, R; Coalter, V; Fisher, B; Flynn, B M; Czajak, S; Hirsch, V M; Reimann, K A; Schmitz, J E; Ghrayeb, J; Bischofberger, N; Nowak, M A; Desrosiers, R C; Wodarz, D

    2001-11-01

    Transient antiretroviral treatment with tenofovir, (R)-9-(2-phosphonylmethoxypropyl)adenine, begun shortly after inoculation of rhesus macaques with the highly pathogenic simian immunodeficiency virus (SIV) isolate SIVsmE660, facilitated the development of SIV-specific lymphoproliferative responses and sustained effective control of the infection following drug discontinuation. Animals that controlled plasma viremia following transient postinoculation treatment showed substantial resistance to subsequent intravenous rechallenge with homologous (SIVsmE660) and highly heterologous (SIVmac239) SIV isolates, up to more than 1 year later, despite the absence of measurable neutralizing antibody. In some instances, resistance to rechallenge was observed despite the absence of detectable SIV-specific binding antibody and in the face of SIV lymphoproliferative responses that were low or undetectable at the time of challenge. In vivo monoclonal antibody depletion experiments demonstrated a critical role for CD8(+) lymphocytes in the control of viral replication; plasma viremia rose by as much as five log units after depletion of CD8(+) cells and returned to predepletion levels (as low as <100 copy Eq/ml) as circulating CD8(+) cells were restored. The extent of host control of replication of highly pathogenic SIV strains and the level of resistance to heterologous rechallenge achieved following transient postinoculation treatment compared favorably to the results seen after SIVsmE660 and SIVmac239 challenge with many vaccine strategies. This impressive control of viral replication was observed despite comparatively modest measured immune responses, less than those often achieved with vaccination regimens. The results help establish the underlying feasibility of efforts to develop vaccines for the prevention of AIDS, although the exact nature of the protective host responses involved remains to be elucidated.

  17. Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders

    PubMed Central

    Pop-Eleches, Cristian; Thirumurthy, Harsha; Habyarimana, James P.; Zivin, Joshua G.; Goldstein, Markus P.; de Walque, Damien; MacKeen, Leslie; Haberer, Jessica; Kimaiyo, Sylvester; Sidle, John; Ngare, Duncan; Bangsberg, David R.

    2013-01-01

    Objective There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya. Design A randomized controlled trial of four SMS reminder interventions with 48 weeks of follow-up. Methods Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and randomly assigned to a control group or one of the four intervention groups. Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency. Adherence was measured using the medication event monitoring system. The primary outcome was whether adherence exceeded 90% during each 12-week period of analysis and the 48-week study period. The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results In intention-to-treat analysis, 53% of participants receiving weekly SMS reminders achieved adherence of at least 90% during the 48 weeks of the study, compared with 40% of participants in the control group (P=0.03). Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group (81 vs. 90%, P = 0.03). Conclusion These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings. PMID:21252632

  18. The Effects of Opioid Substitution Treatment and Highly Active Antiretroviral Therapy on the Cause-Specific Risk of Mortality Among HIV-Positive People Who Inject Drugs

    PubMed Central

    Nosyk, Bohdan; Min, Jeong E.; Evans, Elizabeth; Li, Libo; Liu, Lei; Lima, Viviane D.; Wood, Evan; Montaner, Julio S. G.

    2015-01-01

    Background. Prior studies indicated opioid substitution treatment (OST) reduces mortality risk and improves the odds of accessing highly active antiretroviral therapy (HAART); however, the relative effects of these treatments for human immunodeficiency virus (HIV)–positive people who inject drugs (PWID) are unclear. We determine the independent and joint effects of OST and HAART on mortality, by cause, within a population of HIV-positive PWID initiating HAART. Methods. Using a linked population-level database for British Columbia, Canada, we used time-to-event analytic methods, including competing risks models, proportional hazards models with time-varying covariates, and marginal structural models, to identify the independent and joint effects of OST and HAART on all-cause as well as drug- and HIV-related mortality, controlling for covariates. Results. Among 1727 HIV-positive PWID, 493 (28.5%) died during a median 5.1 years (interquartile range, 2.1–9.1) of follow-up: 18.7% due to drug-related causes, 55.8% due to HIV-related causes, and 25.6% due to other causes. Standardized mortality ratios were 12.2 (95% confidence interval [CI], 9.8, 15.0) during OST and 30.0 (27.1, 33.1) during periods out of OST. Both OST (adjusted hazard, 0.34; 95% CI, .23, .49) and HAART (0.39 [0.31, 0.48]) decreased the hazard of all-cause mortality; however, individuals were at lowest risk of death when these medications were used jointly (0.16 [0.10, 0.26]). Both OST and HAART independently protected against HIV-related death, drug-related death and death due to other causes. Conclusions. While both OST and HAART are life-saving treatments, joint administration is urgently needed to protect against both drug- and HIV-related mortality. PMID:26113656

  19. nViremia and drug resistance among HIV-1 patients on antiretroviral treatment – a cross-sectional study in Soweto, South Africa

    PubMed Central

    El-Khatib, Ziad; Ekström, Anna Mia; Ledwaba, Johanna; Mohapi, Lerato; Laher, Fatima; Karstaedt, Alan; Charalambous, Salome; Petzold, Max; Katzenstein, David; Morris, Lynn

    2010-01-01

    Background: We assessed risk factors for viremia and drug resistance (DR) among long-term recipients of antiretroviral therapy (ART) in South Africa. Methods: In 2008, we conducted a cross-sectional study among patients receiving ART for ≥12 months. Genotypic resistance testing was performed on individuals with a viral load >400 RNA copies/ml. Multiple logistic regression analysis was used to assess associations. Results: Of 998 subjects, 75% were women with a median age of 41. Most (64%) had been on treatment for >3 years. The prevalence of viremia was 14% (n=139); 12% (102/883) on first-line (i.e. NNRTI based regimen) and 33% (37/115) on second-line (i.e. PI based regimen) ART. Of viremic patients, 78% had DR mutations. For NRTIs, NNRTIs and PIs the prevalence of mutations was 64%, 81% and 2% among first-line and 29%, 54% and 6% among second-line failures respectively. M184V/I, K103N and V106A/M were the most common mutations. Significant risk factors associated with viremia on first-line included concurrent tuberculosis treatment (OR 6.4, 2.2-18.8, p<0.01) and a recent history of poor adherence (OR 2.7, 1.3-5.6, p=0.01). Among second-line failures, attending a public clinic (OR 4.6, 1.8-11.3, p<0.01) and not having a refrigerator at home (OR 6.7, 1.2-37.5, p=0.03) were risk factors for virological failure. Conclusions: Risk factors for viral failure were line-regimen dependent. Second-line ART recipients had a higher rate of viremia, albeit with infrequent PI DR mutations. Measures to maintain effective virologic suppression should include increased adherence counseling, attention to concomitant tuberculosis treatment and heat-stable formulations of second-line ART regimens. PMID:20453629

  20. Antiretroviral treatment sequencing strategies to overcome HIV type 1 drug resistance in adolescents and adults in low-middle-income countries.

    PubMed

    De Luca, Andrea; Hamers, Raphael L; Schapiro, Jonathan M

    2013-06-15

    Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success. PMID:23687291

  1. [Effectiveness of combined treatment of infective endocarditis].

    PubMed

    Nikolaevskiĭ, E N; Khubulava, G G; Osadchuk, M A

    2006-01-01

    The purpose of the study was to develop and perfect complex therapy of modern infective endocarditis (IE). Ten-year experience in clinical diagnostics of 240 patients with acute, subacute, and lingering IE was summarized; the effectiveness of their treatment was evaluated. The features of modern IE were acute and subacute course of the disease with the involvement of aortal (37.8% of cases), tricuspid (16.8%), mitral (15.2%) valve, and septicemia, caused by highly virulent microflora (staphylococci--51% of cases; gram-negative bacteria--13%; fungi--5%). The clinical manifestations of modern IE included toxic infectious syndrome (24% of cases), heart failure (21%), symptoms of complications (16%), central hemodynamics disturbances (12%), and splenomegaly (8%). The treatment included antibacterial, pathogenetic, and symptomatic therapy, as well as extracorporal hemocorrection and cardiosurgery. Analysis of the results of surgical treatment of 140 IE patients allowed development of indications for valve prosthesis. PMID:16512400

  2. [Severe or life-threatening interactions between antiretrovirals and non-HIV drugs].

    PubMed

    Manzardo, Christian; Tuset, Montserrat; Miró, Jose M; Gatell, Jose M

    2015-01-01

    Highly active antiretroviral therapy has helped to improved control of the HIV infection, and has led to a progressively older population with the infection having a life expectancy quite similar to that of the general population. On the other hand, it is also known that HIV infection, even in patients with undetectable viral loads and good immunity, carries an increased cardiovascular risk, as well as an increased incidence of certain cancers. Therefore, the majority of HIV-infected patients receive several drugs (either prescribed by the physician or self-administered) combined with antiretrovirals. This article reviews the interactions between antiretrovirals and other drugs that can cause significant damage to patients, or even be life-threatening and of whom clinicians, especially those not directly treating HIV-infected patients, should be aware. A review is also presented on the implications of interactions between antiretrovirals and other drugs in special situations, such as the co-administration with cytostatics, immunesuppressants used in solid organ transplantation, or patients receiving new treatments for hepatitisC. Generally, combinations with two nucleos(t)ide reverse transcriptase inhibitors and raltegravir (or in the near future, dolutegravir) are those with less potential for clinically significant interactions. PMID:24913990

  3. Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study

    PubMed Central

    Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

    2016-01-01

    Background: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. Objective: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. Methods: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Results: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. Conclusions: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function. PMID:26899539

  4. Treatment outcomes of HIV-positive patients on first-line antiretroviral therapy in private versus public HIV clinics in Johannesburg, South Africa

    PubMed Central

    Moyo, Faith; Chasela, Charles; Brennan, Alana T; Ebrahim, Osman; Sanne, Ian M; Long, Lawrence; Evans, Denise

