Reasons and predictors for antiretroviral therapy change among HIV-infected adults at South West Ethiopia.

PubMed

Mekonnen, Endalkachew; Workicho, Abdulhalik; Hussein, Nezif; Feyera, Teka

2018-06-05

This retrospective cohort study is aimed to assess reasons and predictors of regimen change from initial highly active antiretroviral therapy among 1533 Human Immunodeficiency virus-infected adult patients at the Jimma University Tertiary Hospital. One in two (47.7%) adults changed their antiretroviral therapy regimen. Patients who were above the primary level of education [Hazard ratio (HR) 1.241 (95% CI 1.070-1.440)] and with human immunodeficiency virus/tuberculosis co-infection [HR 1.405 (95% CI 1.156-1.708)] had the higher risk of regimen change than their comparator. Individuals on Efavirenz [HR 0.675 (95% CI 0.553-0.825)] and non-stavudine [HR 0.494 (95% CI 0.406-0.601)] based regimens had lower risk of regimen change.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

PubMed

Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred; Emery, Sean; Grund, Birgit; Sharma, Shweta; Avihingsanon, Anchalee; Cooper, David A; Fätkenheuer, Gerd; Llibre, Josep M; Molina, Jean-Michel; Munderi, Paula; Schechter, Mauro; Wood, Robin; Klingman, Karin L; Collins, Simon; Lane, H Clifford; Phillips, Andrew N; Neaton, James D

2015-08-27

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. The initiation of

Antiretroviral treatment start-time during primary SIV(mac) infection in macaques exerts a different impact on early viral replication and dissemination.

PubMed

Sellier, Pierre; Mannioui, Abdelkrim; Bourry, Olivier; Dereuddre-Bosquet, Nathalie; Delache, Benoit; Brochard, Patricia; Calvo, Julien; Prévot, Sophie; Roques, Pierre

2010-05-11

The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. Six groups of macaques, infected intravenously with SIV(mac251), were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIV(mac251) exposure.

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

PubMed

Wright, Stephen T; Carr, Andrew; Woolley, Ian; Giles, Michelle; Hoy, Jennifer; Cooper, David A; Law, Matthew G

2011-09-01

To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.

Tinea Capitis in the form of Concentric Rings in an HIV Positive Adult on Antiretroviral Treatment

PubMed Central

Narang, Kirti; Pahwa, Manish; Ramesh, V

2012-01-01

Dermatophyte infection may present in the form of concentric rings caused by Trichophyton concentricum, known as Tinea Imbricata. In immunosuppressed patients, there are reports of lesions in the form of concentric rings caused by dermatophytes other than Trichophyton concentricum too, mostly by Trichophyton tonsurans, known as Tinea indesiciva or Tinea pseudoimbricata. We report a case of tinea capitis in a HIV-positive adult woman on antiretroviral therapy, who presented with concentric rings of papules and pustules with slight scaling on the scalp along with diffuse thinning of hair. Both Potassium hydroxide mount and culture showed the presence of Dermatophytes. Tinea capitis is considered rare in adults, but new cases are being reported in immunocompromised as well as in immunocompetent patients. The pertinent features of this case are: HIV-positive adult female on antiretroviral therapy, presenting with tinea capitis in the form of concentric rings; culture from the lesion grew Microsporum audouinii; responding to oral Terbinafine. PMID:22837564

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

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

New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per

Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

PubMed Central

Suthar, Amitabh B.; Lawn, Stephen D.; del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R.; Chaisson, Richard E.; Williams, Brian G.; Harries, Anthony D.; Granich, Reuben M.

2012-01-01

Background Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. Methods and Findings PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis

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

Dietary diversity and associated factors among HIV positive adults attending antiretroviral therapy clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia.

PubMed

Weldegebreal, Fitsum; Digaffe, Tesfaye; Mesfin, Frehiwot; Mitiku, Habtamu

2018-01-01

Nutritional care is considered a crucial component of comprehensive care for people living with HIV/AIDS (PLWHA), particularly in resource-limited settings where malnutrition and food insecurity are endemic problems, and low quality monotonous diets are the norm. The findings of this study provide baseline information on dietary diversity and related factors for health care providers so that they will be able to improve nutritional care and support activity. Therefore, the aim of this study was to assess dietary diversity and associated factors among HIV positive adults (18-65 years old) attending antiretroviral therapy (ART) clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia. An institution-based cross-sectional study was conducted from November 2015 to February 2016 at the ART clinics of Hiwot Fana and Dilchora Hospitals. Using a systematic random sampling technique, a total of 303 patients were selected from all adults attending the ART clinics. The data were collected with a 95% CI used to show association between dietary diversity and independent factors. A total of 303 adult HIV positive individuals on ART participated in the study and 62.4% were females. The largest numbers of participants (49.5%) were 30-40 years of age. Eighty-seven (28.7%) participants had low dietary diversity (≤4 food groups). Duration of anti-retroviral treatment was the factor significantly associated with dietary diversity: respondents with a duration of antiretroviral treatment of more than 2 years were almost two times more likely to have high dietary diversity compared with those with less than a year of antiretroviral treatment (adjusted odds ratio =0.490; 95% CI: 0.091, 0.978). Low dietary diversity was found to be a nutritional problem among HIV positive adults. Duration of antiretroviral treatment was the predictor of low dietary diversity. Therefore, appropriate dietary management of side effects of ART is important.

CD4/CD8 ratio, age, and risk of serious non-communicable diseases in HIV-infected adults on antiretroviral therapy

PubMed Central

CASTILHO, Jessica L.; SHEPHERD, Bryan E.; KOETHE, John; TURNER, Megan; BEBAWY, Sally; LOGAN, James; ROGERS, William B.; RAFFANTI, Stephen; STERLING, Timothy R.

2015-01-01

Objective In virologically suppressed HIV-infected adults, non-communicable diseases (NCDs) have been associated with immune senescence and low CD4/CD8 lymphocyte ratio. Age differences in the relationship between CD4/CD8 ratio and NCDs have not been described. Design Observational cohort study. Methods We assessed CD4/CD8 ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998–2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4/CD8 ratio and used Cox proportional hazard models to assess baseline CD4/CD8 ratio and NCDs. Results This study included 2,006 patients. Low baseline CD4/CD8 ratio was associated with older age, male sex, and low CD4 lymphocyte counts. In models adjusting for CD4 lymphocyte count, CD4/CD8 ratio was inversely associated with age (p <0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4/CD8 ratio was inversely associated with risk of CAD events (adjusted HR per 0.1 increase in CD4/CD8 ratio = 0.87, 95% CI: 0.76–0.99, p=0.03). This association was driven by those under age 50 years (adjusted HR 0.83 [0.70–0.97], p = 0.02) versus those over age 50 years (adjusted HR = 0.96 [0.79–1.18], p = 0.71). CD4/CD8 ratio was not significantly associated with incident non-cardiac NCDs. Conclusions Higher CD4/CD8 ratio after one year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy. PMID:26959354

Reported consent processes and demographics: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

PubMed

Denning, E; Sharma, S; Smolskis, M; Touloumi, G; Walker, S; Babiker, A; Clewett, M; Emanuel, E; Florence, E; Papadopoulos, A; Sánchez, A; Tavel, J; Grady, C

2015-04-01

Efforts are needed to improve informed consent of participants in research. The Strategic Timing of AntiRetroviral Therapy (START) study provides a unique opportunity to study the effect of length and complexity of informed consent documents on understanding and satisfaction among geographically diverse participants. Interested START sites were randomized to use either the standard consent form or the concise consent form for all of the site's participants. A total of 4473 HIV-positive participants at 154 sites world-wide took part in the Informed Consent Substudy, with consent given in 11 primary languages. Most sites sent written information to potential participants in advance of clinic visits, usually including the consent form. At about half the sites, staff reported spending less than an hour per participant in the consent process. The vast majority of sites assessed participant understanding using informal nonspecific questions or clinical judgment. These data reflect the interest of START research staff in evaluating the consent process and improving informed consent. The START Informed Consent Substudy is by far the largest study of informed consent intervention ever conducted. Its results have the potential to impact how consent forms are written around the world. © 2015 British HIV Association.

Impact of genetic factors on dyslipidemia in HIV-infected patients starting antiretroviral therapy.

PubMed

Egaña-Gorroño, Lander; Martínez, Esteban; Cormand, Bru; Escribà, Tuixent; Gatell, Jose; Arnedo, Mireia

2013-02-20

The impact of host genetic factors on the incidence of dyslipidemia in antiretroviral-naive HIV patients starting antiretroviral therapy (ART) is not clear. We assessed the role of single nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies adjusting for the contribution of nongenetic factors. We assessed 192 SNPs in an HIV cohort who started ART (1997-2008) including a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (NNRTI). Patients had fasting plasma lipids, total cholesterol (T-Chol), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides measured prior to their ART initiation and after 1 year. A logistic regression model was constructed and multiple test was corrected using 10% false discovery rate (FDR). Haplotypes and gene interactions were analysed. A total of 727 individuals were successfully genotyped (n = 381_PI-group; n = 346_NNRTI-group). Age and hepatitis C virus (HCV) coinfection were associated with increases and decreases in T-Chol and LDL-C (P < 0.01), respectively. Protease inhibitor containing ART showed an unfavourable association with T-Chol (P < 0.01) and triglycerides (P = 7.4E-4) and NNRTI-containing ART was favourably associated with HDL-C (P < 0.01). Moreover, SNPs in apolipoprotein B (APOB) were associated with an increase of LDL-C [rs10495712 (P = 3.18E-4); rs754524 (P = 1.26E-3)]. Six SNPs in three genes showed an association with a favourable effect on HDL-C levels when ART included NNRTI: ABCA1 (rs4149313, P = 2.97E-4), LIPC (rs1800588, P = 2.13E-3; rs473224, P = 3.06E-4; rs261336, P = 2.23E-3) and CETP (rs173539, P = 2.96E-3; rs3764261, P = 1.52E-3). After 10% FDR correction for multiple testing, one and six SNPs displayed significant associations with LDL-C and HDL-C, respectively. In HIV-infected patients staring ART, one SNP in APOB was associated with an increase

Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine co-administered with antiretroviral therapy in malaria-uninfected HIV-positive Malawian adults.

PubMed

Banda, Clifford G; Dzinjalamala, Fraction; Mukaka, Mavuto; Mallewa, Jane; Maiden, Victor; Terlouw, Dianne J; Lalloo, David G; Khoo, Saye H; Mwapasa, Victor

2018-05-21

There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus infected (HIV+) individuals taking antiretroviral therapy (ART). In a two step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared area under the concentration-time curve (AUC 0-28 days ) and safety outcomes of piperaquine among malaria-uninfected HIV+ adults. In step 1, half the adult dose of DHA-PQ was administered for three days as an intitial safety check in four groups (n=6/group) of HIV+ adults (age≥18 years): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART, and (iv) on ritonavir-boosted lopinavir-based ART. In step 2, a full adult treatment course of DHA-PQ was administered to a different cohort of participants in three groups: (i) antiretroviral naïve, (ii) on efavirenz-based ART and (iii) on nevirapine-based ART (n=10-15/group). Ritonavir-boosted lopinavir-based ART group was dropped in step 2 due to limited number of participants who were on this second line ART and were eligible for recruitment. Piperaquine's AUC 0-28 days in both steps was 43% lower among participants on efavirenz-based ART compared to ART naïve participants. There were no significant differences in AUC 0-28 days between the other ART groups and the ART naïve group in each of the two steps. Furthermore, no differences in treatment-emergent clinical and laboratory adverse events were observed across the groups in steps 1 and 2. Although well tolerated at half and full standard adult treatment courses, efavirenz based antiretroviral regimen was associated with reduced piperaquine exposure which may compromise dihydroartemisinin-piperaquine's effectiveness in programmatic settings. Copyright © 2018 Banda et al.

Effects on anthropometry and appetite of vitamins and minerals given in lipid nutritional supplements for malnourished HIV-infected adults referred for antiretroviral therapy: results from the NUSTART randomized controlled trial.

PubMed

Rehman, Andrea M; Woodd, Susannah; PrayGod, George; Chisenga, Molly; Siame, Joshua; Koethe, John R; Heimburger, Douglas C; Kelly, Paul; Friis, Henrik; Filteau, Suzanne

2015-04-01

The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery. The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART. Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference. Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite.

Information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS.

PubMed

Lima, Ivana Cristina Vieira de; Galvão, Marli Teresinha Gimeniz; Alexandre, Herta de Oliveira; Lima, Francisca Elisângela Teixeira; Araújo, Thelma Leite de

2016-08-01

Information and communication technologies support interventions directed at the prevention of HIV transmission and patient monitoring by promoting improved accessibility and quality of care. To evaluate the efficacy of information and communication technologies in the adherence to antiretroviral treatment in adults with HIV/AIDS. Systematic review conducted from March to May of 2015 in three databases-the Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Latin-American and Caribbean Literature in Health Sciences (LILACS/BIREME) and SCOPUS; and the Cochrane library and the Medical Literature Analysis and Retrieval System Online portal (MEDLINE/PubMed). The sample consisted of nine randomized clinical trials based on the use of information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS. Three studies analysed the use of a short message service - SMS - two phone calls, two alarm devices, one web-enabled Hand-held device and one web electronic intervention. Improvements in the levels of adherence in the group subjected to the intervention were identified in seven studies. The phone was the type of information and communication technology with proven efficacy with respect to adherence. It was used to make calls, as well as to send alert messages and reminders about taking medications. Pagers were not considered to be effective regarding adherence to antiretroviral therapy. The integrated use of information and communication technologies with standard care promotes increased access to care, strengthening the relationship between patients and health services, with the possibility of mitigating the difficulties experienced by people with HIV in achieving optimal levels of adherence to drug therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

PubMed

Janssens, Bart; Raleigh, Brian; Soeung, Seithaboth; Akao, Kazumi; Te, Vantha; Gupta, Jitendra; Vun, Mean Chhy; Ford, Nathan; Nouhin, Janin; Nerrienet, Eric

2007-11-01

Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

PubMed

Benjamin, Laura A; 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

2016-01-26

To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. 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. 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/mm(3), 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. 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. © 2015 American Academy of Neurology.