    2016-01-01

    Background Despite the widely documented success of antiretroviral therapy (ART), stakeholders continue to face the challenges of poor HIV treatment outcomes. While many studies have investigated patient-level causes of poor treatment outcomes, data on the effect of health systems on ART outcomes are scarce. Objective We compare treatment outcomes among patients receiving HIV care and treatment at a public and private HIV clinic in Johannesburg, South Africa. Patients and methods This was a retrospective cohort analysis of ART naïve adults (≥18.0 years), initiating ART at a public or private clinic in Johannesburg between July 01, 2007 and December 31, 2012. Cox proportional-hazards regression was used to identify baseline predictors of mortality and loss to follow-up (>3 months late for the last scheduled visit). Generalized estimating equations were used to determine predictors of failure to suppress viral load (≥400 copies/mL) while the Wilcoxon rank-sum test was used to compare the median absolute change in CD4 count from baseline to 12 months post-ART initiation. Results 12,865 patients initiated ART at the public clinic compared to 610 at the private clinic. The patients were similar in terms of sex and age at initiation. Compared to public clinic patients, private clinic patients initiated ART at higher median CD4 counts (159 vs 113 cells/mm3) and World Health Organization stage I/II (76.1% vs 58.5%). Adjusted hazard models showed that compared to public clinic patients, private clinic patients were less likely to die (adjusted hazard ratio [aHR] 0.50; 95% confidence interval [CI] 0.35–0.70) but were at increased risk of loss to follow-up (aHR 1.80; 95% CI 1.59–2.03). By 12 months post-ART initiation, private clinic patients were less likely to have a detectable viral load (adjusted relative risk 0.65; 95% CI 0.49–0.88) and recorded higher median CD4 change from baseline (184 cells/mm3 interquartile range 101–300 vs 158 cells/mm3 interquartile

  5. Transmitted Drug Resistance and Antiretroviral Treatment Outcomes in Non-Subtype B HIV1- Infected Patients in South East Asia

    PubMed Central

    Phanuphak, Praphan; Sirivichayakul, Sunee; Jiamsakul, Awachana; Sungkanuparph, Somnuek; Kumarasamy, Nagalingeswaran; Lee, Man Po; Sirisanthana, Thira; Kantipong, Pacharee; Lee, Christopher; Kamarulzaman, Adeeba; Mustafa, Mahiran; Ditangco, Rossana; Merati, Tuti; Ratanasuwan, Winai; Singtoroj, Thida; Kantor, Rami

    2014-01-01

    Background We compared treatment outcomes of transmitted drug resistance (TDR) in patients on fully or partially sensitive drug regimens. Methods Factors associated with survival and failure were analyzed using Cox proportional hazards and discrete time conditional logistic models. Results TDR, found in 60/1471 (4.1%) Asian treatment naïve patients, was one of the significant predictors of failure. Patients with TDR to >1 drug in their regimen were >3 times as likely to fail compared to no TDR. Conclusion TDR was associated with failure in the context of non-fully sensitive regimens. Efforts are needed to incorporate resistance testing into national treatment programs. PMID:24413039

  6. Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection.

    PubMed

    Ahmad, Fareed; Tufa, Dejene Milkessa; Mishra, Neha; Jacobs, Roland; Schmidt, Reinhold E

    2015-12-01

    HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART.

  7. Managing antiretroviral-associated liver disease.

    PubMed

    Dieterich, Douglas

    2003-09-01

    The use of all potent drugs is associated with toxicities and antiretroviral (ARV) drugs are no exception. Antiretroviral therapy-associated hepatic toxicity is of increasing concern in the management of patients with HIV/AIDS. Liver toxicity has been reported in some HIV-infected patients being treated with drugs from all of these classes of ARV drugs: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although the majority of cases involve asymptomatic elevations of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), severe, and, in a minority of cases, life threatening, liver disease has been reported in patients treated with ARV drugs. The exact causes of elevated plasma levels of AST and ALT are complex and, in many cases, obscure. The combination of viral hepatic disease, drugs that act adversely directly on the liver and drugs that act on other systems of the body which in turn, adversely affect the liver, can result in hepatic toxicity. Such toxicity may be inappropriately attributed solely to the direct effect of a drug. Knowledge of the possible causes of liver toxicity, and ways to avoid it, should reduce the risk of developing hepatotoxicity. The physician's task is to prevent the development of liver toxicity, e.g., by choosing appropriate therapeutic regimens and by careful management of the patient. This involves frequent monitoring of the patient, both clinically and by utilizing liver function tests on a regular basis. If signs and symptoms of liver disease do develop, prompt and expert management is essential. This review discusses the influence of a number of factors on hepatic toxicity including viral hepatitis, insulin resistance and the specific ARV drugs used in the treatment of patients with HIV/AIDS.

  8. The RADAR Study: Week 48 Safety and Efficacy of RAltegravir Combined with Boosted DARunavir Compared to Tenofovir/Emtricitabine Combined with Boosted Darunavir in Antiretroviral-Naive Patients. Impact on Bone Health

    PubMed Central

    Bedimo, Roger J.; Drechsler, Henning; Jain, Mamta; Cutrell, James; Zhang, Song; Li, Xilong; Farukhi, Irfan; Castanon, Rosinda; Tebas, Pablo; Maalouf, Naim M.

    2014-01-01

    Background NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression. Methods In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48. Results Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (−0.25 vs. −0.71 mg/dL (p = 0.270), and eGFR (−4.4 vs. −7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. −7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = −0.394, p = 0.003 for CTX; and R = −0.477, p<0.001 for P1NP). Conclusion The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health. Trial Registration ClinicalTrials.gov NCT 00677300 PMID:25170938

  9. Evidence for Adverse Phonatory Change Following an Inhaled Combination Treatment

    ERIC Educational Resources Information Center

    Erickson, Elizabeth; Sivasankar, Mahalakshmi

    2010-01-01

    Purpose: Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE),…

  10. Treatment for Krabbe's disease: Finding the combination.

    PubMed

    Mikulka, Christina R; Sands, Mark S

    2016-11-01

    Globoid cell leukodystrophy (GLD) is an autosomal recessive neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactocerebrosidase (GALC). GALC is responsible for catabolism of certain glycolipids, including the toxic compound galactosylsphingosine (psychosine). Histological signs of disease include the widespread loss of myelin in the central and peripheral nervous systems, profound neruroinflammation, and axonal degeneration. Patients suffering from GLD also display neurological deterioration. Many different individual therapies have been investigated in the murine model of the GLD, the Twitcher mouse, with minimal success. The current standard of care for GLD patients, hematopoietic stem cell transplantation, serves only to delay disease progression and is not an effective cure. However, combination therapies that target different pathogenic mechanisms/pathways have been more effective at reducing histological signs of disease, delaying disease onset, prolonging life span, and improving behavioral/cognitive functions in rodent models of Krabbe's disease. In some cases, dramatic synergy between the various therapies has been observed. © 2016 Wiley Periodicals, Inc. PMID:27638598

  11. Hyperthermia in combined treatment of cancer.

    PubMed

    Wust, P; Hildebrandt, B; Sreenivasa, G; Rau, B; Gellermann, J; Riess, H; Felix, R; Schlag, P M

    2002-08-01

    Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.

  12. Increasing HIV-1 pretreatment drug resistance among antiretroviral-naïve adults initiating treatment between 2006 and 2014 in Nairobi, Kenya.

    PubMed

    Chung, Michael H; Silverman, Rachel; Beck, Ingrid A; Yatich, Nelly; Dross, Sandra; McKernan-Mullin, Jennifer; Bii, Stephen; Tapia, Kenneth; Stern, Joshua; Chohan, Bhavna; Sakr, Samah R; Kiarie, James N; Frenkel, Lisa M

    2016-06-19

    Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006. PMID:27058353

  13. CD4 Counts at Entry to HIV Care in Mexico for Patients under the "Universal Antiretroviral Treatment Program for the Uninsured Population," 2007-2014.

    PubMed

    Hernández-Romieu, Alfonso C; del Rio, Carlos; Hernández-Ávila, Juan Eugenio; Lopez-Gatell, Hugo; Izazola-Licea, José Antonio; Uribe Zúñiga, Patricia; Hernández-Ávila, Mauricio

    2016-01-01

    In Mexico, public health services have provided universal access to antiretroviral therapy (ART) since 2004. For individuals receiving HIV care in public healthcare facilities, the data are limited regarding CD4 T-lymphocyte counts (CD4e) at the time of entry into care. Relevant population-based estimates of CD4e are needed to inform strategies to maximize the impact of Mexico's national ART program, and may be applicable to other countries implementing universal HIV treatment programs. For this study, we retrospectively analyzed the CD4e of persons living with HIV and receiving care at state public health facilities from 2007 to 2014, comparing CD4e by demographic characteristics and the marginalization index of the state where treatment was provided, and assessing trends in CD4e over time. Our sample included 66,947 individuals who entered into HIV care between 2007 and 2014, of whom 79% were male. During the study period, the male-to-female ratio increased from 3.0 to 4.3, reflecting the country's HIV epidemic; the median age at entry decreased from 34 years to 32 years. Overall, 48.6% of individuals entered care with a CD4≤200 cells/μl, ranging from 42.2% in states with a very low marginalization index to 52.8% in states with a high marginalization index, and from 38.9% among individuals aged 18-29 to 56.5% among those older than 50. The adjusted geometric mean (95% confidence interval) CD4e increased among males from 135 (131,142) cells/μl in 2007 to 148 (143,155) cells/μl in 2014 (p-value<0.0001); no change was observed among women, with a geometric mean of 178 (171,186) and 171 (165,183) in 2007 and 2014, respectively. There have been important gains in access to HIV care and treatment; however, late entry into care remains an important barrier in achieving optimal outcomes of ART in Mexico. The geographic, socioeconomic, and demographic differences observed reflect important inequities in timely access to HIV prevention, care, and treatment services

  14. CD4 Counts at Entry to HIV Care in Mexico for Patients under the "Universal Antiretroviral Treatment Program for the Uninsured Population," 2007-2014.