Effects on Anthropometry and Appetite of Vitamins and Minerals Given in Lipid Nutritional Supplements for Malnourished HIV-Infected Adults Referred for Antiretroviral Therapy: Results From the NUSTART Randomized Controlled Trial

PubMed Central

Rehman, Andrea M.; Woodd, Susannah; PrayGod, George; Chisenga, Molly; Siame, Joshua; Koethe, John R.; Heimburger, Douglas C.; Kelly, Paul; Friis, Henrik

2015-01-01

Background: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. Objective: We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery. Design: The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m2 received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART. Results: Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference. Conclusions: Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite. PMID:25501607

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.

New Antiretroviral Therapies for Pediatric HIV Infection

PubMed Central

Morris, Jennifer L.; Kraus, Donna M.

2005-01-01

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception.

PubMed

Mandelbrot, Laurent; Tubiana, Roland; Le Chenadec, Jerome; Dollfus, Catherine; Faye, Albert; Pannier, Emmanuelle; Matheron, Sophie; Khuong, Marie-Aude; Garrait, Valerie; Reliquet, Veronique; Devidas, Alain; Berrebi, Alain; Allisy, Christine; Elleau, Christophe; Arvieux, Cedric; Rouzioux, Christine; Warszawski, Josiane; Blanche, Stéphane

2015-12-01

The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2). Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

PubMed

Angeletti, C; Pezzotti, P; Antinori, A; Mammone, A; Navarra, A; Orchi, N; Lorenzini, P; Mecozzi, A; Ammassari, A; Murachelli, S; Ippolito, G; Girardi, E

2014-03-01

Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines. © 2013 British HIV Association.

Early age at start of antiretroviral therapy associated with better virologic control after initial suppression in HIV-infected infants.

PubMed

Shiau, Stephanie; Strehlau, Renate; Technau, Karl-Günter; Patel, Faeezah; Arpadi, Stephen M; Coovadia, Ashraf; Abrams, Elaine J; Kuhn, Louise

2017-01-28

The report of the 'Mississippi baby' who was initiated on antiretroviral therapy (ART) within 30 h of birth and maintained viral suppression off ART for 27 months has increased interest in the timing of ART initiation early in life. We examined associations between age at ART initiation and virologic outcomes in five cohorts of HIV-infected infants and young children who initiated ART before 2 years of age in Johannesburg, South Africa. We compared those who initiated ART early (<6 months of age) and those who started ART late (6-24 months of age). Two primary outcomes were examined: initial response to ART in three cohorts and later sustained virologic control after achieving suppression on ART in two cohorts. We did not observe consistent differences in initial viral suppression rates by age at ART initiation. Overall, initial viral suppression rates were low. Only 31, 40.1, and 26.5% of early-treated infants (<6 months of age) in the three cohorts, respectively, were suppressed less than 50 copies/ml of HIV RNA 6 months after starting ART. We did observe better sustained virologic control after achieving suppression on ART among infants starting ART early compared with late. Children who started ART early were less likely to experience viral rebound (>50 copies/ml or >1000 copies/ml) than children who started late in both cohorts. These findings provide additional support for early initiation of ART in HIV-infected infants.

Predictors of Nonadherence to Antiretroviral Therapy among HIV-Infected Adults in Dar es Salaam, Tanzania.

PubMed

Muya, Aisa N; Geldsetzer, Pascal; Hertzmark, Ellen; Ezeamama, Amara E; Kawawa, Hawa; Hawkins, Claudia; Sando, David; Chalamilla, Guerino; Fawzi, Wafaie; Spiegelman, Donna

2015-01-01

Adherence rates of ≥95% to antiretroviral therapy (ART) are necessary to maintain viral suppression in HIV-infected individuals. We identified predictors of nonadherence to scheduled antiretroviral drug pickup appointments in a large HIV care and treatment program in Tanzania. We performed a prospective cohort study of 44, 204 HIV-infected adults on ART between November 2004 and September 2012. Multivariate generalized estimating equation for repeated binary data was used to estimate the relative risk and 95% confidence intervals of nonadherence. Nonadherence was significantly greater among patients with high CD4 counts, high body mass indices, males, younger patients, patients with longer durations on ART, and those with perceived low social support. Targeted interventions should be developed to improve ART adherence among healthier, younger, and more experienced patients who are on ART for longer durations within HIV care and treatment programs. Social support for patients on ART should be emphasized. © The Author(s) 2014.

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

PubMed

Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

2012-07-31

For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

PubMed Central

Maganga, Emmanuel; Smart, Luke R.; Kalluvya, Samuel; Kataraihya, Johannes B.; Saleh, Ahmed M.; Obeid, Lama; Downs, Jennifer A.; Fitzgerald, Daniel W.; Peck, Robert N.

2015-01-01

Introduction Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune

Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia—a new context for refeeding syndrome?

PubMed Central

Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C

2009-01-01

High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries. PMID:21686792

Project Re-Start. A Program for Homeless Adults.

ERIC Educational Resources Information Center

Pelzer, Dagmar F.; And Others

Project Re-Start, of the Dade County Public Schools in Florida, was funded under the Adult Education Act and the Stewart B. McKinney Homeless Assistance Act. Classes in literacy skills, General Educational Development (GED) preparation, English for speakers of other languages, employability skills, and life coping skills were conducted at most of…

Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.

PubMed

Hammer, Scott M; Eron, Joseph J; Reiss, Peter; Schooley, Robert T; Thompson, Melanie A; Walmsley, Sharon; Cahn, Pedro; Fischl, Margaret A; Gatell, Jose M; Hirsch, Martin S; Jacobsen, Donna M; Montaner, Julio S G; Richman, Douglas D; Yeni, Patrick G; Volberding, Paul A

2008-08-06

The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial

Cost-Effectiveness of Earlier Initiation of Antiretroviral Therapy for Uninsured HIV-Infected Adults

PubMed Central

Schackman, Bruce R.; Goldie, Sue J.; Weinstein, Milton C.; Losina, Elena; Zhang, Hong; Freedberg, Kenneth A.

2001-01-01

Objectives. This study was designed to examine the societal cost-effectiveness and the impact on government payers of earlier initiation of antiretroviral therapy for uninsured HIV-infected adults. Methods. A state-transition simulation model of HIV disease was used. Data were derived from the Multicenter AIDS Cohort Study, published randomized trials, and medical care cost estimates for all government payers and for Massachusetts, New York, and Florida. Results. Quality-adjusted life expectancy increased from 7.64 years with therapy initiated at 200 CD4 cells/μL to 8.21 years with therapy initiated at 500 CD4 cells/μL. Initiating therapy at 500 CD4/μL was a more efficient use of resources than initiating therapy at 200 CD4/μL and had an incremental cost-effectiveness ratio of $17 300 per quality-adjusted life-year gained, compared with no therapy. Costs to state payers in the first 5 years ranged from $5500 to $24 900 because of differences among the states in the availability of federal funds for AIDS drug assistance programs. Conclusions. Antiretroviral therapy initiated at 500 CD4 cells/μL is cost-effective from a societal perspective compared with therapy initiated later. States should consider Medicaid waivers to expand access to early therapy. PMID:11527782

Current CD4 cell count and the short-term risk of AIDS and death before the availability of effective antiretroviral therapy in HIV-infected children and adults.

PubMed

Dunn, David; Woodburn, Patrick; Duong, Trinh; Peto, Julian; Phillips, Andrew; Gibb, Di; Porter, Kholoud

2008-02-01

Currently, there are no comparable estimates of the short-term risk of disease progression in the absence of effective antiretroviral therapy for human immunodeficiency virus (HIV)-infected adults and children. A joint analysis of 2 large studies of children with vertically acquired HIV infection (the HIV Paediatric Prognostic Markers Collaborative Study) and adults with seroconversion (the CASCADE [Concerted Action on Sero-Conversion to AIDS and Death in Europe] collaboration) was conducted. Follow-up was censored at the end of 1995, before the introduction of combination antiretroviral therapy. The incidence rates of death and AIDS or death (AIDS/death) were estimated on the basis of age and current CD4 cell count. A total of 1260 deaths (over 20,500 person-years of follow-up) and 1894 initial AIDS events (over 17,200 person-years of follow-up) were observed among 6741 patients (3244 children [i.e., patients < or =15 years of age] and 3497 adults). Young children (age, <5 years) experienced high morbidity and mortality rates. After adjustment for the CD4 cell count, the effect of age on disease progression was not significant among older children, whereas the risk increased markedly in association with increasing age among adults. Death rates were similar among older children and adults aged approximately 20 years, as were the rates of progression to AIDS/death when cases of serious recurrent bacterial infection, which has a more restrictive case definition in adults, were excluded. Similar CD4 cell count criteria for initiation of antiretroviral therapy can be applied to adults and children > or = 5 years of age.

Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia

PubMed Central

Mulenga, Lloyd B.; Kruse, Gina; Lakhi, Shabir; Cantrell, Ronald A.; Reid, Stewart E.; Zulu, Isaac; Stringer, Elizabeth M.; Krishnasami, Zipporah; Mwinga, Alwyn; Saag, Michael S.; Stringer, Jeffrey S. A.; Chi, Benjamin H.

2009-01-01

Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment. PMID:18753939

Endothelial Function in HIV-Infected Antiretroviral Naïve Subjects Before and After Starting Potent Antiretroviral Therapy: AIDS Clinical Trials Group Study 5152s

PubMed Central

Torriani, Francesca J.; Komarow, Lauren; Parker, Robert A.; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Stein, James H.

2008-01-01

Objectives This study evaluated the effects of three class-sparing antiretroviral therapy (ART) regimens on endothelial function in HIV-infected subjects participating in a randomized trial. Background Endothelial dysfunction has been observed in patients receiving ART for human immunodeficiency virus (HIV) infection. Methods This was a prospective, multicenter study of treatment-naïve subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks. Results There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV RNA values were 245 cells/mm3 and 4.8 log10 copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range 1.98 – 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log10 copies/mL, respectively. FMD increased by 0.74% (−0.62 – +2.74, p=0.003) and 1.48% (−0.20 – +4.30%, p< 0.001), respectively, with similar changes in each arm (pKW>0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (rs=− 0.30, p=0.017). Conclusions Among treatment-naïve individuals with HIV, three different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks. Condensed Abstract Among 82 treatment-naïve HIV-infected subjects participating in a prospective, multicenter study of three class-sparing antiretroviral therapy regimens, flow-mediated dilation of the brachial artery improved after 4 (+0.74%, p=0.003) and 24 weeks (+1.48%, p< 0

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

PubMed

Baker, Jason V; Sharma, Shweta; Achhra, Amit C; Bernardino, Jose Ignacio; Bogner, Johannes R; Duprez, Daniel; Emery, Sean; Gazzard, Brian; Gordin, Jonathan; Grandits, Greg; Phillips, Andrew N; Schwarze, Siegfried; Soliman, Elsayed Z; Spector, Stephen A; Tambussi, Giuseppe; Lundgren, Jens

2017-05-22

HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4 + cell counts >500 cells/mm 3 . Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm 3 , an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in

Why are HIV-infected people not started on antiretroviral therapy? A mixed-methods study from Gujarat, India

PubMed Central

Shringarpure, K.; Modi, B.; Sharma, R.; Rewari, B. B.; Shah, A. N.; Verma, P. B.; Dongre, A. R.; Kumar, A. M. V.

2017-01-01

Setting: Five purposively selected antiretroviral therapy (ART) centres in Gujarat, India. Objectives: To assess the proportion of ART-eligible people living with the human immunodeficiency virus (PLHIV) who were not initiated on ART within 2 months of being recorded as eligible, to identify factors associated with non-initiation and to explore reasons from the provider's perspective. Design: We used a mixed-methods design (triangulation) of 1) a quantitative phase involving record reviews and cohort analysis (Poisson regression) of PLHIV registered during April 2014–March 2015, and 2) a qualitative phase involving one-to-one interviews with 25 providers. Results: Of 2079 ART-eligible PLHIV, 339 (16%) were not started on ART within 2 months. PLHIV with CD4 counts of <350 cells/μl and patients who were labourers, hospitalised, bedridden or registered with certain ART centres were more likely not to be initiated on ART. Qualitative results were categorised into two broad themes: government health system- and patient-related challenges, which validated and complemented the quantitative findings. Conclusion: Several patient subgroups at greater risk of ART non-initiation were identified, along with reasons for risk; this has important programme implications for achieving the UNAIDS 90–90–90 goal, and particularly the second 90 component of having 90% of diagnosed PLHIV start ART. PMID:29201653

Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

PubMed

Grarup, J; Rappoport, C; Engen, N W; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, M J

2015-04-01

The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem-solving. © 2015 British HIV Association.

Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

PubMed Central

Rappoport, C; Engen, NW; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, MJ

2015-01-01

Objectives The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. Methods START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. Results An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Conclusions Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem‐solving. PMID:25711319

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

PubMed

Olsen, Mette F; 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, Ase B; Friis, Henrik

2014-05-15

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. Randomised controlled trial. Three public ART facilities in Jimma, Oromia region, Ethiopia. Adults with HIV eligible for ART with body mass index (BMI) >16. 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. 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. 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 significantly different in direct comparison. Exploratory analysis showed that relatively

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

'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe.

PubMed

Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirigh, Conall; Chibanda, Dixon; Abas, Melanie

2015-07-01

To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy. © 2015 John Wiley & Sons Ltd.

Potential drug interactions in patients given antiretroviral therapy

PubMed Central

dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-01-01

ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. PMID:27878224

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

PubMed

Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2016-07-01

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

PubMed

Floridia, Marco; Ciccacci, Fausto; Andreotti, Mauro; Hassane, Archa; Sidumo, Zita; Magid, Nurja A; Sotomane, Horacio; David, Muhlavasse; Mutemba, Elsa; Cebola, Junia; Mugunhe, Remigio Josè; Riccardi, Fabio; Marazzi, Maria Cristina; Giuliano, Marina; Palombi, Leonardo; Mancinelli, Sandro

2017-11-13

Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation

One-year outcomes of women started on antiretroviral therapy during pregnancy before and after the implementation of Option B+ in Malawi: A retrospective chart review.

PubMed

Kamuyango, Alfred A; Hirschhorn, Lisa R; Wang, Wenjia; Jansen, Perry; Hoffman, Risa M

2014-09-01

To compare one-year outcomes of women started on antiretroviral therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+ era. A retrospective chart review was performed at three sites in Malawi. Women were included in the 'pre-Option B+' cohort if they started ART during pregnancy for a CD4 count < 350 cells/mm 3 or WHO 3/4 condition and in the 'Option B+' cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA F-tests. A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.

“I was thinking too much”: experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe

PubMed Central

Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirgh, Conall; Chibanda, Dixon; Abas, Melanie

2015-01-01

Objective To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. Methods In-depth qualitative interviews were conducted with 47 (female =31) HIV-positive adults who scored above the cut-point on a locally-validated scale for common mental disorders. Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. Results The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of common mental disorders (“thinking too much”, changes to appetite and sleep, “burdened heart”, and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with common mental disorders. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income generating activities, and family engagement in mental health care. Conclusions Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce common mental disorders and poor adherence to antiretroviral therapy. PMID:25754063

Cardiovascular risk in advanced naïve HIV-infected patients starting antiretroviral therapy: Comparison of three different regimens - PREVALEAT II cohort.

PubMed

Maggi, Paolo; Bellacosa, Chiara; Leone, Armando; Volpe, Anna; Ricci, Elena Delfina; Ladisa, Nicoletta; Cicalini, Stefania; Grilli, Elisabetta; Viglietti, Rosaria; Chirianni, Antonio; Bellazzi, Lara Ines; Maserati, Renato; Martinelli, Canio; Corsi, Paola; Celesia, Benedetto Maurizio; Sozio, Federica; Angarano, Gioacchino

2017-08-01

PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy. Our primary objective was to evaluate changes in carotid intima- media thickness (IMT). Secondary endpoints included changes in flow mediated vasodilation (FMD), inflammatory markers, triglycerides and cholesterol. Patients were evaluated at time 0, and after 3, 6 and 12 months. We enrolled 119 patients, stratified into three different groups: patients receiving atazanavir/ritonavir boosted (ATV/r) based regimens, efavirenz (EFV) based regimens and darunavir/ritonavir boosted (DRV/r) based regimens. At baseline, advanced naïve patients showed a relevant deterioration of CV conditions in terms of traditional CV risk factors, endothelial dysfunction and serum biomarkers. During the 12-month follow up period, mean blood lipids significantly increased: total cholesterol from 159 to 190 mg/dL, HDL-C from 31 to 41 mg/dL, and LDL-C from 99 to 117 mg/dL. D-dimers steadily decreased (median level 624 at baseline and 214 at T3), whereas ICAM and VCAM consistently raised. DRV/r and ATV/r determined a more marked decrease of D-dimers as compared to EFV. Regarding the epi-aortic changes (IMT >1 mm or presence of atherosclerotic plaques), patients in the DRV/r group were at risk of developing pathological IMT during the study (OR 6.0, 95% CI 0.9-36.9), as compared to EFV ones. CV risk was elevated in advanced naïve patients and tended to remain high in the first year of therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network.

PubMed

Wolff, Marcelo; Shepherd, Bryan E; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Wagner Cardoso, Sandra; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C

2016-01-01

HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

PubMed

Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-05-17

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should

Non-adherence to anti-retroviral therapy among HIV infected adults in Mon State of Myanmar.

PubMed

Aye, Win Lei; Puckpinyo, Apa; Peltzer, Karl

2017-05-05

The provision of Anti-Retroviral Therapy (ART) was started in Myanmar in 2005 in collaboration with the National AIDS Program and the private sector. Successful clinical management of HIV-infected patients is subject to optimal adherence. The aim of the study was to determine the prevalence of adherence to ART and identify factors associated with non-adherence to ART among HIV infected adults registered in a private sector setting in Mon State, Myanmar. This cross-sectional study was conducted with adults living with HIV receiving ART at an HIV outpatient clinic between April and May 2016. A total of three hundred People Living with HIV(PLHIV) were interviewed using a pretested and structured questionnaire. The 30 days Visual Analog Scale (VAS) adherence instrument was used to assess the level of adherence. Multivariable logistic regression analysis was used to determine factors associated with non-adherence to ART. Among 300 patients (male 37.7% and female 62.3%, with a mean age of 41.3 years, standard deviation 8.7), 84% reported ≥95% adherence to ART in the past month. Among 16% of those reporting non-adherence, major reasons for skipping the medication were being busy (23%), being away from home (17.7%) and being forgetful (12.3%). In multivariable logistic rgeression, low behavioural skills on ART adherence (OR = 0.31, 95% CI: 0.10-0.94), tobacco use (OR = 3.22, 95% CI:1.28-8.12), having disclosed their HIV status (OR = 0.07, 95% CI: 0.01-0.69), having a partner who was not on ART (OR = 4.25, 95% CI: 1.70-10.64) and among men, having erectile dysfunction (OR = 15.14, 95% CI: 1.41-162.66) were significant associated with ART non-adherence. Non-adherence to ART was associated with individual moderating factors and behavioral skills. Priority measures such as addressing risk behaviour and behavioural change communication tailored to individual patients' lifestyles requires comprehensive interventions to improve adherence.

One-year outcomes of women started on antiretroviral therapy during pregnancy before and after the implementation of Option B+ in Malawi: A retrospective chart review

PubMed Central

Kamuyango, Alfred A.; Hirschhorn, Lisa R; Wang, Wenjia; Jansen, Perry; Hoffman, Risa M.

2015-01-01

Objective To compare one-year outcomes of women started on antiretroviral therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods A retrospective chart review was performed at three sites in Malawi. Women were included in the ‘pre-Option B+’ cohort if they started ART during pregnancy for a CD4 count < 350 cells/mm3 or WHO 3/4 condition and in the ‘Option B+’ cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA F-tests. Results A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+. PMID:25774326

HIV Treatment and Prevention: An Overview of Recommendations From the 2016 IAS–USA Antiretroviral Guidelines Panel

PubMed Central

Volberding, Paul A.

2017-01-01

Updated recommendations from the IAS–USA Antiretroviral Guidelines Panel on antiretroviral therapy for the treatment and prevention of HIV infection in adults were published in the Journal of the American Medical Association in 2016. The updated, evidence-based recommendations address when to initiate antiretroviral therapy, recommended initial antiretroviral regimens, including integrase strand transfer inhibitor (InSTI)-based regimens, recommended regimens for persons in whom an InSTI is not an option, and special treatment considerations. The interface between antiretroviral therapy and opportunistic infections, when and how to switch antiretroviral therapy, laboratory monitoring, engagement in care, adherence to antiretroviral therapy, and use of antiretroviral therapy as HIV prevention are also discussed, as well as future directions in HIV treatment. This article summarizes an IAS–USA continuing education webinar presented by Paul A. Volberding, MD, in August 2016. PMID:28402930

Disclosure amongst adult HIV patients on antiretroviral therapy in Port Harcourt, Nigeria.

PubMed

Omunakwe, Hannah E; Okoye, Helen; Efobi, Chilota; Onodingene, Maryanne; Chinenye, Sunny; Nwauche, Chijioke A

2015-09-01

HIV transmission is still a public health concern in sub-Saharan Africa; disclosure is an effective tool for its prevention, contact tracing and treatment. We aimed to evaluate the disclosure behaviours of adult HIV-positive patients receiving antiretroviral therapy (ART) in University of Port Harcourt Teaching Hospital, and identify major challenges to disclosure in a bid to develop ways to improve this practice in the environment. Patients receiving ART in this centre were interviewed using an interviewer-administered questionnaire. A total of 250 clients were interviewed over three months. A majority of the patients were tested on account of ill health 143 (57.2%). They commenced ART within 8 ± 15.4 SD months of presentation. The mean period before disclosure was 4.75 ± 12.8 SD months of diagnosis. Thirty-six (14.4%) of the respondents had not disclosed their HIV status; the major barrier to disclosure was stigmatisation in 19 (36%). © The Author(s) 2014.

ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-INFECTED ADULTS IN THE UNITED STATES

PubMed Central

Beer, Linda; Skarbinski, Jacek

2015-01-01

National estimates of antiretroviral therapy (ART) adherence and adherence support services utilization are needed to inform efforts to improve the health of HIV-infected persons in the United States. In a nationally representative sample of HIV-infected adults receiving medical care, 86% self-reported taking all ART doses in the past 72 hours. Overall, 20% reported using adherence support services and 2% reported an unmet need for services. If all nonadherent persons not receiving adherence support and all persons with a self-perceived unmet need for adherence support accessed services, resources to support ~42,673 additional persons would be needed. Factors associated with lower adherence included younger age, female gender, depression, stimulant use, binge alcohol use, greater than once-daily dosing, longer time since HIV diagnosis, and patient beliefs. Predictors of adherence are multifactorial so multiple targeted strategies to improve adherence are warranted. Providing adherence support services to all those in need may require additional resources. PMID:25490733

Effects of secondary prophylaxis started in adolescent and adult haemophiliacs.

PubMed

Tagliaferri, A; Franchini, M; Coppola, A; Rivolta, G F; Santoro, C; Rossetti, G; Feola, G; Zanon, E; Dragani, A; Iannaccaro, P; Radossi, P; Mannucci, P M

2008-09-01

While primary prophylaxis is a well-established and recommended method of care delivery for children with severe haemophilia, fewer studies have documented the benefits of secondary prophylaxis started in adolescence or adulthood. To evaluate the role of secondary prophylaxis started in adolescent and adult severe haemophiliacs, a retrospective observational cohort study was conducted in 10 Italian Centres that investigated 84 haemophiliacs who had bled frequently and had thus switched from on-demand to prophylactic treatment during adolescence (n = 30) or adulthood (n = 54). The consumption of clotting factor concentrates, the orthopaedic and radiological scores, quality of life and disease-related morbidity were compared before and after starting secondary prophylaxis. Prophylaxis reduced the mean annual number of total and joint bleeds (35.8 vs. 4.2 and 32.4 vs. 3.3; P < 0.01) and of days lost from work/school (34.6 vs. 3.0, P < 0.01). A statistically significant reduction in the orthopaedic score was observed during prophylaxis in adolescents, but not in the whole cohort. Patients used more factor concentrates with corresponding higher costs on prophylaxis, but experienced a better quality of life. With respect to on-demand treatment, higher factor consumption and cost of secondary prophylaxis were balanced by marked clinical benefits and greater well-being in this cohort of adolescent/adult haemophiliacs.

No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts.

PubMed

Wright, Edwina J; Grund, Birgit; Robertson, Kevin R; Cysique, Lucette; Brew, Bruce J; Collins, Gary L; Poehlman-Roediger, Mollie; Vjecha, Michael J; Penalva de Oliveira, Augusto César; Standridge, Barbara; Carey, Cate; Avihingsanon, Anchalee; Florence, Eric; Lundgren, Jens D; Arenas-Pinto, Alejandro; Mueller, Nicolas J; Winston, Alan; Nsubuga, Moses S; Lal, Luxshimi; Price, Richard W

2018-05-15

To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/μl. Randomized trial. The START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/μl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. The 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/μl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P < 0.001 for increase from baseline). We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4 cell counts above 500 cells/μl.

An update and review of antiretroviral therapy.

PubMed

Piacenti, Frank J

2006-08-01

The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis.

PubMed

Girardi, Enrico; Scognamiglio, Paola; Angeletti, Claudio; Gori, Andrea; Buonfrate, Dora; Arlotti, Massimo; Mazzarello, Giovanni; Castagna, Antonella; Andreoni, Massimo; d'Arminio Monforte, Antonella; Antinori, Andrea; Ippolito, Giuseppe

2012-02-15

Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with

Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

PubMed Central

Boulle, Andrew; Schomaker, Michael; May, Margaret T.; Hogg, Robert S.; Shepherd, Bryan E.; Monge, Susana; Keiser, Olivia; Lampe, Fiona C.; Giddy, Janet; Ndirangu, James; Garone, Daniela; Fox, Matthew; Ingle, Suzanne M.; Reiss, Peter; Dabis, Francois; Costagliola, Dominique; Castagna, Antonella; Ehren, Kathrin; Campbell, Colin; Gill, M. John; Saag, Michael; Justice, Amy C.; Guest, Jodie; Crane, Heidi M.; Egger, Matthias; Sterne, Jonathan A. C.