    PubMed

    Hernández-Romieu, Alfonso C; del Rio, Carlos; Hernández-Ávila, Juan Eugenio; Lopez-Gatell, Hugo; Izazola-Licea, José Antonio; Uribe Zúñiga, Patricia; Hernández-Ávila, Mauricio

    2016-01-01

    In Mexico, public health services have provided universal access to antiretroviral therapy (ART) since 2004. For individuals receiving HIV care in public healthcare facilities, the data are limited regarding CD4 T-lymphocyte counts (CD4e) at the time of entry into care. Relevant population-based estimates of CD4e are needed to inform strategies to maximize the impact of Mexico's national ART program, and may be applicable to other countries implementing universal HIV treatment programs. For this study, we retrospectively analyzed the CD4e of persons living with HIV and receiving care at state public health facilities from 2007 to 2014, comparing CD4e by demographic characteristics and the marginalization index of the state where treatment was provided, and assessing trends in CD4e over time. Our sample included 66,947 individuals who entered into HIV care between 2007 and 2014, of whom 79% were male. During the study period, the male-to-female ratio increased from 3.0 to 4.3, reflecting the country's HIV epidemic; the median age at entry decreased from 34 years to 32 years. Overall, 48.6% of individuals entered care with a CD4≤200 cells/μl, ranging from 42.2% in states with a very low marginalization index to 52.8% in states with a high marginalization index, and from 38.9% among individuals aged 18-29 to 56.5% among those older than 50. The adjusted geometric mean (95% confidence interval) CD4e increased among males from 135 (131,142) cells/μl in 2007 to 148 (143,155) cells/μl in 2014 (p-value<0.0001); no change was observed among women, with a geometric mean of 178 (171,186) and 171 (165,183) in 2007 and 2014, respectively. There have been important gains in access to HIV care and treatment; however, late entry into care remains an important barrier in achieving optimal outcomes of ART in Mexico. The geographic, socioeconomic, and demographic differences observed reflect important inequities in timely access to HIV prevention, care, and treatment services

  15. Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya

    PubMed Central

    Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

    2016-01-01

    Introduction Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. Methods We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients’ characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Results Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. Conclusions In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment

  16. Use, perceptions, and acceptability of a ready-to-use supplementary food among adult HIV patients initiating antiretroviral treatment: a qualitative study in Ethiopia

    PubMed Central

    Olsen, Mette Frahm; Tesfaye, Markos; Kaestel, Pernille; Friis, Henrik; Holm, Lotte

    2013-01-01

    Objectives Ready-to-use supplementary foods (RUSF) are used increasingly in human immunodeficiency virus (HIV) programs, but little is known about how it is used and viewed by patients. We used qualitative methods to explore the use, perceptions, and acceptability of RUSF among adult HIV patients in Jimma, Ethiopia. Methods The study obtained data from direct observations and 24 in-depth interviews with HIV patients receiving RUSF. Results Participants were generally very motivated to take RUSF and viewed it as beneficial. RUSF was described as a means to fill a nutritional gap, to “rebuild the body,” and protect it from harmful effects of antiretroviral treatment (ART). Many experienced nausea and vomiting when starting the supplement. This caused some to stop supplementation, but the majority adapted to RUSF. The supplement was eaten separately from meal situations and only had a little influence on household food practices. RUSF was described as food with “medicinal qualities,” which meant that many social and religious conventions related to food did not apply to it. The main concerns about RUSF related to the risk of HIV disclosure and its social consequences. Conclusion HIV patients view RUSF in a context of competing livelihood needs. RUSF intake was motivated by a strong wish to get well, while the risk of HIV disclosure caused concerns. Despite the motivation for improving health, the preservation of social networks was prioritized, and nondisclosure was often a necessary strategy. Food sharing and religious fasting practices were not barriers to the acceptability of RUSF. This study highlights the importance of ensuring that supplementation strategies, like other HIV services, are compatible with the sociocultural context of patients. PMID:23766634

  17. Using an innovative mixed method methodology to investigate the appropriateness of a quantitative instrument in an African context: Antiretroviral treatment and quality of life.

    PubMed

    Greeff, Minrie; Chepuka, Lignet M; Chilemba, Winnie; Chimwaza, Angela F; Kululanga, Lucy I; Kgositau, Mabedi; Manyedi, Eva; Shaibu, Sheila; Wright, Susan C D

    2014-01-01

    The relationship between quality of life (QoL) and antiretroviral treatment (ART) has mainly been studied using quantitative scales often not appropriate for use in other contexts and without taking peoples' lived experiences into consideration. Sub-Saharan Africa has the highest incidence of HIV and AIDS yet there is paucity in research done on QoL. This research report is intended to give an account of the use of a mixed method convergent parallel design as a novice approach to evaluate an instrument's context specificity, appropriateness and usefulness in another context for which it was designed. Data were collected through a qualitative exploration of the experiences of QoL of people living with HIV or AIDS (PLHA) in Africa since being on ART, as well as the quantitative measurements obtained from the HIV/AIDS-targeted quality of life (HAT-QoL) instrument. This study was conducted in three African countries. Permission and ethical approval to conduct the study were obtained. Purposive voluntary sampling was used to recruit PLHA through mediators working in community-based HIV/AIDS organisations and health clinics. Interviews were analysed through open coding and the quantitative data through descriptive statistics and the Cronbach's alpha coefficient. A much wider range and richness of experiences were expressed than measured by the HAT-QoL instrument. Although an effective instrument for use in the USA, it was found not to be sensitive, appropriate and useful in an African context in its present form. The recommendations focus on adapting the instrument using the data from the in-depth interviews or to develop a context-sensitive instrument that could measure QoL of PLHA in Africa.

  18. Realist evaluation of the antiretroviral treatment adherence club programme in selected primary healthcare facilities in the metropolitan area of Western Cape Province, South Africa: a study protocol

    PubMed Central

    Mukumbang, Ferdinand C; Van Belle, Sara; Marchal, Bruno; Van Wyk, Brian

    2016-01-01

    Introduction Suboptimal retention in care and poor treatment adherence are key challenges to antiretroviral therapy (ART) in sub-Saharan Africa. Community-based approaches to HIV service delivery are recommended to improve patient retention in care and ART adherence. The implementation of the adherence clubs in the Western Cape province of South Africa was with variable success in terms of implementation and outcomes. The need for operational guidelines for its implementation has been identified. Therefore, understanding the contexts and mechanisms for successful implementation of the adherence clubs is crucial to inform the roll-out to the rest of South Africa. The protocol outlines an evaluation of adherence club intervention in selected primary healthcare facilities in the metropolitan area of the Western Cape Province, using the realist approach. Methods and analysis In the first phase, an exploratory study design will be used. Document review and key informant interviews will be used to elicit the programme theory. In phase two, a multiple case study design will be used to describe the adherence clubs in five contrastive sites. Semistructured interviews will be conducted with purposively selected programme implementers and members of the clubs to assess the context and mechanisms of the adherence clubs. For the programme's primary outcomes, a longitudinal retrospective cohort analysis will be conducted using routine patient data. Data analysis will involve classifying emerging themes using the context-mechanism-outcome (CMO) configuration, and refining the primary CMO configurations to conjectured CMO configurations. Finally, we will compare the conjectured CMO configurations from the cases with the initial programme theory. The final CMOs obtained will be translated into middle range theories. Ethics and dissemination The study will be conducted according to the principles of the declaration of Helsinki (1964). Ethics clearance was obtained from the

  19. Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era

    PubMed Central

    Lewden, Charlotte; Drabo, Youssoufou J; Zannou, Djimon M; Maiga, Moussa Y; Minta, Daouda K; Sow, Papa S; Akakpo, Jocelyn; Dabis, François; Eholié, Serge P

    2014-01-01

    Objective We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. Method We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. Results Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women), 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm3 (IQR: 25–177) and 48% had previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36%), cerebral toxoplasmosis (10%), cryptococcosis (9%) and sepsis (7%). Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. Conclusions AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease

  20. Risk Factors for Cervical Intraepithelial Neoplasia in HIV-Infected Women on Antiretroviral Treatment in Côte d'Ivoire, West Africa

    PubMed Central

    Jaquet, Antoine; Horo, Apollinaire; Ekouevi, Didier K.; Toure, Badian; Coffie, Patrick A.; Effi, Benjamin; Lenaud, Severin; Messou, Eugene; Minga, Albert; Sasco, Annie J.; Dabis, François

    2014-01-01

    Background Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance. Methods A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies. Results Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1–5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301–621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2–0.6) or ≥200–350 cells/mm3 (OR 0.6; 95% CI 0.4–1.0) (Ref: <200 cells/mm3 CD4) (p<10−4). Conclusions The presence of CIN+ is less common among HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out. PMID:24595037

  1. Barriers to free antiretroviral treatment access among kothi-identified men who have sex with men and aravanis (transgender women) in Chennai, India

    PubMed Central

    Chakrapani, Venkatesan; Shunmugam, Murali; Dubrow, Robert

    2011-01-01

    The Indian government provides free antiretroviral treatment (ART) for people living with HIV. To assist in developing policies and programs to advance equity in ART access, we explored barriers to ART access among kothis (men who have sex with men whose gender expression is feminine) and aravanis (transgender women, also known as hijras) living with HIV in Chennai. In the last quarter of 2007, we conducted six focus groups and four key-informant interviews. Data were explored using framework analysis to identify categories and derive themes. We identified barriers to ART access at the family/social-level, healthcare system-level, and individual-level; however we found these barriers to be highly interrelated. The primary individual-level barrier was integrally linked to the family/social and healthcare levels: many kothis and aravanis feared serious adverse consequences if their HIV-positive status were revealed to others. Strong motivations to keep one’s HIV-positive status and same-sex attraction secret were interconnected with sexual prejudice against MSM and transgenders, and HIV stigma prevalent in families, the healthcare system, and the larger society. HIV stigma was present within kothi and aravani communities as well. Consequences of disclosure, including rejection by family, eviction from home, social isolation, loss of subsistence income, and maltreatment (although improving) within the healthcare system, presented powerful disincentives to accessing ART. Given the multi-level barriers to ART access related to stigma and discrimination, interventions to facilitate ART uptake should address multiple constituencies: the general public, healthcare providers, and the kothi and aravani communities. India needs a national policy and action plan to address barriers to ART access at family/social, healthcare system, and individual levels for aravanis, kothis, other subgroups of men who have sex with men and other marginalized groups. PMID:22117127

  2. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals

    PubMed Central

    Blanco-Heredia, Juan; Lecanda, Aarón; Valenzuela-Ponce, Humberto; Brander, Christian; Ávila-Ríos, Santiago; Reyes-Terán, Gustavo

    2016-01-01

    Background Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART) efficacy and may be an integral part of future cure strategies. Methods We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR) positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations. Results Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64%) corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual) or DR (median 6 pairs/individual) were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001). While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient’s virus (mean 68% of cases), responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002). Conclusions Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides. PMID:26808823

  3. Exploring the patterns of use and the feasibility of using cellular phones for clinic appointment reminders and adherence messages in an antiretroviral treatment clinic, Durban, South Africa.

    PubMed

    Crankshaw, Tamaryn; Corless, Inge B; Giddy, Janet; Nicholas, Patrice K; Eichbaum, Quentin; Butler, Lisa M

    2010-11-01

    In preparation for a proposed intervention at an antiretroviral therapy (ART) clinic in Durban, South Africa, we explored the dynamics and patterns of cellular phone use among this population, in order to ascertain whether clinic contact via patients' cellular phones was a feasible and acceptable modality for appointment reminders and adherence messages. Adults, who were more than 18 years old, ambulatory, and who presented for treatment at the clinic between October-December 2007, were consecutively recruited until the sample size was reached (n = 300). A structured questionnaire was administered, including questions surrounding sociodemographics, cellular phone availability, patterns of use, and acceptability of clinic contact for the purpose of clinic appointment reminders and adherence support. Most respondents (n = 242; 81%) reported current ownership of a cellular phone with 95% utilizing a prepaid airtime service. Those participants who currently owned a cellular phone reported high cellular phone turnover due to theft or loss (n = 94, 39%) and/or damage (n = 68, 28%). More females than men switched their cell phones off during the day (p = 0.002) and were more likely to not take calls in certain social milieus (p ≤ 0.0001). Females were more likely to share their cell phone with others (p = 0.002) or leave it in a place where someone could access it (p = 0.005). Most respondents were willing to have clinic contact via their cellular phones, either verbally (99%) or via text messages (96%). The use of cellular phones for intervention purposes is feasible and should be further investigated. The findings highlight the value of gender-based analyses in informing interventions.

  4. Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambaréné, Gabon

    PubMed Central

    Janssen, Saskia; Hermans, Sabine; Knap, Martijn; Moekotte, Alma; Rossatanga, Elie G.; Adegnika, Akim A.; Bélard, Sabine; Hänscheid, Thomas; Grobusch, Martin P.

    2015-01-01

    Background Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections. Methodology and Principal Findings This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence. Conclusions/Significance CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established. PMID:25993501

  5. Implications of patent pools on innovation regarding antiretrovirals.

    PubMed

    Noehrenberg, Eric

    2010-01-19

    Patent pools have been promoted as an innovative means of promoting the production of fixed-dose combination antiretroviral medicines (ARVs), which can be particularly appropriate for resource-poor settings. An important question, however, is what are the implications of patent pools on innovation for creating new and improved antiretrovirals. Indeed, given the continuing mutation of HIV and growing resistance to existing treatments, continued innovation in ARV development is vital for addressing these challenges. Would patent pools be a hindrance or rather a stimulus for further innovation? This question is particularly relevant in light of UNITAID's initiative to create a patent pool for ARV development, focusing on pediatric formulations and new combinations, by the end of 2009. In this article, the author argues that a voluntary and well-designed patent pool, involving both innovative and generic manufacturers, focused on developing fixed-dose combinations for resource-poor markets with the greatest need, could actually stimulate increased innovation to meet these needs. Indeed, by bringing together the major ARV producers worldwide to collaborate on developing products which will meet the needs of the poorest, an ARV patent pool could create significant public health benefits. UNITAID has taken the lead in designing and implementing such a pool and UNITAID's experience will have important lessons for policy-makers in the future.

  6. Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy.

    PubMed

    Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V; Iser, David; Sasadeusz, Joe; Lewin, Sharon R

    2016-01-01

    Background.  Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods.  We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results.  The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions.  The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.

  7. Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment

    PubMed Central

    Bernasconi, Davide Paolo; Casari, Salvatore; Maggiolo, Franco; Cauda, Roberto; Di Pietro, Massimo; Ladisa, Nicoletta; Sighinolfi, Laura; Dal Zoppo, Sarah; Sabbatini, Francesca; Soria, Alessandro; Pezzoli, Chiara; Mondi, Annalisa; Costarelli, Silvia; Valsecchi, Maria Grazia; Torti, Carlo; Gori, Andrea

    2016-01-01

    Background Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear. Methods Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89–60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates). Results 2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2–3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8–2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4–6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF. Conclusions Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage. PMID:27632369

  8. Building adherence-competent communities: Factors promoting children's adherence to anti-retroviral HIV/AIDS treatment in rural Zimbabwe

    PubMed Central

    Campbell, Catherine; Skovdal, Morten; Mupambireyi, Zivai; Madanhire, Claudius; Nyamukapa, Constance; Gregson, Simon

    2012-01-01

    Given relatively high levels of adherence to HIV treatment in Africa, we explore factors facilitating children's adherence, despite poverty, social disruption and limited health infrastructure. Using interviews with 25 nurses and 40 guardians in Zimbabwe, we develop our conceptualisation of an ‘adherence competent community’, showing how members of five networks (children, guardians, community members, health workers and NGOs) have taken advantage of the gradual public normalisation of HIV/AIDS and improved drug and service availability to construct new norms of solidarity with HIV and AIDS sufferers, recognition of HIV-infected children's social worth, an ethic of care/assistance and a supporting atmosphere of enablement/empowerment. PMID:21975285

  9. Combination irradiation treatments for food safety and phytosanitary uses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Combination of irradiation treatment with other preservation techniques is of potential importance in enhancing the effectiveness and reducing the energy or dose requirement for destroying food borne illness and spoilage organisms while retaining or improving product quality. Phytosanitary irradiati...

  10. Hormonal effects on Tetrahymena: change in case of combined treatment.

    PubMed

    Csaba, G; Lajkó, Eszter; Pállinger, Eva

    2010-12-01

    In order to approach their natural conditions, populations of Tetrahymena were kept in Losina-Losinky's salt solution for 1 h, than in the tryptone+yeast medium. During this time they were treated with histamine, serotonin or insulin, or with the combinations of these hormones. Effect of the combined treatments on the production of serotonin (5HT), or adrenocorticotropic hormone (ACTH) or triiodothyronine (T₃) by the cells was compared to the effect of single-hormone treatments. Significant differences were seen between the results obtained following the single or combined treatments. There was no summation of the effects, however an elevation or diminution of the hormone production was observed after the combined treatment, as compared with the untreated controls or with the use of one of the hormones in the samples. The experiments demonstrate that there is a hormonal regulation between the Tetrahymena cells and the hormones influence each other's effect. PMID:21183424

  11. CROI 2016: Advances in Antiretroviral Therapy.

    PubMed

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID:27398863

  12. Progress in antiretroviral drug delivery using nanotechnology.

    PubMed

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-08-09

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease.

  13. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

  14. HIV Drug Resistance in Antiretroviral Treatment-Naïve Individuals in the Largest Public Hospital in Nicaragua, 2011-2015

    PubMed Central

    Tapia-Trejo, Daniela; Hernández-Álvarez, Bismarck F.; Moreira-López, Sumaya E.; Quant-Durán, Carlos J.; Porras-Cortés, Guillermo; Reyes-Terán, Gustavo

    2016-01-01

    Background Increasing HIV pre-treatment drug resistance (PDR) levels have been observed in regions with increasing antiretroviral treatment (ART) coverage. However, data is lacking for several low/middle-income countries. We present the first PDR survey in Nicaragua since ART introduction in the country in 2003. Methods HIV-infected, ART-naïve Nicaraguan individuals were enrolled at Roberto Calderón Hospital, the largest national HIV referral center, from 2011 to 2015. HIV pol sequences were obtained at a WHO-accredited laboratory in Mexico by Sanger and next generation sequencing (NGS). PDR was assessed using the WHO surveillance drug resistance mutation (SDRM) list and the Stanford HIVdb tool. Results 283 individuals were enrolled in the study. The overall PDR prevalence based on the list of SDRMs was 13.4%. Using the Stanford HIVdb tool, overall PDR reached 19.4%; with both nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) PDR levels independently reaching moderate levels (6.7% and 11.3% respectively). Protease inhibitor PDR was low (2.8%). Using NGS with 2% threshold to detect SDRMs, PDR increased to 25.3%. K103N and M41L were the most frequent SDRMs and were present mostly in proportions >20% in each individual. A significant temporal increase in NNRTI PDR was observed (p = 0.0422), with no apparent trends for other drug classes. Importantly, PDR to zidovudine + lamivudine + efavirenz and tenofovir + emtricitabine + efavirenz, the most widely used first-line regimens in Nicaragua, reached 14.6% and 10.4% respectively in 2015. Of note, a higher proportion of females was observed among individuals with PDR compared to individuals without PDR (OR 14.2; 95% CI: 7.1–28.4; p<0.0001). Conclusions Overall PDR in the Nicaraguan cohort was high (19.4%), with a clear increasing temporal trend in NNRTI PDR. Current HIVDR to the most frequently used first-line ART regimens in Nicaragua reached levels >10%. These observations are worrisome

  15. Feasibility of Performing Multiple Point of Care Testing for HIV Anti-Retroviral Treatment Initiation and Monitoring from Multiple or Single Fingersticks

    PubMed Central

    Gous, Natasha; Scott, Lesley; Potgieter, Joachim; Ntabeni, Lumka; Enslin, Sharon; Newman, Ronel; Stevens, Wendy

    2013-01-01

    Background Point of Care testing (POCT) provides on-site, rapid, accessible results. With current South African anti-retroviral treatment guidelines, up to 4 fingersticks /patient/clinic visit could be required if utilizing POC. We determined the feasibility and accuracy of a nurse performing multiple POCT on multiple fingersticks followed by simplification of the process by performance of multiple POC on a single fingerstick. Method and Findings Random HIV positive adult patients presenting at a HIV treatment clinic in South Africa, for ART initiation/ monitoring, were approached to participate in the study between April-June 2012. Phase I: n=150 patients approached for multiple POCT on multiple fingersticks. Phase II: n=150 patients approached for multiple POCT on a single fingerstick. The following POC tests were performed by a dedicated nurse: PIMA (CD4), HemoCue (hemoglobin), Reflotron (alanine aminotransferase, creatinine). A venepuncture specimen was taken for predicate laboratory methodology. Normal laboratory ranges and Royal College of Pathologists Australasia (RCPA) allowable differences were used as guidelines for comparison. In 67% of participants, ≥3 tests were requested per visit. All POCT were accurate but ranged in variability. Phase I: Hemoglobin was accurate (3.2%CV) while CD4, alanine aminotransferase and creatinine showed increased variability (16.3%CV; 9.3%CV; 12.9%CV respectively). PIMA generated a misclassification of 12.4%. Phase II: Hemoglobin, alanine aminotransferase and creatinine showed good accuracy (3.2%CV, 8.7%CV, 6.4%CV respectively) with increased variability on CD4 (12.4%CV) but low clinical misclassification (4.1%). No trends were observed for the sequence in which POC was performed on a single fingerstick. Overall, PIMA CD4 generated the highest error rate (16-19%). Conclusions Multiple POCT for ART initiation and/or monitoring can be performed practically by a dedicated nurse on multiple fingersticks. The process is as

  16. Self-care practices and experiences of people living with HIV not receiving antiretroviral therapy in an urban community of Lusaka, Zambia: implications for HIV treatment programmes

    PubMed Central

    2013-01-01

    Background Despite the increasingly wider availability of antiretroviral therapy (ART), some people living with HIV (PLHIV) and eligible for treatment have opted to adopt self-care practices thereby risking early AIDS-related mortality. Methods A qualitative study was conducted in urban Zambia to gain insights into PLHIV self-care practices and experiences and explore the implications for successful delivery of ART care. Between March 2010 and September 2011, in-depth interviews were conducted with PLHIV who had dropped out of treatment (n=25) and those that had opted not to initiate medication (n=37). Data was entered into and managed using Atlas ti, and analysed inductively using latent content analysis. Results PHIV used therapeutic and physical health maintenance, psychological well-being and healthy lifestyle self-care practices to maintain physical health and mitigate HIV-related symptoms. Herbal remedies, faith healing and self-prescription of antibiotics and other conventional medicines to treat HIV-related ailments were used for therapeutic and physical health maintenance purposes. Psychological well-being self-care practices used were religiosity/spirituality and positive attitudes towards HIV infection. These practices were modulated by close social network relationships with other PLHIV, family members and peers, who acted as sources of emotional, material and financial support. Cessations of sexual relationships, adoption of safe sex to avoid re-infections and uptake of nutritional supplements were the commonly used risk reduction and healthy lifestyle practices respectively. Conclusions While these self-care practices may promote physical and psychosocial well-being and mitigate AIDS-related symptoms, at least in the short term, they however undermine PLHIV access to ART care thereby putting PLHIV at risk of early AIDS-related mortality. The use of scientifically unproven herbal remedies raises health and safety concerns; faith healing may create

  17. Partner Disclosure and Early CD4 Response among HIV-Infected Adults Initiating Antiretroviral Treatment in Nairobi Kenya

    PubMed Central

    Trinh, T. Tony; Yatich, Nelly; Ngomoa, Richard; McGrath, Christine J.; Richardson, Barbra A.; Sakr, Samah R.; Langat, Agnes; John-Stewart, Grace C.; Chung, Michael H.