2014-01-01

Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and

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

PubMed

2018-05-11

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

Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort

PubMed Central

Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

2013-01-01

Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID:22778335

“Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”

PubMed Central

Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

2013-01-01

OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

Lack of pre-antiretroviral care and competition from traditional healers, crucial risk factors for very late initiation of antiretroviral therapy for HIV--a case-control study from eastern Uganda.

PubMed

Muhamadi, Lubega; Tumwesigye, Nazarius Mbona; Kadobera, Daniel; Marrone, Gaetano; Wabwire-Mangen, Fred; Pariyo, George; Peterson, Stefan; Ekström, Anna Mia

2011-01-01

Although WHO recommends starting antiretroviral treatment at a CD4 count of 350 cells/[µ]L, many Ugandan districts still struggle with large proportions of clients initiating ART very late at CD4<50 cells/[µ]L. This study seeks to establish crucial risk factors for very late ART initiation in eastern Uganda. All adult HIV-infected clients on ART in Iganga who enrolled between 2005 and 2009 were eligible for this case-control study. Clients who started ART at CD4 cell count of <50 cells/[µ]L (very late initiators) were classified as cases and 50-200 cells/[µ]L (late initiators) as control subjects. A total of 152 cases and 202 controls were interviewed. Multivariate analyses were performed to calculate adjusted odds ratios and 95% confidence intervals. Reported health system-related factors associated with very late ART initiation were stock-outs of antiretroviral drugs stock-outs (affecting 70% of the cases and none of the controls), competition from traditional/spiritual healers (AOR 7.8, 95 CI% 3.7-16.4), and lack of pre-ARV care (AOR 4.6, 95% CI: 2.3-9.3). Men were 60% more likely and subsistence farmers six times more likely (AOR 6.3, 95% CI: 3.1-13.0) to initiate ART very late. Lack of family support tripled the risk of initiating ART very late (AOR 3.3, 95% CI: 1.6-6.6). Policy makers should prevent ARV stock-outs though effective ARV procurement and supply chain management. New HIV clients should seek pre-ARV care for routine monitoring and determination of ART eligibility. ART services should be more affordable, accessible and user-friendly to make them more attractive than traditional healers.

Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

PubMed Central

Inzaule, Seth C.; Hamers, Raph L.; Kityo, Cissy; Rinke de Wit, Tobias F.; Roura, Maria

2016-01-01

Background Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. Methods We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. Results The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Conclusion Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints

Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy: A Prospective Cohort Study.

PubMed

Ezeamama, Amara E; Woolfork, Makhabele N; Guwatudde, David; Bagenda, Danstan; Manabe, Yukari C; Fawzi, Wafaie W; Smith Fawzi, Mary C

2016-03-01

The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up.QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time*depression P < 0.001) and anxiety levels (time*anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time*social support P = 0.8943) or number of stigmatizing experiences (time*stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults.

Antiretroviral treatment during pregnancy.

PubMed

Keiser, Olivia; Gayet-Ageron, Angèle; Rudin, Christoph; Brinkhof, Martin W G; Gremlich, Erika; Wunder, Dorothea; Drack, Gero; Hirschel, Bernard; de Tejada, Begoña Martinez

2008-11-12

Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Age Matters: Increased Risk of Inconsistent HIV Care and Viremia Among Adolescents and Young Adults on Antiretroviral Therapy in Nigeria

PubMed Central

Ahonkhai, Aimalohi A.; Banigbe, Bolanle; Adeola, Juliet; Adegoke, Abdulkabir B.; Regan, Susan; Bassett, Ingrid V.; Idigbe, Ifeoma; Losina, Elena; Okonkwo, Prosper; Freedberg, Kenneth A.

2016-01-01

Purpose Interruptions in HIV care are a major cause of morbidity and mortality, particularly in resource-limited settings. We compared engagement in care and virologic outcomes between HIV-infected adolescents and young adults (AYA) and older adults (OA) one year after starting antiretroviral therapy (ART) in Nigeria. Methods We conducted a retrospective cohort study of AYA (15–24 years) and OA (>24 years) who initiated ART from 2009–2011. We used negative binomial regression to model the risk of inconsistent care and viremia (HIV RNA >1,000 copies/mL) among AYA and OA in the first year on ART. Regular care included monthly ART pick-up and 3-monthly clinical visits. Patients with ≤3 months between consecutive visits were considered in care. Those with inconsistent care had >3 months between consecutive visits. Results The cohort included 354 AYA and 2,140 OA. More AYA than OA were female (89% vs. 65%, p<0.001). Median baseline CD4 was 252/µL in AYA and 204/µL in OA (p=0.002). More AYA had inconsistent care than OA (55% vs. 47%, p=0.001). Adjusting for sex, baseline CD4, and education, AYA had a greater risk of inconsistent care than OA (RR 1.11, p=0.033). Among those in care after one year on ART, viremia was more common in AYA than OA (40% vs. 26% p=0.003, RR 1.53, p=0.002). Conclusions In a Nigerian cohort, AYA were at increased risk for inconsistent HIV care. Of patients remaining in care, youth was the only independent predictor of viremia at 1 year. Youth-friendly models of HIV care are needed to optimize health outcomes. PMID:27329680

Could Early Antiretroviral Therapy Entail More Risks than Benefits in sub-Saharan African HIV-Infected Adults? A Model-Based Analysis

PubMed Central

Anglaret, Xavier; Scott, Callie A.; Walensky, Rochelle P.; Ouattara, Eric; Losina, Elena; Moh, Raoul; Becker, Jessica E.; Uhler, Lauren; Danel, Christine; Messou, Eugene; Eholié, Serge; Freedberg, Kenneth A.

2013-01-01

Background Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4 counts. Methods We used a simulation model to compare ART initiation upon entry to care (“immediate ART”) to initiation at CD4 ≤350 cells/μL (“WHO 2010 ART”) in African adults with CD4 counts >500 cells/μL. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. Results Fifteen-year mortality was 56.7% for WHO 2010 and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was >1.0/100PY, the rate of withdrawal from care was >1.2-fold higher or the rate of ART failure due to poor adherence was >4.3-fold higher on immediate ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100PY) were combined with rates of withdrawal from care >1.1-fold higher and rates of treatment failure >2.1-fold higher on immediate ART than on WHO 2010 ART. Conclusions In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4 counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be critical. PMID:22809695

In a study of a population cohort in South Africa, HIV patients on antiretrovirals had nearly full recovery of employment.

PubMed

Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

2012-07-01

Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the President's Emergency Plan for AIDS Relief. We linked clinical data from more than 2,000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of more than 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed-effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening HIV illness and the decision to seek care. There are large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

PubMed

Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

2014-11-01

Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial.

PubMed

Hosseinipour, Mina C; Bisson, Gregory P; Miyahara, Sachiko; Sun, Xin; Moses, Agnes; Riviere, Cynthia; Kirui, Fredrick K; Badal-Faesen, Sharlaa; Lagat, David; Nyirenda, Mulinda; Naidoo, Kogieleum; Hakim, James; Mugyenyi, Peter; Henostroza, German; Leger, Paul D; Lama, Javier R; Mohapi, Lerato; Alave, Jorge; Mave, Vidya; Veloso, Valdilea G; Pillay, Sandy; Kumarasamy, Nagalingeswaran; Bao, Jing; Hogg, Evelyn; Jones, Lynne; Zolopa, Andrew; Kumwenda, Johnstone; Gupta, Amita

2016-03-19

Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080. Between Oct 31, 2011, and June 9, 2014, we enrolled 850

The Perfect Pairing: The Adult Learner and the Boutique Winery in the Start-Up Phase

ERIC Educational Resources Information Center

Heath-Simpson, Delta F.

2011-01-01

The purpose of this phenomenological study was to understand and describe the lived experiences of adult learners who are owners and managers of small winery businesses operating in the start-up phase of the organizational life cycle. The study explored and identified the meaning of adult learning in the entrepreneurial context and its affect on…

Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

PubMed Central

Maskew, Mhairi; Fox, Matthew P.; van Cutsem, Gilles; Chu, Kathryn; MacPhail, Patrick; Boulle, Andrew; Egger, Matthias; Africa, for IeDEA Southern

2013-01-01

Background Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. Methods We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. Results Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm3) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm3) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment. Conclusions HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS

Factors Associated with Timing of Initiation of Antiretroviral Therapy among HIV-1 Infected Adults in the Niger Delta Region of Nigeria

PubMed Central

Ogoina, Dimie

2015-01-01

Introduction Based on growing evidence mainly from countries outside Sub-Saharan Africa, the World Health Organisation (WHO) now recommends initiation of antiretroviral therapy (ART) in HIV-infected individuals in developing countries when CD4 cell count (CD4+) is ≤ 500cells/ul. Nigeria accounts for about 14% of the estimated HIV/AIDS burden in Sub-Saharan Africa. We evaluated the factors associated with timing of initiation of ART among treatment-ineligible HIV-infected adults from Nigeria. Methods We retrospectively reviewed the hospital records of ART ineligible HIV-infected adults who enrolled into HIV care between January 2008 and December 2012 at two major tertiary hospitals in Bayelsa State, South-South Nigeria. Demographic, clinical and laboratories data were obtained at presentation, at each subsequent visit at 6 monthly intervals and at time of initiation of ART. Cox proportional regression and Kaplan-Meier survival analysis were used to evaluate independent predictors of time to initiation of ART. Results Amongst the 280 study participants, 70.6% were females, 62.6% had CD4+ ≥500cells/ul, 48.4% had WHO HIV Stage 1 disease and 34.3% were lost to follow up. In a cohort of 180 participants followed up for ≥3months, participants with CD4+ of 351-500cells/ul and stage 2 disease were more likely to start ART earlier than those with CD4+ > 500cells/ul (Hazard ratio [HR]-1.7, 95% confidence interval [CI] of 1.0-2.9) and stage 1 disease (HR-2.3 (95% CI-1.3-4.2) respectively. HIV-infected adults with faster CD4+ decay required earlier ART initiation, especially in the first year of follow up. Conclusion ART-ineligible HIV-infected adults on follow up in South-South Nigeria are more likely to require earlier initiation of ART if they have stage 2 HIV disease or CD4+ ≤500cells/ul at presentation. Our findings suggest faster progression of HIV-disease in these groups of individuals and corroborate the growing evidence in support for earlier initiation of ART

Antiretroviral therapy: current drugs.

PubMed

Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

PubMed

Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B

2015-11-01

Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy.

CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group Studies

PubMed Central

Tassiopoulos, Katherine; Landay, Alan; Collier, Ann C.; Connick, Elizabeth; Deeks, Steven G.; Hunt, Peter; Lewis, Dorothy E.; Wilson, Cara; Bosch, Ronald

2012-01-01

Background Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks. Methods We measured the percentage of CD28−CD4+ and CD8+ T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment %CD28− cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection. Results In total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher %CD28−CD4+ and %CD28−CD8+ cells. For CD8+ cells, younger age and HCV infection were associated with a lower %CD28−. ART reduced %CD28− levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher %CD28−CD8+. Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28−. Conclusions Effective ART reduced the proportion of CD28− T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults. PMID:22448010

Food insecurity and antiretroviral adherence among HIV positive adults who drink alcohol.

PubMed

Kalichman, Seth C; Grebler, Tamar; Amaral, Christina M; McKerney, Megan; White, Denise; Kalichman, Moira O; Cherry, Chauncey; Eaton, Lisa

2014-10-01

Food insecurity is associated with HIV treatment non-adherence and poor health outcomes for people living with HIV/AIDS. Given the poor nutritional status common to people who drink alcohol, food insecurity may be particularly problematic for HIV positive individuals who drink alcohol. To examine food insecurity among HIV positive men and women who drink alcohol and its association with antiretroviral therapy (ART) adherence, health outcomes and health service utilization. Adults living with HIV (N = 183) in Atlanta, Georgia who reported alcohol use in the previous week and were receiving ART participated in a 12-month cohort. Participants were recruited from infectious disease clinics and social services to complete computerized interviews, monthly-unannounced pill counts to monitor ART adherence, and daily cell-phone delivered interactive-text assessments for alcohol use. Forty-three percent of participants experienced food insecurity during at least one month of the study period. Food insecurity was independently associated with suboptimal ART adherence and less suppressed HIV viral load over. Individuals who experienced food insecurity also had histories of more medical and psychiatric hospitalizations, and greater mental health problems. Food insecurity is prevalent among alcohol using people receiving ART and food insecurity is associated with treatment non-adherence, poor health outcomes, and increased medical and psychiatric hospitalizations.

iSTART-ALL: Confronting Adult Low Literacy with Intelligent Tutoring for Reading Comprehension

ERIC Educational Resources Information Center

Johnson, Amy M.; Guerrero, Tricia A.; Tighe, Elizabeth L.; McNamara, Danielle S.

2017-01-01

There is little empirical research available on the substantial problem of adult low literacy rates, and limited educational technologies are available to address distinct instructional needs of this population. This paper reports on development and testing of a version of Interactive Strategy Training for Active Reading and Thinking (iSTART) for…

Comparison of survival in adult antiretroviral treatment naïve patients treated in primary health care centers versus those treated in hospitals: retrospective cohort study; Oromia region, Ethiopia.