    2016-01-01

    Background Disclosure of HIV serostatus can have significant benefits for people living with HIV/AIDS. However, there is limited data on whether partner disclosure influences ART treatment response. Methods We conducted a retrospective cohort study of newly diagnosed, ART-naïve HIV-infected adults (>18 years) who enrolled at the Coptic Hope Center in Nairobi, Kenya between January 1st 2009 and July 1st 2011 and initiated ART within 3 months. Analysis was restricted to adults who reported to have either disclosed or not disclosed their HIV status to their partner. Analysis of CD4 response at 6 and 12 months post-ART was stratified by age group. Results Among 615 adults newly initiating ART with partner disclosure data and 12 month follow-up, mean age was 38 years and 52% were male; 76% reported that they had disclosed their HIV-status to their partner. Those who disclosed were significantly younger and more likely to be married/cohabitating than non-disclosers. At baseline, median CD4 counts were similar between disclosure groups. Among younger adults (< 38 years) those who disclosed had higher CD4 recovery than those who did not at 6 months post- ART (mean difference = 31, 95% CI 3 to 58 p = 0.03) but not at 12 months (mean difference = 17, 95% CI -19 to 52, p = 0.4). Among older adults (≥ 38years) there was no observed difference in CD4 recovery at 6 or 12 months between disclosure groups. Conclusion Among younger adults, disclosure of HIV status to partners may be associated with CD4 recovery following ART. PMID:27711164

  18. Living with HIV, antiretroviral treatment experience and tobacco smoking: results from a multisite cross-sectional study

    PubMed Central

    Duval, Xavier; Baron, Gabriel; Garelik, Daniel; Villes, Virginie; Dupré, Thierry; Leport, Catherine; Lert, France; Peretti-Watel, Patrick; Ravaud, Philippe; Spire, Bruno

    2008-01-01

    Objective To assess prevalence of, and factors associated with tobacco smoking and dependence in HIV patients. Design A one-day cross-sectional national survey. Methods 727 consecutive outpatients from a representative sample of 82 French units specialized in HIV-infected patient care were asked to complete a self-administered questionnaire, assessing smoking habits, dependence, cessation motivation, other substance abuse, socio-cultural characteristics, life with HIV and its treatment. Smoking prevalence and dependence were assessed and compared with a representative sample of the general French population; associated factors were determined. Results 593 (82%) patients completed the questionnaire, 12% were active or ex-intravenous drug users, 37% were homosexual men; 43% were active smokers (31% in the French population). Fifty-six percent of smokers were classified as moderately or highly dependent, 14% of smokers were highly motivated and free of other substance abuse and of depressive symptoms. Smoking was independently associated with male sex (OR=2.38; 95% CI: 0.99–1.11), BMI (OR=1.08; 95% CI: 1.14-1.03), smoking environment (OR=4.75; 95% CI: 3.02–7.49), excessive alcohol consumption (OR=2.50; 95% CI: 1.20–5.23), illicit drug use (OR=2.43; 95% CI: 1.41–4.19), HIV status disclosure to family (OR=1.81; 95% CI: 1.16–2.85) and experience of rejection due to disclosure (OR=1.90; 95% CI: 1.14–3.17). Disclosure and drug substitutes’ usage were associated with high tobacco dependence. Conclusions Tobacco smoking is frequent and associated with other substance use and HIV disclosure. The rate of smokers who would be good candidates for a standard tobacco cessation program appears very low. Tobacco reduction or cessation strategies should be adapted to this population. PMID:18572752

  19. Combinations of Drugs in the Treatment of Obesity

    PubMed Central

    Halpern, Bruno; Oliveira, Eduardo S. L.; Faria, André M.; Halpern, Alfredo; de Melo, Maria Edna; Cercato, Cintia; Mancini, Marcio C.

    2010-01-01

    Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.

  20. Current Perspectives on HIV-1 Antiretroviral Drug Resistance

    PubMed Central

    Iyidogan, Pinar; Anderson, Karen S.

    2014-01-01

    Current advancements in antiretroviral therapy (ART) have turned HIV-1 infection into a chronic and manageable disease. However, treatment is only effective until HIV-1 develops resistance against the administered drugs. The most recent antiretroviral drugs have become superior at delaying the evolution of acquired drug resistance. In this review, the viral fitness and its correlation to HIV-1 mutation rates and drug resistance are discussed while emphasizing the concept of lethal mutagenesis as an alternative therapy. The development of resistance to the different classes of approved drugs and the importance of monitoring antiretroviral drug resistance are also summarized briefly. PMID:25341668

  1. First-line antiretroviral therapy durability in a 10-year cohort of naïve adults started on treatment in Uganda

    PubMed Central

    Castelnuovo, Barbara; Kiragga, Agnes; Mubiru, Frank; Kambugu, Andrew; Kamya, Moses; Reynolds, Steven J

    2016-01-01

    Introduction The majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes. Methods At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence. Results Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment

  2. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment

    PubMed Central

    Baroncelli, Silvia; Pirillo, Maria F.; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Antoni, Anna Degli; Galluzzo, Clementina M.; Stentarelli, Chiara; Amici, Roberta

    2015-01-01

    Abstract There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but <37 copies/ml), and quantifiable HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA <37 copies/ml. Most of them (59/90, 65.6%) had full suppression, with the remaining (31/90, 34.4%) showing low-level viremia (median: 11.9 copies/ml; IQR 7.4–16.3). Among the 17 women with quantifiable viral load, median HIV-RNA was 109 copies/ml (IQR 46–251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and

  3. Patching the gaps towards the 90–90–90 targets: outcomes of Nigerian children receiving antiretroviral treatment who are co-infected with tuberculosis

    PubMed Central

    Chamla, Dick D; Asadu, Chukwuemeka; Davies, Abiola; de Wagt, Arjan; Ilesanmi, Oluwafunke; Adeyinka, Daniel; Adejuyigbe, Ebun

    2015-01-01

    Introduction Nigeria has a high burden of children living with HIV and tuberculosis (TB). This article examines the magnitude of TB among children receiving antiretroviral treatment (ART), compares their ART outcomes with their non-TB counterparts and argues that addressing TB among children on ART is critical for achieving the 90–90–90 targets. Methods This was a facility-based, retrospective analysis of medical records of children aged <15 years who were newly initiated on ART between 2011 and 2012. Structured tools were used to collect data. STATA software was used to perform descriptive, survival and multivariate analyses. Results A total of 1142 children with a median age of 3.5 years from 20 selected facilities were followed for 24 months. Of these, 95.8% were assessed for TB at ART initiation and 14.7% had TB. Children on ART were more likely to have TB if they were aged 5 years or older (p<0.01) and had delayed ART initiation (p<0.05). The cotrimoxazole and isoniazid prophylaxes were provided to 87.9 and 0.8% of children, respectively. The rate of new TB cases was 3 (2.2–4.0) per 100 person-years at six months and declined to 0.2 (0.06–1.4) per 100 person-years at 24 months. TB infection [adjusted hazard ratio (aHR): 4.3; 2.3–7.9], malnutrition (aHR: 5.1; 2.6–9.8), delayed ART initiation (aHR: 3.2; 1.5–6.7) and age less than 1 year at ART initiation (aHR: 4.0; 1.4–12.0) were associated with death. Additionally, patients with TB (aHR: 1.3; 1.1–1.6) and children below the age of 1 at ART initiation (aHR: 2.9; 1.7–5.2) were more likely to be lost to follow-up (LFU). Conclusions Children on ART with TB are less likely to survive and more likely to be LFU. These risks, along with low isoniazid uptake and delayed ART initiation, present a serious challenge to achieving the 90–90–90 targets and underscore an urgent need for inclusion of childhood TB/HIV in global plans and reporting mechanisms. PMID:26639112

  4. Survival on antiretroviral treatment among adult HIV-infected patients in Nepal: a retrospective cohort study in far-western Region, 2006–2011

    PubMed Central

    2013-01-01

    Background Though financial and policy level efforts are made to expand antiretroviral treatment (ART) service free of cost, survival outcome of ART program has not been systematically evaluated in Nepal. This study assesses the mortality rates and determinants among adult HIV-infected patients on ART in Far-western region of Nepal. Methods This retrospective cohort study included 1024 (51.2% men) HIV-infected patients aged ≥15 years, who started ART between May 15th 2006 and May 15th 2011 in five ART sites in the Far-western region, Nepal. Follow-up time was calculated from the date of ART initiation to date of death or censoring (loss to follow-up, transferred out, or 15 November 2011). Mortality rates (per 100 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore determinants of mortality. Results The median follow-up time was 19.1 months. The crude mortality rate was 6.3 (95% confidence interval (CI) 5.3-7.6) but more than three-times higher in first 3 months after ART initiation (21.9 (95% CI 16.6- 28.8)). About 12% (83% men) of those newly initiated on ART died during follow-up. The independent determinants of mortality were male sex (hazard ratio (HR) 4.55, 95% CI 2.43-8.51), poor baseline performance scale (bedridden <50% of the day during the past month, HR 2.05, 95% CI 1.19-3.52; bedridden >50% of the day during the past month, HR 3.41, 95% CI 1.67-6.98 compared to normal activity), one standard deviation decrease in baseline bodyweight (HR 1.04, 95% CI 1.01-1.07), and poor WHO clinical stage (stage III, HR 2.96, 95% CI 1.31-6.69; stage IV, HR 3.28, 95% CI 1.30-8.29 compared to WHO clinical stage I or II). Conclusions High mortality was observed within the first 3 months of ART initiation. Patients with poor baseline clinical characteristics had higher mortality, especially men. Earlier initiation of ART through expanded testing and counselling should be encouraged in HIV-infected patients. PMID

  5. Effect of combined treatments on viscosity of whey dispersions

    NASA Astrophysics Data System (ADS)

    Camillo, A.; Sabato, S. F.

    2004-09-01

    Whey proteins, enriched protein fractions from milk, are of great interest as ingredients due to nutritional value associated with its functional properties. These proteins could have their structural properties improved when some treatments are applied, such as thermal and gamma irradiation or when some compounds are added. The current work aimed to study the viscometer behavior of whey dispersions submitted to two different combined treatments: (1) thermal plus irradiation and (2) thermal plus vacuum and N 2 plus irradiation. Dispersions of whey protein in water (5% and 8% protein (w/v) base) and containing proteins and glycerol at ratios 1:1 and 2:1 (protein:glycerol) were submitted to both combined treatments. The irradiation doses were 0, 5, 15 and 25 kGy. The viscosity of the two combined treatments and for four levels of absorbed doses is presented and the combined effects are discussed. The thermal treatment combined with gamma irradiation contributed to increase the viscosity as irradiation doses increases for both (5% and 8%) concentrations of proteins ( p<0.05). For protein and glycerol solutions, the irradiation dose seemed to result in a slightly increase. The vacuum applied before the irradiation showed a small contribution.

  6. Combination anticonvulsant treatment of soman-induced seizures.

    PubMed

    Koplovitz, I; Schulz, S; Shutz, M; Railer, R; Macalalag, R; Schons, M; McDonough, J

    2001-12-01

    These studies investigated the effectiveness of combination treatment with a benzodiazepine and an anticholinergic drug against soman-induced seizures. The anticholinergic drugs considered were biperiden, scopolamine, trihexaphenidyl, and procyclidine; the benzodiazepines were diazepam and midazolam. Male guinea pigs were implanted surgically with cortical screw electrodes. Electrocorticograms were displayed continually and recorded on a computerized electroencephalographic system. Pyridostigmine (0.026 mg x kg(-1), i.m.) was injected as a pretreatment to inhibit red blood cell acetylcholinesterase by 30-40%. Thirty minutes after pyridostigmine, 2 x LD50 (56 microg x kg(-1)) of soman was injected s.c., followed 1 min later by i.m. treatment with atropine (2 mg x kg(-1)) + 2-PAM (25 mg x kg(-1)). Electrographic seizures occurred in all animals. Anticonvulsant treatment combinations were administered i.m. at 5 or 40 min after seizure onset. Treatment consisted of diazepam or midazolam plus one of the above-mentioned anticholinergic drugs. All doses of the treatment compounds exhibited little or no antiseizure efficacy when given individually. The combination of a benzodiazepine and an anticholinergic drug was effective in terminating soman-induced seizure, whether given 5 or 40 min after seizure onset. The results suggest a strong synergistic effect of combining benzodiazepines with centrally active anticholinergic drugs and support the concept of using an adjunct to supplement diazepam for the treatment of nerve-agent-induced seizures.

  7. Propranolol, doxycycline and combination therapy for the treatment of rosacea.

    PubMed

    Park, Jung-Min; Mun, Je-Ho; Song, Margaret; Kim, Hoon-Soo; Kim, Byung-Soo; Kim, Moon-Bum; Ko, Hyun-Chang

    2015-01-01

    Doxycycline is the standard systemic treatment for rosacea. Recently, there have been a few reports on β-adrenergic blockers such as nadolol, carvedilol and propranolol for suppressing flushing reactions in rosacea. To our knowledge, there are no comparative studies of propranolol and doxycycline, and combination therapy using both. The aim of this study was to investigate and compare the efficacy and safety of monotherapy of propranolol, doxycycline and combination therapy. A total of 78 patients who visited Pusan National University Hospital and were diagnosed with rosacea were included in this study. Among them, 28 patients were in the propranolol group, 22 the doxycycline group and 28 the combination group. We investigated the patient global assessment (PGA), investigator global assessment (IGA), assessment of rosacea clinical score (ARCS) and adverse effects. Improvement in PGA and IGA scores from baseline was noted in all groups, and the combination therapy was found to be the most effective during the entire period, but this was statistically insignificant. The reduction rate of ARCS during the treatment period was also highest in the combination group (57.4%), followed by the doxycycline group (52.2%) and the propranolol group (51.0%). Three patients in the combination group had mild and transient gastrointestinal disturbances but there was no significant difference from the other groups. We conclude that the combination therapy of doxycycline and propranolol is effective and safe treatment for rosacea and successful for reducing both flushing and papulation in particular.

  8. Photodynamic Therapy and Its Role in Combined Modality Anticancer Treatment.

    PubMed

    Brodin, N Patrik; Guha, Chandan; Tomé, Wolfgang A

    2015-08-01

    Photodynamic therapy (PDT) is a relatively new modality for anticancer treatment and although the interest has increased greatly in the recent years, it is still far from clinical routine. As PDT consists of administering a nontoxic photosensitizing chemical and subsequently illuminating the tumor with visible light, the treatment is not subject to dose-limiting toxicity, which is the case for established anticancer treatments like radiation therapy or chemotherapy. This makes PDT an attractive adjuvant therapy in a combined modality treatment regimen, as PDT provides an antitumor immune response through its ability to elicit the release of damage-associated molecular patterns and tumor antigens, thus providing an increased antitumor efficacy, potentially without increasing the risk of treatment-related toxicity. There is great interest in the elicited immune response after PDT and the potential of combining PDT with other forms of treatment to provide potent antitumor vaccines. This review summarizes recent studies investigating PDT as part of combined modality treatment, hopefully providing an accessible overview of the current knowledge that may act as a basis for new ideas or systematic evaluations of already promising results.

  9. A single centre cohort experience with a new once daily antiretroviral drug

    PubMed Central

    Stebbing, J; Bower, M; Holmes, P; Gazzard, B; Nelson, M

    2006-01-01

    Background Atazanavir, an azadipeptide protease inhibitor (PI) with once daily dosing, a lack of insulin resistance, lipid increase, and gastrointestinal toxicities, is approved in combination with other antiretrovirals for the treatment of patients infected with HIV. Unboosted atazanavir is also used in highly active antiretroviral therapy (HAART) naive patients. Methods The study prospectively followed up an established cohort of patients who received atazanavir, and for whom one year of follow up data were available. Results It was found that use of atazanavir in intent to treat and on treatment analyses, maintained and led to virological suppression and increases in CD4 count in both PI naive and experienced patients. Virological failure occurred in 7% of patients and the main toxicity was hyperbilirubinaemia, which led to treatment withdrawal in 2%. Its efficacy and safety profile was similar to that seen in previous randomised studies investigating its use. Conclusions These data should provide reassurance for clinicians wishing to introduce a new antiretroviral into an established cohort. PMID:16679474

  10. Combination treatment with interferon and ribavirin for chronic hepatitis C.

    PubMed

    Davis, G L

    1999-11-01

    Interferon was the first drug shown to be effective in patients with chronic hepatitis C, but initial treatment regimens achieved sustained loss of virus in only a small minority of patients. The combination of IFN with ribavirin now makes sustained response rates of 30% to 40% possible. This is quite a remarkable achievement for a pharmacologic treatment of a chronic viral infection. It is now reasonable to assume that early treatment and eradication of chronic hepatitis C might reduce the growing burden of hepatitis C and its complications on the healthcare system. Future researchers will strive to optimize combination treatment regimens. Longer treatment courses and intensified induction regimens using either daily dosing, high doses, or both may improve long-term response, but this remains speculative. Other forms of IFN may improve response or increase the ease of drug administration. Conjugation of biologic compounds to polyethylene glycol can result in significant prolongation of plasma half-life while maintaining the properties of the parent molecule. Some biologic properties may be altered, however, so pegylated IFN must continue to be evaluated in clinical trials. There is limited clinical data on other recombinant or natural interferons in combination with oral ribavirin, however, these may prove to be equally effective. Combinations of IFN with one or more other antiviral, anti-inflammatory, or immune modulatory agents will need to be studied. Although amantidine is not effective against hepatitis C as a single agent or in combination with IFN, the combination of IFN, ribavirin, and rimantidine has been shown to have antiviral activity superior to the IFN-ribavirin combination against influenza virus and possibly against HCV. PMID:11291252

  11. [FEATURES OF DIAGNOSTICS AND TREATMENT OF EXTREMELY SEVERE COMBINED INJURY].

    PubMed

    Tulupov, A N; Besaev, G M; Sinenchenko, G I; Taniya, S Sh; Bagdasar'yants, V G

    2015-01-01

    The data of examination and treatment of 356 victims with extremely severe combined injury and shock of III degree were analyzed. All the patients had a medical unfavorable life prognosis. On the basis of the research, it was proved, that the modern approach of treatment of such trauma should include an adequate anti-shock treatment in conditions of the first-level trauma center. The operative activity should be increased in cases of combined trauma of bones by their early external fixation. The authors recommend an application of up-to-date prevention sepsis treatment, late reconstructive--restorative operation performance after its full relief and nutritive metabolic therapy. This approach allowed reducing of the rate of life-threaten infectious complications on 32.4% and noninfectious--on 31.7%, the lethality--on 24%. PMID:27066655

  12. Nanoparticle-Based Combination Therapy for Cancer Treatment.

    PubMed

    Yhee, Ji Young; Son, Sejin; Lee, Hyukjin; Kim, Kwangmeyung

    2015-01-01

    In recent years, combination of different types of therapies using nanoparticles has emerged as an advanced strategy for cancer treatment. Most of all, combination of chemotherapeutic drug and siRNA in nanoformulation has shown a great potential, because siRNA-mediated specific gene silencing can compensate for the incomplete anti-cancer actions of chemotherapy. In this article, nanoparticle-based combination therapy for cancer treatment is introduced to be focused on the therapeutic chemical and siRNA combination. It is classified into 3 groups: 1) general chemotherapy combined with siRNA carrying nanoparticle, 2) co-delivery of chemical and siRNA therapeutics within a single nanoparticle, and 3) Use of multiple nanoparticles for chemical and siRNA therapeutics. The purpose of the combination and the mechanisms of anti-cancer action was described according to the categories. Examples of some recent developments of nanotechnology-based chemo- and siRNA- therapeutics combination therapy are summarized for better understanding of its practical application.