PubMed

Megerso, Abebe; Garoma, Sileshi

2016-10-18

Antiretroviral treatment (ART) service scaling up has been practiced in the Ethiopia since 2006. Regardless of increasing number of primary health care centers providing the service, the existing hospitals are still overcrowded with ART service seeking patients may be because of the common belief that treatment outcome is better for hospital patients than those treated at the primary health centers. However, documented evidence comparing the treatment outcome for the two categories of health facilities is scarce in the study setting. The purpose of the current study was to compare major treatment outcomes among new patients treated at the two health facility categories. Retrospective cohort study was implemented using secondary data from medical records collected between October 2010 and January 2014 in the selected health facilities. All patients (1895) who started the treatment in the facilities during the period were included in the study. Univariate analyses were made using descriptive methods such as frequency distributions and measures of central tendency. Bivariate and multivariate analyses were made using Kaplan Meier and Cox regression models respectively to compare the mean survival time between the two facility categories. P-value less than 0.05 was considered as statistically significant. A total of 1895 patient records were followed for 27,990 person-months. Risks of unwanted treatment outcomes (death and lose-to-follow-up) were the same for both categories of patients. The median survival probability was similar to the facility categories (P-value = 0.11). Baseline performance scale III/IV (AHR, 2.4; 95 % CI: 2.0, 3.0), baseline WHO clinical stages III/IV (AHR, 2.8; 95 % CI: 2.3, 3.4), and low adherence (<95 %) to ART drugs (AHR, 3.4; 95 % CI: 2.8, 5.2) were the independent predictors of the unwanted treatment outcomes. Antiretroviral treatment service delivery at primary health care facilities did not compromise the treatment outcomes among

Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland.

PubMed

Bock, Naomi N; Emerson, Ruth C; Reed, Jason B; Nkambule, Rejoice; Donnell, Deborah J; Bicego, George T; Okello, Velephi; Philip, Neena M; Ehrenkranz, Peter D; Duong, Yen T; Moore, Janet S; Justman, Jessica E

2016-03-01

Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥ 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥ 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥ 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

Use of Third Line Antiretroviral Therapy in Latin America

PubMed Central

Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

2014-01-01

Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931

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.

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

Initiating therapy: when to start, what to use.

PubMed

Hirsch, Martin S

2008-05-15

Decisions regarding whether to start combination antiretroviral therapy (cART) during primary infection and when to initiate treatment during chronic infection continue to evolve. Although current data suggest that there may be a benefit to therapy during primary infection, results are inconclusive. Once begun, treatment probably should be continued indefinitely, since its potential advantages disappear over time if treatment is stopped. Recent studies suggest that cART may be useful at higher CD4 cell count thresholds than are currently recommended in several guidelines. Several regimens are acceptable as initial therapy, with tenofovir/emtricitabine/efavirenz favored by many because of potency and ease of administration. Other favored regimens include combinations of 2 nucleoside (or nucleotide) reverse-transcriptase inhibitors and a ritonavir-boosted protease inhibitor. Some new antiretroviral drugs under study, particularly integrase inhibitors, may prove useful in treatment-naive patients.

[Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

PubMed

Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

2013-01-01

A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection

PubMed Central

Anderson, Christy M.; Var, Susanna R.; Oliveira, Michelli F.; Lada, Steven M.; Vargas, Milenka V.; Little, Susan J.; Richman, Douglas D.; Strain, Matthew C.; Pérez-Santiago, Josué; Smith, Davey M.

2016-01-01

ABSTRACT Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and is associated with increased T-cell activation and HIV disease progression. We hypothesized that the presence of replication of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence HIV DNA decay during antiretroviral therapy (ART). We investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, HIV-infected men who have sex with men, who started ART within a median of 3 months from their estimated date of infection (EDI) and were monitored for a median of 19 months thereafter. Levels of HIV, CMV, and EBV DNA and cellular HIV RNA were measured by droplet digital PCR (ddPCR) for each time point. Using a general linear mixed-effect regression model, we evaluated associations between the presence of detectable CMV DNA and EBV DNA levels and HIV DNA decay and cellular HIV RNA levels, while adjusting for peak HIV RNA, nadir CD4+ count, CD4/CD8 ratio, CMV IgG levels, time from EDI to ART initiation, time from ART initiation to virologic suppression, detectable CMV DNA pre-ART, and age. The presence of intermittent CMV DNA in PBMC during ART was significantly associated with slower decay of HIV DNA (P = 0.011) but not with increased cellular HIV RNA transcription or more detectable 2-long terminal repeat circles. Higher levels of EBV DNA were also associated with higher levels of HIV DNA (P < 0.001) and increased unspliced cellular HIV RNA transcription (P = 0.010). These observations suggest that replication of HHV may help maintain a larger HIV DNA reservoir, but the underlying mechanisms remain unclear. IMPORTANCE Over three-fourths of HIV-infected men have at least one actively replicating human herpesvirus (HHV) in their mucosal secretions at any one time. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the most common, and although it is often asymptomatic, such CMV and EBV

Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.

PubMed

Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A

2015-11-01

There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.

Mortality in the Year Following Antiretroviral Therapy Initiation in HIV-Infected Adults and Children in Uganda and Zimbabwe

PubMed Central

Walker, A. Sarah; Prendergast, Andrew J.; Mugyenyi, Peter; Munderi, Paula; Hakim, James; Kekitiinwa, Addy; Katabira, Elly; Gilks, Charles F.; Kityo, Cissy; Nahirya-Ntege, Patricia; Nathoo, Kusum; Gibb, Diana M.

2012-01-01

Background. Adult mortality in the first 3 months on antiretroviral therapy (ART) is higher in low-income than in high-income countries, with more similar mortality after 6 months. However, the specific patterns of changing risk and causes of death have rarely been investigated in adults, nor compared with children in low-income countries. Methods. We used flexible parametric hazard models to investigate how mortality risks varied over the first year on ART in human immunodeficiency virus–infected adults (aged 18–73 years) and children (aged 4 months to 15 years) in 2 trials in Zimbabwe and Uganda. Results. One hundred seventy-nine of 3316 (5.4%) adults and 39 of 1199 (3.3%) children died; half of adult/pediatric deaths occurred in the first 3 months. Mortality variation over year 1 was similar; at all CD4 counts/CD4%, mortality risk was greatest between days 30 and 50, declined rapidly to day 180, then declined more slowly. One-year mortality after initiating ART with 0–49, 50–99 or ≥100 CD4 cells/μL was 9.4%, 4.5%, and 2.9%, respectively, in adults, and 10.1%, 4.4%, and 1.3%, respectively, in children aged 4–15 years. Mortality in children aged 4 months to 3 years initiating ART in equivalent CD4% strata was also similar (0%–4%: 9.1%; 5%–9%: 4.5%; ≥10%: 2.8%). Only 10 of 179 (6%) adult deaths and 1 of 39 (3%) child deaths were probably medication-related. The most common cause of death was septicemia/meningitis in adults (20%, median 76 days) and children (36%, median 79 days); pneumonia also commonly caused child deaths (28%, median 41 days). Conclusions. Children ≥4 years and adults with low CD4 values have remarkably similar, and high, mortality risks in the first 3 months after ART initiation in low-income countries, similar to cohorts of untreated individuals. Bacterial infections are a major cause of death in both adults and children; targeted interventions could have important benefits. PMID:22972859

Which factors hinder the decision of Polish HIV-positive patients to take up antiretroviral therapy?

PubMed

Rogowska-Szadkowska, D; Chlabicz, S; Oltarzewska, M A; Sawicka-Powierza, J

2009-03-01

The implementation of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced mortality and morbidity for HIV-positive patients worldwide. However not all eligible persons start HAART. To identify reasons for therapy refusal by HIV-positive persons we performed a questionnaire study. The investigation was conducted among 321 HIV-positive individuals and focused on the decision to take up antiretroviral treatment. Out of 71 untreated patients, 34 (47.9%) admitted that in their case the therapy was not indicated, whereas 20 (28.3%) were afraid of potential side effects that might change their appearance, e.g. face lipoatrophy. Only the treated patients had been prepared to take up therapy, although 17 patients (6.0%) had not received any explanation of the therapy principles, aims or necessity to comply with medication regime. The therapy is generally not discussed with the patients for whom it is not currently indicated, which may contribute to the fixation of fears and prejudices. Doctors who treat HIV-positive patients should be aware of the prejudices and fears their patients have towards antiretroviral therapy in order to react properly and by means of the available antiretroviral drugs help prolong life and improve its quality.

Time Preferences Predict Mortality among HIV-Infected Adults Receiving Antiretroviral Therapy in Kenya.

PubMed

Thirumurthy, Harsha; Hayashi, Kami; Linnemayr, Sebastian; Vreeman, Rachel C; Levin, Irwin P; Bangsberg, David R; Brewer, Noel T

2015-01-01

Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals' intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non-HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants' time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence ≥90%. Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence ≥90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding.

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia.

PubMed

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Wasihun, Araya Gebreyesus; Dejene, Tsehaye Asmelash

2018-01-01

Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. The current result shows that immunological and virological failure is a problem in a setting

Incidence and risk factors of fever in a contemporary cohort of HIV-patients with good access to antiretroviral therapy.

PubMed

De Munter, Paul; Derdelinckx, Inge; Peetermans, Willy E; Fieuws, Steffen; Vanderschueren, Steven; Van Wijngaerden, Eric

2017-08-01

To study incidence and to determine risk factors of fever in a contemporary cohort of HIV-infected patients with access to antiretroviral therapy. Prospective study in a cohort of HIV-infected patients in Belgium from 2009 to 2013. 759 patients were followed for a total of 2136 patient years. The incidence of fever was low, with an incidence rate of 0.103 (95% CI 0.078; 0.135) febrile episodes per patient per year for temperature 38.3 °C or higher measured by a health care provider. Gender, age, ethnicity, and calendar year of measurement were no significant risk factors for fever in univariable analysis, but recent HIV diagnosis, prior AIDS, nadir CD4 cell count, last CD4 cell count, and viral load were, as were use of antiretroviral therapy, recent start of antiretroviral therapy and recent switch of antiretroviral therapy. Recent stop of antiretroviral therapy was no significant risk factor. In multivariable analysis prior AIDS, last CD4 and viral load remained significant risk factors, but use of antiretroviral therapy not. In this contemporary cohort, incidence of fever was low but CD4 cell count less than 200/mm³ remained associated with the highest incidence of fever.

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.

PubMed

Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias; May, Margaret; Grabar, Sophie; Furrer, Hansjakob; Sabin, Caroline; Fatkenheuer, Gerd; Justice, Amy; Reiss, Peter; d'Arminio Monforte, Antonella; Gill, John; Hogg, Robert; Bonnet, Fabrice; Kitahata, Mari; Staszewski, Schlomo; Casabona, Jordi; Harris, Ross; Saag, Michael

2009-04-15

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. 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 antiretroviral 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. 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]). In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The

HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries.

PubMed

Bennett, Diane E; Jordan, Michael R; Bertagnolio, Silvia; Hong, Steven Y; Ravasi, Giovanni; McMahon, James H; Saadani, Ahmed; Kelley, Karen F

2012-05-01

The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.

Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

PubMed Central

2014-01-01

Background Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. Methods Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider’s perspective using site- and country-level data and are reported in 2011 USD. Results Patients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293), ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months’ worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site. Conclusions Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were

Cross-sectional comparative study of risky sexual behaviours among HIV-infected persons initiated and waiting to start antiretroviral therapy in rural Rakai, Uganda.

PubMed

Nakiganda, Lydia Jacenta; Nakigozi, Gertrude; Kagaayi, Joseph; Nalugoda, Fred; Serwadda, David; Sewankambo, Nelson; Gray, Ronald; Ndyanabo, Anthony; Muwanika, Richard; Asamoah, Benedict Oppong

2017-09-11

To compare risky sexual behaviours between HIV-positive persons initiated on antiretroviral therapy (ART) (ART-experienced) and persons waiting to start on ART (ART-naive) and assess predictors of risky sexual behaviours among HIV-infected patients in rural Rakai district, Uganda. This is a cross-sectional study that used data from the Rakai Community Cohort Study (RCCS) database between 2013 and 2014. A structured questionnaire was used for data collection. We used stepwise logistic regression as an index to estimate the adjusted ORs for the association between risky sexual behaviours and ART treatment status. This study was conducted in Rakai district, located in south-western Uganda. The data for this study were extracted from the RCCS. RCCS is an open prospective cohort of approximately 15 000 consenting participants aged 15-49 years. HIV-positive participants aged 18-49 years who had sex at least once a month with any partner prior to the start of the study. Inconsistent/no condom use in the last 12 months, alcohol use at last sexual encounter, and two or more sexual partners. ART-naive participants were more likely to report inconsistent condom use (OR=1.74, 95% CI 1.11 to 2.73) and more likely to drink alcohol at last sexual encounter (OR=1.65, 95% CI 1.11 to 2.46), compared with ART-experienced patients. ART treatment status (p<0.001) was a significant predictor of risky sexual behaviours. Both marital status (p=0.016) and occupation level (p=0.009) were positively associated with inconsistent condom use, while sex (p<0.001) correlated with alcohol use at last sexual encounter. ART-naive participants were more likely to exhibit risky sexual behaviours than the ART-experienced participants. The intensity of risk reduction counselling should be increased for HIV-positive persons waiting to start ART but already in HIV care. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No

Oakland Readers. A Book of Life Stories Told by Students in the Second Start Adult Literacy Program. Levels One-Four.

ERIC Educational Resources Information Center

Lamb, Jessica, Ed.

This set of Oakland Readers consists of four books of oral histories edited on four reading levels. Each book contains life stories told by students in the Second Start Adult Literacy Program. The books are intended for use by tutors and adult students/new readers in adult literacy programs. Life stories of eight students appear in each book. In…

Paying for antiretroviral adherence: is it unethical when the patient is an adolescent?

PubMed

Healy, Justin; Hope, Rebecca; Bhabha, Jacqueline; Eyal, Nir

2017-03-01

With the expansion of antiretroviral treatment programmes, many children and adolescents with HIV in sub-Saharan Africa could expect to live healthy lives. Yet adolescents have the highest levels of poor antiretroviral adherence and of loss to follow-up compared with other age groups. This can lead to increased morbidity and mortality, to the development of drug-resistant strains, and to high societal costs. While financial incentives have been extensively used to promote medication adherence among adults, their use among adolescents remains rare. And while there is a large body of ethical literature exploring financial incentives among adults, little philosophical thought has gone into their use among adolescents. This paper explores three oft-mentioned ethical worries about financial incentives for health behaviours and it asks whether these concerns are more serious in the context of incentives for improving adolescent adherence. The three worries are that such incentives would unduly coerce adolescents' decision-making, would compromise distributive justice and would crowd out intrinsic motivations and non-monetary values. Our tentative conclusion is that more empirical investigation of these concerns is necessary, and that at this point they are not compelling enough to rule out trials in which adolescents are incentivised for antiretroviral adherence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Even Start Projects Serving Migrant Families: Resource Guide.

ERIC Educational Resources Information Center

Gonzales, Miriam; Goldstein, David; Stief, Elizabeth; Fiester, Leila; Weiner, Lisa; Waiters, Katrina

Even Start was created by federal legislation to address poverty and illiteracy among low-income families by integrating early childhood education, adult literacy or adult basic education, and parenting education into a unified family literacy program. Migrant Education Even Start (MEES) projects resemble other Even Start projects but are affected…

Special Analysis of Migrant Education Even Start Data. Even Start Information System.

ERIC Educational Resources Information Center

Tao, Fumiyo; Arriola, Christine

This report analyzes data submitted by 11 of 14 state Migrant Education Even Start (MEES) projects operating in 1994-95. These projects provide migrant families with an integrated program of early childhood education, adult education, and parenting education. The data were drawn from the Even Start Information System (ESIS), which collected…

National Evaluation of the Even Start Family Literacy Program. Report on Even Start Projects for Indian Tribes and Tribal Organizations.

ERIC Educational Resources Information Center

Levin, Marjorie; Moss, Marc; Swartz, Janet; Khan, Sherry; Tarr, Hope

The tribal Even Start program is one of the set-aside components of the U.S. Department of Education's Even Start Family Literacy Program. Even Start combines adult literacy, early childhood education, and parenting education services for parents eligible for adult education and their children from birth to age 7. In 1994-95, nine Indian tribes…

Optimizing Research to Speed Up Availability of Pediatric Antiretroviral Drugs and Formulations.

PubMed

Penazzato, Martina; Gnanashanmugam, Devasena; Rojo, Pablo; Lallemant, Marc; Lewis, Linda L; Rocchi, Francesca; Saint Raymond, Agnes; Ford, Nathan; Hazra, Rohan; Giaquinto, Carlo; Belew, Yodit; Gibb, Diana M; Abrams, Elaine J

2017-06-01

Globally 1.8 million children are living with human immunodeficiency virus (HIV), yet only 51% of those eligible actually start treatment. Research and development (R&D) for pediatric antiretrovirals (ARVs) is a lengthy process and lags considerably behind drug development in adults. Providing safe, effective, and well-tolerated drugs for children remains critical to ensuring scale-up globally. We review current approaches to R&D for pediatric ARVs and suggest innovations to enable simplified, faster, and more comprehensive strategies to develop optimal formulations. Several approaches could be adopted, including focusing on a limited number of prioritized formulations and strengthening existing partnerships to ensure that pediatric investigation plans are developed early in the drug development process. Simplified and more efficient mechanisms to undertake R&D need to be put in place, and financing mechanisms must be made more sustainable. Lessons learned from HIV should be shared to support progress in developing pediatric formulations for other diseases, including tuberculosis and viral hepatitis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.

PubMed

Garvey, L; Winston, A; Walsh, J; Post, F; Porter, K; Gazzard, B; Fisher, M; Leen, C; Pillay, D; Hill, T; Johnson, M; Gilson, R; Anderson, J; Easterbrook, P; Bansi, L; Orkin, C; Ainsworth, J; Palfreeman, A; Gompels, M; Phillips, A N; Sabin, C A

2011-02-22

The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

Relationship between medication synchronization and antiretroviral adherence.

PubMed

Ghassemi, Emily; Smith, Jennifer; Owens, Laura; Herring, Charles; Holland, Melissa

2018-06-12

To compare antiretroviral adherence (measured as the proportion of days covered [PDC]) and change in viral load in insured, HIV-infected, adult outpatients enrolled and not enrolled in a medication synchronization program. This was a multicenter, retrospective, pilot cohort study. Fifty-eight insured, HIV-infected, outpatients at least 18 years of age receiving antiretroviral therapy (ART) for at least 3 months as of August 2015 were included. PDC, viral load, PDC dichotomized into adherent or nonadherent, and viral load dichotomized into detectable or undetectable were collected for each patient. Study data were compared in those with (enrolled) and without (not enrolled or control) medication synchronization. The study end points were analyzed between the 2 groups retrospectively after 3 months. PDC in patients undergoing medication synchronization was significantly higher than in control patients: mean ± SD 96 ± 9% versus 71 ± 27%, respectively (P < 0.0001). The medication synchronization group was also more likely to be adherent to ART than the control group (odds ratio 10.67, 95% confidence interval 2.63-43.31). In the medication synchronization group, 75.9% of patients had an undetectable baseline viral load, and 83.3% had an undetectable viral load at study completion. In the control group, 62.1% and 64.7% had an undetectable viral load at baseline and completion, respectively. No statistically significant change in viral load was observed between groups (P = 0.34). In insured, HIV-infected, adult outpatients, implementation of a medication synchronization program was associated with improved ART adherence. Future studies are needed to better assess the impact of medication synchronization on clinical outcomes. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Patient-Reported Symptoms on the Antiretroviral Regimen Efavirenz/Emtricitabine/Tenofovir

PubMed Central

Gordon, Kirsha; Rodriguez-Barradas, Maria C.; Justice, Amy C.

2012-01-01

Abstract Most patients (80–90%) newly diagnosed with HIV are started on the antiretroviral regimen efavirenz, emtricitabine, and tenofovir (EFV/FTC/TDF). Existing studies of patient tolerability, however, are limited. We compared symptom experiences of patients on EFV/FTC/TDF, and the subsequent impact on health-related quality of life, with those of patients on other combination antiretroviral therapy (cART). We conducted a cross-sectional analysis of the Veterans Aging Cohort Study from February 2008 to August 2009 to compare the symptom experiences of patients on EFV/FTC/TDF vs. other cART, unadjusted and then adjusted for treatment characteristics, and comorbid disease severity. We then assessed the association between EFV/FTC/TDF use and health-related quality of life. Among the 1,759 patients in our analytic sample, EFV/FTC/TDF use was associated with fewer symptoms than was other cART. The use of EFV/FTC/TDF was independently associated with health-related quality of life, and this association was at least partially explained by symptom burden. PMID:22612469

[Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

PubMed

Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

2017-08-01

In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to

Low incidence of abacavir hypersensitivity reaction among African children initiating antiretroviral therapy.

PubMed

Nahirya-Ntege, Patricia; Musiime, Victor; Naidoo, Bethany; Bakeera-Kitaka, Sabrina; Nathoo, Kusum; Munderi, Paula; Mugyenyi, Peter; Kekitiinwa, Adeodata; Bwakura-Dangarembizi, Mutsa F; Crawley, Jane

2011-06-01

Hypersensitivity reactions are reported in approximately 5% of adults receiving abacavir, but there are few published data in children. Among 1150 African children receiving antiretroviral therapy in a randomized trial, suspected hypersensitivity reactions to abacavir were rare (0.3%; 95% CI, 0.01-0.9). Patients were managed successfully through the provision of clear guidelines and education of clinical staff, children, and their caregivers.

Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008-2013.

PubMed

Fox, Matthew P; Rosen, Sydney

2015-05-01

We previously published systematic reviews of retention in care after antiretroviral therapy initiation among general adult populations in sub-Saharan Africa. We estimated 36-month retention at 73% for publications from 2007 to 2010. This report extends the review to cover 2008-2013 and expands it to all low- and middle-income countries. We searched PubMed, Embase, Cochrane Register, and ISI Web of Science from January 1, 2008, to December 31, 2013, and abstracts from AIDS and IAS from 2008-2013. We estimated retention across cohorts using simple averages and interpolated missing times through the last time reported. We estimated all-cause attrition (death, loss to follow-up) for patients receiving first-line antiretroviral therapy in routine settings in low- and middle-income countries. We found 123 articles and abstracts reporting retention for 154 patient cohorts and 1,554,773 patients in 42 countries. Overall, 43% of all patients not retained were known to have died. Unweighted averages of reported retention were 78%, 71%, and 69% at 12, 24, and 36 months, after treatment initiation, respectively. We estimated 36-month retention at 65% in Africa, 80% in Asia, and 64% in Latin America and the Caribbean. From lifetable analysis, we estimated retention at 12, 24, 36, 48, and 60 months at 83%, 74%, 68%, 64%, and 60%, respectively. Retention at 36 months on treatment averages 65%-70%. There are several important gaps in the evidence base, which could be filled by further research, especially in terms of geographic coverage and duration of follow-up.

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

PubMed

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

2015-07-01

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

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia

PubMed Central

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Dejene, Tsehaye Asmelash

2018-01-01

Background Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. Methods A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. Result A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. Conclusions The current result shows that immunological and

Factors associated with non-adherence to antiretroviral therapy in adults with AIDS in the first six months of treatment in Salvador, Bahia State, Brazil.

PubMed

Silva, José Adriano Góes; Dourado, Inês; Brito, Ana Maria de; Silva, Carlos Alberto Lima da

2015-06-01

The control of viral replication is essential in the highly active antiretroviral therapy (HAART), and adherence to therapy is instrumental for such control. Individual and external factors influence adhesion to the use of antiretroviral (ARV) drugs. This is a cross-sectional study to investigate factors associated with non-adherence to HAART in AIDS patients in Salvador, Bahia State, Brazil, with age ≥ 13 years and first prescription in 2009. Data was collected from patient charts and pharmacy records. From a total of 216 patients, 65.3% were males; mean age 37.8 ± 9.5 years; single, 67.9%; heterosexual, 64%; more than 8 years of school education, 65.3%; alcohol users, 61.5%; non-smokers, 75,1% or non-illicit drug users, 93.7%. A proportion of 94% started ARV therapy with TCD4+ < 350 cells/mm3; 61.8% were symptomatic; and 68.4% had an adverse drug reaction. The prevalence of non-adherence was 25%. The variables associated were: longer time between HIV infection and AIDS (aOR = 3.9), adverse drug reaction (aOR = 2.4), under 34 years of age (aOR = 2.2), less than 8 years of school education (aOR = 2.2) and illicit drugs use (aOR = 2.6). A high-non-adherence rate is an important problem within the first six months of HAART.

Hypertension among HIV-infected adults receiving highly active antiretroviral therapy (HAART) in Malaysia.

PubMed

Hejazi, Nazisa; Huang, M S L; Lin, Khor Geok; Choong, Lee Christopher Kwok

2013-12-01

There are increasing researches about non-communicable disease such as elevated blood pressure among people living with HIV before and after initiation of highly active antiretroviral therapy (HAART). This cross-sectional study was designed to determine the prevalence of hypertension and associated risk factors among 340 HIV-infected patients on antiretroviral therapy at a Malaysian public hospital providing HIV-related treatment. Data on socioeconomic background, anthropometry, medical history and dietary intake of the patients were collected. Hypertension is defined as blood pressure >=130/85 (mm Hg). Prevalence of hypertension was 45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024-1.078), higher body mass index (OR 1.18, 95%CI 1.106-2.71), bigger waist circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070, 95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95%CI 0.845-2.100) and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were significant risk factors for hypertension (p<0.001). After adjusting for other variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124, p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with hypertension. None of the antiretroviral therapy and immunologic factors was linked to hypertension. In conclusion hypertension among PLHIV was linked to the well-known risk factors such as age, gender and body mass index. With HAART, people can live longer by making monitoring and control of some reversible factors, especially excessive weight gain for maintaining quality of life.

Modeling the impact of early antiretroviral therapy for adults coinfected with HIV and hepatitis B or C in South Africa.

PubMed

Martin, Natasha K; Devine, Angela; Eaton, Jeffrey W; Miners, Alec; Hallett, Timothy B; Foster, Graham R; Dore, Gregory J; Easterbrook, Philippa J; Legood, Rosa; Vickerman, Peter

2014-01-01

There has been discussion about whether individuals coinfected with HIV and hepatitis C virus (HCV) or hepatitis B virus (HBV) (∼30% of all people living with HIV) should be prioritized for early HIV antiretroviral therapy (ART). We assess the relative benefits of providing ART at CD4 count below 500  cells/μl or immediate ART to HCV/HIV or HBV/HIV-coinfected adults compared with HIV-monoinfected adults. We evaluate individual outcomes (HIV/liver disease progression) and preventive benefits in a generalized HIV epidemic setting. We modeled disease progression for HIV-monoinfected, HBV/HIV-coinfected, and HCV/HIV-coinfected adults for differing ART eligibility thresholds (CD4 <350  cells/μl, CD4 <500  cells/μl, immediate ART eligibility upon infection). We report disability-adjusted life-years averted per 100 person-years on ART (DALYaverted/100PYonART) as a measure of the health benefits generated from incremental changes in ART eligibility. Sensitivity analyses explored impact on sexual HIV and vertical HIV, HCV, and HBV transmission. For HBV/HIV-coinfected adults, a switch to ART initiation at CD4 count below 500  cells/μl from CD4 below 350  cells/μl generates 9% greater health benefits per year on ART (48 DALYaverted/100PYonART) than for HIV-monoinfected adults (44 DALYaverted/100PYonART). Additionally, ART at CD4 below 500  cells/μl could prevent 25% and 32% of vertical transmissions of HIV and HBV, respectively. For HCV/HIV-coinfected adults, ART at CD4 below 500  cells/μl generates 10% fewer health benefits (40 DALYaverted/100PYonART) than for HIV monoinfection, unless ART reduces progression to cirrhosis by more than 70% (33% in base-case). The additional therapeutic benefits of ART for HBV-related liver disease results in ART generating more health benefits among HBV/HIV-coinfected adults than HIV-monoinfected individuals, whereas less health benefits are generated amongst HCV/HIV coinfection in a generalized HIV epidemic

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD).