  13. Pulmonary function in an international sample of HIV-positive, treatment-naïve adults with CD4 counts >500 cells/μL: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    KUNISAKI, Ken M.; NIEWOEHNER, Dennis E.; COLLINS, Gary; NIXON, Daniel E.; TEDALDI, Ellen; AKOLO, Christopher; KITYO, Cissy; KLINKER, Hartwig; LA ROSA, Alberto; CONNETT, John E.

    2014-01-01

    Objectives To describe the prevalence and correlates of chronic obstructive pulmonary disease (COPD) in a multicentre international cohort of persons living with HIV (PLWH). Methods We performed a cross-sectional analysis of adult PLWH, naïve to HIV treatment, with baseline CD4 cell count >500 cells/μL enrolled in the Pulmonary Substudy of the Strategic Timing of AntiRetroviral Treatment trial. We collected standardised, quality-controlled spirometry. COPD was defined as forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio less than the lower limit of normal. Results Among 1026 participants from 80 sites and 20 countries, median (IQR) age was 36 (30, 44) years, 29% were female, and time since HIV diagnosis was 1.2 (0.4, 3.5) years. Baseline CD4 cell count was 648 (583, 767) cells/μL, viral load was 4.2 (3.5, 4.7) log10 copies/mL, and 10% had viral load ≤400 copies/mL despite lack of HIV treatment. Current/former/never smokers comprised 28%/11%/61% of the cohort, respectively. COPD was present in 6.8% of participants, and varied by age, smoking status, and region. 48% of those with COPD reported lifelong nonsmoking. In multivariable regression, age and pack-years of smoking had the strongest associations with FEV1/FVC ratio (p<0.0001). There were significant differences between the effect of region on FEV1/FVC ratio (p=0.010). Conclusions Our data suggest that among PLWH, naïve to HIV treatment and with CD4 cell count >500 cells/μL, smoking and age are important factors related to COPD. Smoking cessation should remain a high global priority for clinical care and research in PLWH. PMID:25711330

  14. Combined Psychotherapy/Medication Treatment: The Valpo Model

    ERIC Educational Resources Information Center

    Cooper, Stewart E.

    2007-01-01

    This article presents how the Valparaiso University Student Counseling and Development Center (SCDC) developed and delivers a combined service treatment model integrating pharmacotherapy with psychotherapy for a subset of the center's clients evidencing significant psychiatric concerns. To explicate the model, several documents that may be of…

  15. Nanoparticle Based Combination Treatments for Targeting Multiple Hallmarks of Cancer

    PubMed Central

    VanDyke, D; Kyriacopulos, P; Yassini, B; Wright, A; Burkhart, E; Jacek, S; Pratt, M; Peterson, CR; Rai, P

    2016-01-01

    Treatment of cancer remains one of the most challenging tasks facing the healthcare system. Cancer affects the lives of millions of people and is often fatal. Current treatment methods include surgery, chemotherapy, radiation therapies or some combinations of these. However, recurrence is a major problem. These treatments can be invasive with severe side effects. Inefficacies in treatments are a result of the complex and variable biology of cancerous cells. Malignant tumor cells and normal functioning cells share many of the same biological characteristics but the main difference is that in cancer cells there is in an overuse and over expression of these biological characteristics. These pertinent characteristics can be grouped into eight hallmarks, as illustrated by Hanahan and Weinberg. These characteristics include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. In order to provide a noninvasive, effective treatment, delivery methods must be explored in order to transport cytotoxic agents used for targeting the hallmarks of cancer in a safer and more effective fashion. The use of nanoparticles as drug delivery carriers provides an effective method in which multiple cytotoxic agents can be safely delivered to cancer tissue to simultaneously target multiple hallmarks. By targeting multiple hallmarks of cancer at once, the efficacy of cancer treatments could be improved drastically. This review explores the uses and efficacy of combination therapies using nanoparticles that can simultaneously target multiple hallmarks of cancer. PMID:27547592

  16. Combined bacterial and viral treatment: a novel anticancer strategy

    PubMed Central

    2015-01-01

    An idea for a new combination therapy will be described herein. It is a proposition to combine viral and bacterial anticancer therapies and make them fight cancer in concert. We analyzed biological anticancer therapies and found overlapping advantages and disadvantages which led us to the conclusion that the combination therapy has the potential to create a new therapeutic quality. It is surprising how many weaknesses of viral anticancer therapy are the strengths of bacterial anticancer therapies and the other way round. We review the facts behind this concept and try to assess its value. We propose a few strategies how to combine these two therapies but as far as the review can go, final answers will have to come from the experiments. This review is the first attempt to describe a new strategy and understand the means for this idea but also to raise new questions and discuss new ways to look at anti-cancer treatment. PMID:26648783

  17. Individualization of antiretroviral therapy - Pharmacogenomic aspect

    PubMed Central

    Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K.

    2015-01-01

    Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID:26831415

  18. Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

    2013-10-01

    The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.

  19. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    PubMed

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. PMID:27089522

  20. Combined treatment of Pseudomonas aeruginosa biofilms with bacteriophages and chlorine.

    PubMed

    Zhang, Yanyan; Hu, Zhiqiang

    2013-01-01

    Bacterial biofilms are a growing concern in a broad range of areas. In this study, a mixture of RNA bacteriophages isolated from municipal wastewater was used to control and remove biofilms. At the concentrations of 400 and 4 × 10(7) PFU/mL, the phages inhibited Pseudomonas aeruginosa biofilm formation by 45 ± 15% and 73 ± 8%, respectively. At the concentrations of 6,000 and 6 × 10(7) PFU/mL, the phages removed 45 ± 9% and 75 ± 5% of pre-existing P. aeruginosa biofilms, respectively. Chlorine reduced biofilm growth by 86 ± 3% at the concentration of 210 mg/L, but it did not remove pre-existing biofilms. However, a combination of phages (3 × 10(7) PFU/mL) and chlorine at this concentration reduced biofilm growth by 94 ± 2% and removed 88 ± 6% of existing biofilms. In a continuous flow system with continued biofilm growth, a combination of phages (a one-time treatment at the concentration of 1.9 × 10(8) PFU/mL for 1 h first) with chlorine removed 97 ± 1% of biofilms after Day 5 while phage and chlorine treatment alone removed 89 ± 1% and 40 ± 5%, respectively. For existing biofilms, a combined use of a lower phage concentration (3.8 × 10(5) PFU/mL) and chlorination with a shorter time duration (12 h) followed by continuous water flushing removed 96 ± 1% of biofilms in less than 2 days. Laser scanning confocal microscopy supplemented with electron microscopy indicated that the combination treatment resulted in biofilms with lowest cell density and viability. These results suggest that the combination treatment of phages and chlorine is a promising method to control and remove bacterial biofilms from various surfaces.

  1. Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina.

    PubMed

    Fiscus, S A; Adimora, A A; Schoenbach, V J; McKinney, R; Lim, W; Rupar, D; Kenny, J; Woods, C; Wilfert, C; Johnson, V A

    1999-07-01

    Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997. Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997. The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005). None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine.

  2. Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

    PubMed

    Gatell, J M

    1998-01-01

    In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a

  3. [The combined treatment of osteogenesis imperfecta in children].

    PubMed

    Berezhnoĭ, A P; Shilov, A V; Belova, N A; Snetkov, A I

    1989-12-01

    The authors present the results of complex drug and orthopaedic treatment of children with imperfect osteogenesis. 40 patients were treated with a somatotropic hormone, calcitrin and vitamin D metabolites (oxydevit and dihydrocholecalciferol). In 20 of these patients corrective osteotomies of the long bones of the lower extremities combined with metal osteosynthesis with rods and massive plates were performed. In a number of patients osteoplasty with long cortical allografts was made. After the treatment all the children were able to move independently either with the aid of unloading orthopaedic apparatuses (17 patients), or without them (3 patients). PMID:2628828

  4. HIV-1 antiretroviral drug therapy.

    PubMed

    Arts, Eric J; Hazuda, Daria J

    2012-04-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with specific pharmacological agents. To date, an arsenal of 24 Food and Drug Administration (FDA)-approved drugs are available for treatment of HIV-1 infections. These drugs are distributed into six distinct classes based on their molecular mechanism and resistance profiles: (1) nucleoside-analog reverse transcriptase inhibitors (NNRTIs), (2) non-nucleoside reverse transcriptase inhibitors (NNRTIs), (3) integrase inhibitors, (4) protease inhibitors (PIs), (5) fusion inhibitors, and (6) coreceptor antagonists. In this article, we will review the basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure (i.e., drug resistance).

  5. Combined Treatment Of Purulent Wounds With CO2 Laser

    NASA Astrophysics Data System (ADS)

    Tolstych, P. I.; Skobelkin, O. K.; Derbenev, V. A.

    1988-06-01

    The authors have worked out a programme for combined treatment of purulent wounds with CO2 laser. It consists of following components: a) laserinsision of suppurative wounds,necrectomy,or irradiation of the incised wound with the defocused laser beam; b )diplication of proteinerses and antiseptics immobilized on the textile dressing and dranaige materials; c) applications of biocompatible materials with the immobilized antiseptics and enzyme agents; d) application of low energy laser irradiation in the postoperative period; e) lavage of the sutured wound if indicated. The points of the above-mentioned programme can be used separately as independed methods in several thousands of patients. Their combined applications has been studied on 400 patients. Such treatment allowed to refuse the antibioticotherapy in 98,3% of cases,to reduce the terms of trestment in I,5-2 % times as compared with traditional methods, and to low significantely costs.

  6. Surgical treatment combined with NSAIDs in fibrodysplasia ossificans progressiva.

    PubMed

    Seok, Yangki; Cho, Sukki; Lee, Eungbae

    2012-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic ossification. There is no effective treatment. Conservative management is unsuccessful, and operation result in failure because new ectopic bone forms at the operative site. We report a 10-year-old boy with FOP who underwent surgical management combined with non-steroidal anti-inflammatory drugs (NSAIDs).

  7. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

    PubMed Central

    Garcia, Hector H; Lescano, Andres G; Lanchote, Vera L; Pretell, E Javier; Gonzales, Isidro; Bustos, Javier A; Takayanagui, Osvaldo M; Bonato, Pierina S; Horton, John; Saavedra, Herbert; Gonzalez, Armando E; Gilman, Robert H

    2011-01-01

    AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. PMID:21332573

  8. Combined chemical treatment of pharmaceutical effluents from medical ointment production.

    PubMed

    Kulik, Niina; Trapido, Marina; Goi, Anna; Veressinina, Yelena; Munter, Rein

    2008-02-01

    Three wastewater samples from a pharmaceutical plant formulating medical ointments were subjected to lab-scale treatment by a Fenton-like system in combination with lime coagulation. All samples were plant pre-treated by adsorption/flocculation/filtration processes with utilization of bentonite, but the quality of effluents did not comply with the regulations for wastewater discharged to local sewerage. The optimization of Fenton-like oxidation demonstrated the highest process efficacy at H(2)O(2)/COD weight ratio of 2:1, H(2)O(2)/Fe(2+) molar ratio of 10:1 and 2h of treatment time. The fast pH decrease to acidic values approximately 3 during first min of oxidation for all effluents suggested that pH adjustment was unnecessary. Combination of Fe(III) precipitation and lime coagulation proved feasible to improve considerably COD and residual iron concentration reduction in pharmaceutical effluents. Additionally, considerable BOD(7) reduction and BOD(7)/COD ratio improvement of pharmaceutical wastewater samples was achieved by combined treatment. The application of Fenton-like oxidation with subsequent iron (III)/lime coagulation did not only enhance the quality of pharmaceutical effluents with different chemical characteristics and help to meet the requirements for wastewater discharged to sewage, but also improve the biodegradability of pharmaceutical effluents.