PubMed

Jung, In Young; Boettiger, David; Wong, Wing Wai; Lee, Man Po; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Avihingsanon, Anchalee; Tanuma, Junko; Kumarasamy, Nagalingeswaran; Kamarulzaman, Adeeba; Zhang, Fujie; Kantipong, Pacharee; Ng, Oon Tek; Sim, Benedict Lim Heng; Law, Matthew; Ross, Jeremy; Choi, Jun Yong

2017-12-01

Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is

Calculating the affordability of antiretrovirals in St Lucia.

PubMed

Reddock, J R; Grignon, M

2013-01-01

The cost of antiretrovirals is borne by donors in many low- and middle-income countries, including St Lucia. Although donor involvement has facilitated access to antiretrovirals, donor engagement in HIV/AIDS has changed over the years. This paper assesses the affordability of antiretrovirals at the individual level if donors were no longer available to fund the cost of first and second-line antiretrovirals and a prospective third-line regimen. Various conceptions of affordability are reviewed using different assumptions of what is required to maintain a standard of living that would avoid individuals descending into poverty as a result of antiretroviral purchases. These concepts of affordability are operationalized using data from the Household Budgeting Survey conducted in St Lucia in 2005/2006. While there is a range of results for the affordability of first and second-line antiretrovirals depending on which standard of affordability is used, third-line antiretrovirals are unaffordable to more than 80% of the population across the four standards of affordability used - the national poverty line, 50% of median annual consumption, 10% of annual consumption and a proposed reasonable minimum standard.

The importance of the patient-clinician relationship in adherence to antiretroviral medication.

PubMed

Molassiotis, Alex; Morris, Kate; Trueman, Ian

2007-12-01

The aim of the study was to assess dimensions of the patient-clinician relationship in relation to adherence with antiretroviral medication in a sample of HIV patients. This was a correlational evaluation, using a cross-sectional design. Thirty-eight HIV patients in two UK HIV units provided complete data. Analysis suggested that the elements of the patient-clinician relationship contributing to adherence with medication were the patient perception of being valued and respected by the clinician, the patients' ability to initiate discussions about the treatment, empowerment and level of trust placed in the nurse. The latter, and the time since starting antiretroviral treatment, were the only two variables that could predict adherence in a regression model, explaining 41% of the variance in adherence. Building trusted relationships with the patients and investing in educational and communication techniques to improve the therapeutic relationship could strongly contribute to HIV patients to maintaining high adherence rates.

Washington State Even Start 1993-1994: Final Evaluation. A Report to the Office of Adult Literacy.

ERIC Educational Resources Information Center

Iglitzin, Lynne; Wandschneider, Mary

All 18 Washington State Even Start sites participated in the program's evaluation. Site coordinators administered the assessment and evaluation measures to the adults served by the program and to teachers working with children at both entry and exit from the program. An indepth study was conducted of 134 families for whom there were complete sets…

[Budget impact analysis of antiretroviral therapy. A reflection based on the GESIDA guidelines].

PubMed

2012-01-01

The latest version of the Spanish clinical practice guidelines on antiretroviral therapy (ART) in HIV-infected adults, developed by the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan, recommends initiating ART early in certain circumstances. The aim of this study was to estimate the budget impact of this recommendation by using the data from the VACH cohort. We considered a scenario in which all naïve asymptomatic patients would initiate ART if they had <500 lymphocytes, or a CD4/μL count >500/μL if they were older than 55 years, or had high viral load, liver disease, chronic kidney disease or high cardiovascular risk. The study was designed as a cost analysis in terms of annual pharmaceutical expenditure. The only costs included were those relating to the ART combinations analyzed. To estimate these costs, we assumed that this guideline had a penetration of 80%, an adherence of 95% and 12% dropouts. A total of 12,500 patients were reviewed. Of these, 1,127 (10%) had not initiated ART; CD4 lymphocyte count was 350-500 in 294 (26.1%) and > 500 in 685 (60.8%). If the new clinical practice guideline were applied, 45.2% of naïve patients (95% CI: 42.4%-48.2%) would be advised to start ART. Carrying out this recommendation in hospitals of the VACH cohort would require an additional annual investment of € 3,270,975 and would increase the overall cost of antiretroviral drugs by 3%. In the framework of health economics, incorporating economic impact estimates - such as those performed in this study - into clinical practice guidelines would be advisable to increase their feasibility. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000-2012.

PubMed

Wall, Emma C; Everett, Dean B; Mukaka, Mavuto; Bar-Zeev, Naor; Feasey, Nicholas; Jahn, Andreas; Moore, Mike; van Oosterhout, Joep J; Pensalo, Paul; Baguimira, Kenneth; Gordon, Stephen B; Molyneux, Elizabeth M; Carrol, Enitan D; French, Neil; Molyneux, Malcolm E; Heyderman, Robert S

2014-05-01

We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART). We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012. There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio [IRR], 0.93; 95% CI, .92-.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85-.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97-1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100,000 cases in children aged <14 years, 6 per 100,000 adolescents, and 10 per 100,000 adults. Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic "meningitis belt" in Africa is essential.

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

PubMed Central

2011-01-01

Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral

Examining the production costs of antiretroviral drugs.

PubMed

Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

2006-08-22

To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

PubMed Central

Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

2011-01-01

Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

Antiretroviral drug treatment of CNS HIV-1 infection.

PubMed

Yilmaz, Aylin; Price, Richard W; Gisslén, Magnus

2012-02-01

The advent of combination antiretroviral treatment has had a profound impact on CNS HIV infection and its clinical complications, but neurological impairment still occurs in patients on systemically effective combination therapy, and in some patients it may be important to consider antiretroviral drug entry and effects within the CNS. There are now data on the CNS exposure for most antiretroviral drugs. This review focuses on the CNS pharmacokinetics and pharmacodynamics of antiretroviral drugs in humans, and also discusses controversies in this field.

The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

PubMed

Krentz, Hartmut B; Gill, M John

2016-01-01

Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

Insurability of HIV-positive people treated with antiretroviral therapy in Europe: collaborative analysis of HIV cohort studies

PubMed Central

Kaulich-Bartz, Josee; Dam, Wayne; May, Margaret T.; Lederberger, Bruno; Widmer, Urs; Phillips, Andrew N.; Grabar, Sophie; Mocroft, Amanda; Vilaro, Josep; van Sighem, Ard; Moreno, Santiago; Dabis, François; Monforte, Antonella D’Arminio; Teira, Ramon; Ingle, Suzanne M.; Sterne, Jonathan A.C.

2013-01-01

Objective: To increase equitable access to life insurance for HIV-positive individuals by identifying subgroups with lower relative mortality. Design: Collaborative analysis of cohort studies. Methods: We estimated relative mortality from 6 months after starting antiretroviral therapy (ART), compared with the insured population in each country, among adult patients from European cohorts participating in the ART Cohort Collaboration (ART-CC) who were not infected via injection drug use, had not tested positive for hepatitis C, and started triple ART between 1996–2008. We used Poisson models for mortality, with the expected number of deaths according to age, sex and country specified as offset. Results: There were 1236 deaths recorded among 34 680 patients followed for 174 906 person-years. Relative mortality was lower in patients with higher CD4 cell count and lower HIV-1 RNA 6 months after starting ART, without prior AIDS, who were older, and who started ART after 2000. Compared with insured HIV-negative lives, estimated relative mortality of patients aged 20–39 from France, Italy, United Kingdom, Spain and Switzerland, who started ART after 2000 had 6-month CD4 cell count at least 350 cells/μl and HIV-1 RNA less than104 copies/ml and without prior AIDS was 459%. The proportion of exposure time with relative mortality below 300, 400, 500 and 600% was 28, 43, 61 and 64%, respectively, suggesting that more than 50% of patients (those with lower relative mortality) could be insurable. Conclusion: The continuing long-term effectiveness of ART implies that life insurance with sufficiently long duration to cover a mortgage is feasible for many HIV-positive people successfully treated with ART for more than 6 months. PMID:23449349

A Mobile Gaming Intervention to Increase Adherence to Antiretroviral Treatment for Youth Living With HIV: Development Guided by the Information, Motivation, and Behavioral Skills Model.

PubMed

Whiteley, Laura; Brown, Larry; Lally, Michelle; Heck, Nicholas; van den Berg, Jacob J

2018-04-23

Highly active combination antiretroviral treatment has been shown to markedly improve the health of HIV-infected adolescents and young adults. Adherence to antiretroviral treatment leads to decreased morbidity and mortality and decreases the number of hospitalizations. However, these clinical achievements can only occur when young persons with HIV are adherent to care. Unfortunately, adolescents and young adults have poorer rates of adherence to antiretroviral medications and poorer rates of retention in care than older adults. Novel and engaging digital approaches are needed to help adolescents and young adults living with HIV be adherent to treatment. The aim of this study was to develop an immersive, action-oriented iPhone gaming intervention to improve adherence to antiretroviral medication and treatment. Game development was guided by social learning theory, taking into consideration the perspectives of adolescents and young adults living with HIV. A total of 20 adolescents and young adults were recruited from an HIV care clinic in Rhode Island, and they participated in qualitative interviews guided by the information-motivation-behavioral skills model of behavior change. The mean age of participants was 22 years, 60% (12/20) of the participants identified as male, and 60% (12/20) of the sample reported missing a dose of antiretroviral medication in the previous week. Acceptability of the game was assessed with client service questionnaire and session evaluation form. A number of themes emerged that informed game development. Adolescents and young adults living with HIV desired informational game content that included new and comprehensive details about HIV, details about HIV as it relates to doctors' visits, and general health information. Motivational themes that emerged were the desire for enhancement of future orientation; reinforcement of positive influences from partners, parents, and friends; collaboration with health care providers; decreasing stigma

A Mobile Gaming Intervention to Increase Adherence to Antiretroviral Treatment for Youth Living With HIV: Development Guided by the Information, Motivation, and Behavioral Skills Model

PubMed Central

2018-01-01

Background Highly active combination antiretroviral treatment has been shown to markedly improve the health of HIV-infected adolescents and young adults. Adherence to antiretroviral treatment leads to decreased morbidity and mortality and decreases the number of hospitalizations. However, these clinical achievements can only occur when young persons with HIV are adherent to care. Unfortunately, adolescents and young adults have poorer rates of adherence to antiretroviral medications and poorer rates of retention in care than older adults. Novel and engaging digital approaches are needed to help adolescents and young adults living with HIV be adherent to treatment. Objective The aim of this study was to develop an immersive, action-oriented iPhone gaming intervention to improve adherence to antiretroviral medication and treatment. Methods Game development was guided by social learning theory, taking into consideration the perspectives of adolescents and young adults living with HIV. A total of 20 adolescents and young adults were recruited from an HIV care clinic in Rhode Island, and they participated in qualitative interviews guided by the information-motivation-behavioral skills model of behavior change. The mean age of participants was 22 years, 60% (12/20) of the participants identified as male, and 60% (12/20) of the sample reported missing a dose of antiretroviral medication in the previous week. Acceptability of the game was assessed with client service questionnaire and session evaluation form. Results A number of themes emerged that informed game development. Adolescents and young adults living with HIV desired informational game content that included new and comprehensive details about HIV, details about HIV as it relates to doctors’ visits, and general health information. Motivational themes that emerged were the desire for enhancement of future orientation; reinforcement of positive influences from partners, parents, and friends; collaboration with

[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.

A randomized trial comparing concise and standard consent forms in the START trial

PubMed Central

Touloumi, Giota; Walker, A. Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G.; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

2017-01-01

Background Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. Methods We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). Results 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. Conclusions An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Trial registration Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008

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

Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy

PubMed Central

Stein, James H.; Komarow, Lauren; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Parker, Robert A.; Torriani, Francesca J.

2008-01-01

Background Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. Objective To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. Methods This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. Results Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (pKW<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (pKW=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. Conclusions Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir. PMID:19956354

Intellectual property rights, market competition and access to affordable antiretrovirals.

PubMed

Pascual, Fernando

2014-01-01

The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.

Start Young!