  9. Combined chemical treatment of pharmaceutical effluents from medical ointment production.

    PubMed

    Kulik, Niina; Trapido, Marina; Goi, Anna; Veressinina, Yelena; Munter, Rein

    2008-02-01

    Three wastewater samples from a pharmaceutical plant formulating medical ointments were subjected to lab-scale treatment by a Fenton-like system in combination with lime coagulation. All samples were plant pre-treated by adsorption/flocculation/filtration processes with utilization of bentonite, but the quality of effluents did not comply with the regulations for wastewater discharged to local sewerage. The optimization of Fenton-like oxidation demonstrated the highest process efficacy at H(2)O(2)/COD weight ratio of 2:1, H(2)O(2)/Fe(2+) molar ratio of 10:1 and 2h of treatment time. The fast pH decrease to acidic values approximately 3 during first min of oxidation for all effluents suggested that pH adjustment was unnecessary. Combination of Fe(III) precipitation and lime coagulation proved feasible to improve considerably COD and residual iron concentration reduction in pharmaceutical effluents. Additionally, considerable BOD(7) reduction and BOD(7)/COD ratio improvement of pharmaceutical wastewater samples was achieved by combined treatment. The application of Fenton-like oxidation with subsequent iron (III)/lime coagulation did not only enhance the quality of pharmaceutical effluents with different chemical characteristics and help to meet the requirements for wastewater discharged to sewage, but also improve the biodegradability of pharmaceutical effluents. PMID:17897701

  10. The Cost of Providing Combined Prevention and Treatment Services, Including ART, to Female Sex Workers in Burkina Faso

    PubMed Central

    Cianci, Fiona; Sweeney, Sedona; Konate, Issouf; Nagot, Nicolas; Low, Andrea; Mayaud, Philippe; Vickerman, Peter

    2014-01-01

    Background Female Sex workers (FSW) are important in driving HIV transmission in West Africa. The Yerelon clinic in Burkina Faso has provided combined preventative and therapeutic services, including anti-retroviral therapy (ART), for FSWs since 1998, with evidence suggesting it has decreased HIV prevalence and incidence in this group. No data exists on the costs of such a combined prevention and treatment intervention for FSW. This study aims to determine the mean cost of service provision per patient year for FSWs attending the Yerelon clinic, and identifies differences in costs between patient groups. Methods Field-based retrospective cost analyses were undertaken using top-down and bottom-up costing approaches for 2010. Expenditure and service utilisation data was collated from primary sources. Patients were divided into groups according to full-time or occasional sex-work, HIV status and ART duration. Patient specific service use data was extracted. Costs were converted to 2012 US$. Sensitivity analyses considered removal of all research costs, different discount rates and use of different ART treatment regimens and follow-up schedules. Results Using the top-down costing approach, the mean annual cost of service provision for FSWs on or off ART was US$1098 and US$882, respectively. The cost for FSWs on ART reduced by 29%, to US$781, if all research-related costs were removed and national ART monitoring guidelines were followed. The bottom-up patient-level costing showed the cost of the service varied greatly across patient groups (US$505–US$1117), primarily due to large differences in the costs of different ART regimens. HIV-negative women had the lowest annual cost at US$505. Conclusion Whilst FSWs may require specialised services to optimise their care and hence, the public health benefits, our study shows that the cost of ART provision within a combined prevention and treatment intervention setting is comparable to providing ART to other population groups

  11. Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV-specific CD4⁺ T-cell-dependent natural killer cell effector responses in chronically infected rhesus macaques.

    PubMed

    Vargas-Inchaustegui, Diego A; Xiao, Peng; Demberg, Thorsten; Pal, Ranajit; Robert-Guroff, Marjorie

    2015-06-01

    Natural killer (NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. We have previously shown that interleukin-2-dependent NK and CD4(+) T-cell co-operative immune responses exist in long-term simian immunodeficiency virus (SIV) -infected controlling macaques and can be rescued in SIV-infected non-controlling macaques by a short course of antiretroviral therapy (ART). Given that co-operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV-infected macaques by vaccination with a single-dose of envelope protein given during ART. To this end, we treated 14 chronically SIV-infected macaques with ART for 11 weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4(+) T cells in all macaques, and increased T-cell-dependent envelope- and gag-specific interferon-γ and tumour necrosis factor-α production by circulatory CD56(+) NK cells. The therapeutic envelope immunization resulted in higher envelope-specific responses compared with those in macaques that received ART only. Functional T-cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV-specific T-cell-dependent NK cell responses can be efficiently rescued by ART in chronically SIV-infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals.

  12. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia

    PubMed Central

    Cipriani, Andrea; Boso, Marianna; Barbui, Corrado

    2014-01-01

    Background Although clozapine has been shown to be the treatment of choice in people with schizophrenia that are resistant to treatment, one third to two thirds of people still have persistent positive symptoms despite clozapine monotherapy of adequate dosage and duration. The need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine is the most common reason for simultaneously prescribing a second antipsychotic drug in combination with clozapine. Objectives To determine the efficacy and tolerability of various clozapine combination strategies with antipsychotics in people with treatment resistant schizophrenia. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2008) and MEDLINE (up to November 2008). We checked reference lists of all identified randomised controlled trials and requested pharmaceutical companies marketing investigational products to provide relevant published and unpublished data. Selection criteria We included only randomised controlled trials recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug. Data collection and analysis Two review authors independently extracted data and resolved disagreement by discussion with third member of the team. When insufficient data were provided, we contacted the study authors. Main results Three small (range of number of participants 28 to 60) randomised controlled trials were included in the review. Even though results from individual studies did not find that one combination strategy is better than the others, the methodological quality of included studies was too low to allow authors to use the collected data to answer the research question correctly. Authors’ conclusions In this review we considered the risk of bias too high because of

  13. Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals.

    PubMed

    Perram, Jacinta; Joseph, Joanne; Holloway, Cameron

    2015-01-01

    Compatibility of novel oral anticoagulants in patients with HIV taking combined antiretroviral therapy has not been established, with no published reports of successful concurrent use. We present a case where chronic anticoagulation was indicated in a patient with treated HIV and non-valvular atrial fibrillation who refused warfarin therapy. The patient tolerated the combination, with dabigatran blood levels within the expected range at a standard dosing regimen, without evidence of bleeding or other adverse outcomes. While further research is needed to establish the role of novel oral anticoagulants in patients taking antiretrovirals, this case suggests that dabigatran may be a viable option for selected patients.

  14. HIV reverse transcriptase gene mutations in anti-retroviral treatment naïve rural people living with HIV/AIDS.

    PubMed

    Mohanakrishnan, K; Kasthuri, A; Amsavathani, S K; Sumathi, G

    2015-01-01

    This study is designed to find out the mutational variations of reverse transcriptase (RT) gene of HIV, after the traditional drug usage among anti-retroviral therapy naïve rural people living with HIV/AIDS. HIV Reactive patients, who were exposed for indigenous medicines such as Siddha, Ayurveda etc., for a minimum period of 6 months were taken for this study. Among 40 patients, two samples (5.55%) demonstrated high-level mutational resistance variations for nucleoside RT inhibitor (NRTI) and non-NRTI. The predominant polymorphisms detected were K122E (91.7%), V60I (91.7%), V35T (89%), Q207E (89%), D177E (89%), T200A (86.1%), S48T (83.33%), K173A (80.6%).

  15. HIV reverse transcriptase gene mutations in anti-retroviral treatment naïve rural people living with HIV/AIDS.

    PubMed

    Mohanakrishnan, K; Kasthuri, A; Amsavathani, S K; Sumathi, G

    2015-01-01

    This study is designed to find out the mutational variations of reverse transcriptase (RT) gene of HIV, after the traditional drug usage among anti-retroviral therapy naïve rural people living with HIV/AIDS. HIV Reactive patients, who were exposed for indigenous medicines such as Siddha, Ayurveda etc., for a minimum period of 6 months were taken for this study. Among 40 patients, two samples (5.55%) demonstrated high-level mutational resistance variations for nucleoside RT inhibitor (NRTI) and non-NRTI. The predominant polymorphisms detected were K122E (91.7%), V60I (91.7%), V35T (89%), Q207E (89%), D177E (89%), T200A (86.1%), S48T (83.33%), K173A (80.6%). PMID:26470965

  16. Strategies for Living with the Challenges of HIV and Antiretroviral Use in Zambia

    ERIC Educational Resources Information Center

    Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.

    2009-01-01

    This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…

  17. 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

  18. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  19. Approaches to interferon combination therapy in the treatment of AIDS.

    PubMed

    Krown, S E

    1990-02-01

    High-dose interferon alfa (IFN alfa) therapy induces an overall response rate of 25% to 30% in unselected patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Up to 50% of patients with relatively preserved immune reactivity respond to treatment. However, when dosages of 20 x 10(6) units or more per day are used to induce responses, constitutional and hematologic side effects may be significant. Therefore, efforts are being made to lower the effective dose of IFN alfa. One effort involves combining IFN alfa with zidovudine (AZT; Retrovir; Burroughs Wellcome, Research Triangle Park, NC). These agents act synergistically to block the multiplication of human immunodeficiency virus (HIV) in vitro. The drugs act at different points in the HIV multiplication cycle, which may explain their synergistic interaction. In addition, AZT enhances certain immune functions that have been correlated with a positive IFN alfa response. Preliminary clinical trials indicate that antitumor responses in Kaposi's sarcoma are seen with dosages of IFN alfa as low as 4.5 x 10(6) units per day when combined with AZT. However, the combination of IFN alfa and AZT may also produce dose-limiting hematologic side effects; these effects may limit the usefulness of the drug combination. Strategies for ameliorating these toxicities through the use of additional agents are discussed.

  20. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    PubMed Central

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC

    2014-01-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

  1. Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).

    PubMed

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D'Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan A C

    2014-06-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North Ame