ERIC Educational Resources Information Center

Rubin, Penni

2002-01-01

Discusses the importance of early interest in science and how effective it is on career choice in adult stages of life. Recommends starting mathematics and science activities in preschool and kindergarten. Describes how to create a career-oriented learning center in the classroom with examples of kitchen chemistry, nutrition/botany, zoology,…

Where are we now? A multicountry qualitative study to explore access to pre-antiretroviral care services: a precursor to antiretroviral therapy initiation

PubMed Central

Bukenya, Dominic; Wringe, Alison; Skovdal, Morten; Ssekubugu, Robert; Paparini, Sara; McLean, Estelle; Bonnington, Oliver; Wamoyi, Joyce; Seeley, Janet

2017-01-01

Objective To explore barriers and facilitators to accessing postdiagnosis HIV care in five sub-Saharan African countries. Methods In-depth interviews were conducted with 77 people living with HIV (PLHIV) in pre-antiretroviral therapy care or not-yet-in care and 46 healthcare workers. Participants were purposely selected from health and demographic surveillance sites in Karonga (Malawi), Manicaland (Zimbabwe), uMkhanyakude (South Africa), Kisesa (Tanzania) and Rakai and Kyamulibwa (Uganda). Thematic content analysis was conducted, guided by the constructs of affordability, availability and acceptability of care.- Results Affordability: Transport and treatment costs were a barrier to HIV care, although some participants travelled to distant clinics to avoid being seen by people who knew them or for specific services. Broken equipment and drug stock-outs in local clinics could also necessitate travel to other facilities. Availability: Some facilities did not offer full HIV care, or only offered all services intermittently. PLHIV who frequently travelled complained that care was seldom available to them in places they visited. Acceptability: Severe pain or sickness was a key driver for accessing postdiagnosis care, whereas asymptomatic PLHIV often delayed care-seeking. A belief in witchcraft was a deterrent to accessing clinical care following diagnosis. Changing antiretroviral therapy guidelines generated uncertainty among PLHIV about when to start treatment and delayed postdiagnosis care. PLHIV reported that healthcare workers’ knowledge, attitudes and behaviours, and their ability to impart health education, also influenced whether they accessed HIV care. Conclusion Despite efforts to decentralise services over the past decade, many barriers to accessing HIV care persist. There is a need to increase sustained access to care for PLHIV not yet on treatment, with initiatives that encompass biomedical aspects of care alongside considerations for individual and

Overcoming Barriers to HIV Treatment Adherence: A Brief Cognitive Behavioral Intervention for HIV-Positive Adults on Antiretroviral Treatment

PubMed Central

Olem, David; Sharp, Kelly M.; Taylor, Jonelle M.; Johnson, Mallory O.

2014-01-01

Maximizing HIV treatment adherence is critical in efforts to optimize health outcomes and to prevent further HIV transmission. The Balance Project intervention uses cognitive behavioral approaches to improve antiretroviral medication adherence through promoting adaptive coping with medication side effect and distress related to HIV. This 5-session intervention has been documented to prevent nonadherence among persons living with HIV who experience high levels of distress associated with their antiretroviral medication side effects. We describe the theoretical underpinnings of the intervention, provide details of the training and session protocols with a case example, and discuss implications for future applications of the intervention in both research and clinical settings. PMID:24855332

Antiretroviral therapy in children: recent advances.

PubMed

Lodha, Rakesh; Manglani, Mamta

2012-12-01

Availability and successful use of various antiretroviral drugs has transformed HIV/AIDS from an incurable to a treatable chronic condition. The antiretroviral therapy can successfully suppress viral replication and preserve the immune system for many years. The implementation of antiretroviral therapy program in resource limited settings using the 'public health approach' of the World Health Organization has had a dramatic impact on the lives of millions of HIV infected individuals. Antiretroviral therapy (ART) in children has many challenges: use of appropriate formulations, regular need for modification of doses as the child grows, adherence issues, etc. To reduce the high morbidity and mortality in HIV infected children, it is currently recommended that all HIV infected children less than 24 mo should receive ART; in older children the indications are based on clinical and/or immunological criteria. Highly active antiretroviral therapy regimens include at least 3 antiretroviral drugs. The first line therapy recommended for children is a combination of two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor. Infants who have had exposure to nevirapine should receive a combination of two nucleoside reverse transcriptase inhibitors and a protease inhibitor; the protease inhibitor of choice is ritonavir boosted lopinavir. The success of therapy is dependent on >95 % adherence. The second line regimen, used when the first line therapy fails, is based on a protease inhibitor. The ongoing research focuses on simplification of regimen, discovery of more potent drugs, availability of more pediatric formulations, treatment of drug resistant strains etc. The optimal indications for initiation of therapy in children, are also being studied.

National Evaluation of the Even Start Family Literacy Program: Report on Migrant Even Start Projects.

ERIC Educational Resources Information Center

Levin, Marjorie; Gamse, Beth; Swartz, Janet; Tao, Fumiyo; Tarr, Hope

In fall 1994, 14 state Migrant Education Programs were receiving direct federal grants to administer Migrant Even Start projects. These projects provide migrant families with an integrated program of early childhood education, adult education, and parenting education. As part of the national evaluation of the Even Start Family Literacy Program,…

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

PubMed Central

Celum, Connie; Baeten, Jared

2012-01-01

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

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

PubMed

Baum, Marianna K; Campa, Adriana; Lai, Shenghan; Sales Martinez, Sabrina; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2013-11-27

Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or

Barriers to starting ART and how they can be overcome: individual and operational factors associated with early and late start of treatment.

PubMed

Parkes-Ratanshi, Rosalind; Bufumbo, Leonard; Nyanzi-Wakholi, Barbara; Levin, Jonathan; Grosskurth, Heiner; Lalloo, David G; Kamali, Anatoli

2010-11-01

Despite expanding access to antiretroviral therapy (ART) in Sub-Saharan Africa, there are few data on patients' perceptions about starting ART to explore issues affecting decisions to start ART in eligible individuals during the ART roll out. We studied patterns of ART uptake for 957 participants in a trial of cryptococcal disease prevention and performed a qualitative cross-sectional study about issues affecting decisions to start ART in this cohort. In-depth interviews (IDIs) were conducted with 48 participants who started ART after variable time on the trial. Time to starting ART from trial enrolment decreased during the ART roll out (Median 83 days to 68 days). Multiple factors causing delay to ART were reported; awaiting home visit by service provider (P=0.025), domestic issues (P=0.028), moving from area (P≤0.001) and fear of side effects (P=0.013) were statistically significant. In the IDIs, fear of side effects was the strongest factor for delay and observation of health improvement in others on ART was the strongest inducement to start. Information from patients already taking ART was the most valued source of information. This study provided novel information about factors encouraging people to start ART early; positive beliefs about ART were the most important. Whilst side effects of ART must not be downplayed, programmes should provide information in a balanced way to prevent unnecessary fear of starting ART. Those already receiving ART were found to be good advocates and should be utilised by ART programmes to educate others. © 2010 Blackwell Publishing Ltd.

Survival and determinants of mortality in adult HIV/Aids patients initiating antiretroviral therapy in Somali Region, Eastern Ethiopia

PubMed Central

Damtew, Bereket; Mengistie, Bezatu; Alemayehu, Tadesse

2015-01-01

Introduction Studies have shown high initial mortality in Antiretroviral Therapy (ART) programs from resource-limited settings. However, there is dearth of evidence on treatment outcomes and associated determinant factors in public hospitals. Therefore, the objective of this study is to assess survival and identify predictors of death in adult HIV-infected patients initiating ART at a public hospital in Eastern Ethiopia. Methods A retrospective cohort study was conducted by reviewing baseline and follow-up records of patients who started ART between December 1, 2007 and December 31, 2011 at Kharamara hospital. Time to death was the main outcome measure. Kaplan-Meier models were used to estimate mortality and Cox proportional hazards models to identify predictors of mortality. Results A total of 784 patients (58.4% females) were followed for a median of 60 months. There were 87 (11.1%) deaths yielding an overall mortality rate of 5.15/100 PYO (95% CI: 4.73-6.37). The estimated mortality was 8.4%, 9.8%, 11.3%, 12.7% and 14.1% at 6, 12, 24, 36 and 48 months respectively. The independent predictors of death were single marital status (AHR: 2.31; 95%CI: 1.18-4.50), a bedridden functional status (AHR: 5.91; 95%CI: 2.87-12.16), advanced WHO stage (AHR: 7.36; 95%CI: 3.17-17.12), BMI < 18.5 Kg/m2 (AHR: 2.20; 95%CI: 1.18-4.09), CD4 count < 50 cells/µL (AHR: 2.70; 95%CI: 1.26-5.80), severe anemia (AHR: 4.57; 95%CI: 2.30-9.10), and TB co-infection (AHR: 2.30; 95%CI: 1.28-4.11). Conclusion Improved survival was observed in patients taking ART in Somali region of Ethiopia. The risk for death was higher in patients with advanced WHO stage, low CD4 count, low Hgb, low BMI, and concomitant TB infection. Intensive case management is recommended for patients with the prognostic factors. Optimal immunologic and weight recoveries in the first 6 months suggest increased effort to retain patients in care at this period. PMID:26889319

Sexual behavior and HIV transmission risk of Ugandan adults taking antiretroviral therapy: 3 year follow-up.

PubMed

Apondi, Rose; Bunnell, Rebecca; Ekwaru, John Paul; Moore, David; Bechange, Stevens; Khana, Kenneth; King, Rachel; Campbell, James; Tappero, Jordan; Mermin, Jonathan

2011-06-19

Long-term impact of antiretroviral therapy (ART) on sexual HIV-transmission risk in Africa is unknown. We assessed sexual behavior changes and estimated HIV transmission from HIV-infected adults on ART in Uganda. Between 2003 and 2007, we enrolled and followed ART-naive HIV-infected adults in a home-based AIDS program with annual counseling and testing for cohabitating partners, participant transmission risk-reduction plans, condom distribution and prevention support for cohabitating discordant couples. We assessed participants' HIV plasma viral load and partner-specific sexual behaviors. We defined risky sex as intercourse with inconsistent/no condom use with HIV-negative or unknown serostatus partners in previous 3 months. We compared rates using Poisson regression models, estimated transmission risk using established viral load-specific transmission estimates, and documented sero-conversion rates among HIV-discordant couples. Of 928 participants, 755 (81%) had 36 months data: 94 (10%) died and 79 (9%) missing data. Sexual activity increased from 28% (baseline) to 41% [36 months (P < 0.001)]. Of sexually active participants, 22% reported risky sex at baseline, 8% at 6 months (P < 0.001), and 14% at 36 months (P = 0.018). Median viral load among those reporting risky sex was 122,500 [interquartile range (IQR) 45 100-353 000] copies/ml pre-ART at baseline and undetectable at follow-up. One sero-conversion occurred among 62 cohabitating sero-discordant partners (0.5 sero-conversions/100 person-years). At 36 months, consistent condom use was 74% with discordant partners, 55% with unknown and 46% with concordant partners. Estimated HIV transmission risk reduced 91%, from 47.3 to 4.2/1000 person-years. Despite increased sexual activity among HIV-infected Ugandans over 3 years on ART, risky sex and estimated risk of HIV transmission remained lower than baseline levels. Integrated prevention programs could reduce HIV transmission in Africa.

Coagulation Imbalance and Neurocognitive Functioning in Older HIV+ Adults on Suppressive Antiretroviral Therapy

PubMed Central

Montoya, Jessica l.; Iudicello, Jennifer; Oppenheim, Hannah A.; Fazeli, Pariya l.; Potter, Michael; MA, Qing; Mills, Paul J.; Ellis, Ronald J.; Grant, Igor; Letendre, Scott l.; Moore, David J.

2017-01-01

Objectives To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. Design Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. Methods Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor, and von Willebrand factor), anticoagulation (antithrombin, protein C, and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1, and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning. Results Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4+ cell count was 654 cells/mm3. Levels of soluble biomarkers of procoagulation, anticoagulation, and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. Conclusions Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the etiology of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy

Medication possession ratio predicts antiretroviral regimens persistence in Peru.

PubMed

Salinas, Jorge L; Alave, Jorge L; Westfall, Andrew O; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H

2013-01-01

In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

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

PubMed

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

2006-01-01

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

Effect of cotrimoxazole prophylaxis on malaria occurrence among HIV-infected adults in West Africa: the MALHIV Study.

PubMed

Eholié, Serge P; Ello, Frédéric N; Coffie, Patrick A; Héma, Arsène; Minta, Daouda K; Sawadogo, Adrien

2017-09-01

Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm 3 according to 2006 WHO guidelines. We assessed the impact of CTX prophylaxis on the risk of malaria episodes in HIV-1-infected adults from four West African countries with different patterns of malaria transmission. Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm 3 or were at WHO clinical stage ≥2. For patients who did not start CTX at enrolment (non-CTX group) and started CTX afterwards, follow-up was censored at CTX initiation. We used Cox's proportional hazard model to compare the risk of malaria between CTX groups. A total of 514 participants (median CD4 count 238 cells/mm 3 ) were followed for a median of 15 months. At enrolment, 347 started CTX, and 261 started ART. During the follow-up, 28 started CTX. The incidence of malaria was 8.7/100 PY (95%CI 6.3-11.5) overall, 5.2/100 PY (95%CI 3.1-8.3) in the CTX group and 15.5/100 PY (95%CI 10.3-22.1) in the non-CTX group. In multivariate analysis, CTX led to a 69% reduction in the risk of malaria (aHR 0.31, 95%CI 0.10-0.90). Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region. © 2017 John Wiley & Sons Ltd.

Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.

PubMed

Tanuma, Junko; Matsumoto, Shoko; Haneuse, Sebastien; Cuong, Do Duy; Vu, Tuong Van; Thuy, Pham Thi Thanh; Dung, Nguyen Thi; Dung, Nguyen Thi Hoai; Trung, Nguyen Vu; Kinh, Nguyen Van; Oka, Shinichi

2017-12-01

Achieving viral suppression is key in the global strategy to end the HIV epidemic. However, the levels of viral suppression have yet to be described in many resource-limited settings. We investigated the time to virologic failure (VF; defined as a viral load of ≥1000 copies/ml) and changes in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired early immune recovery (defined as not attaining an increase in 100 cells/mm 3 in CD4 counts at 24 months) were further analysed. From 1806 participants, 225 were identified as having VF at a median of 50 months of first-line ART. The viral suppression rate at 12 months was 95.5% and survival without VF was maintained above 90% until 42 months. An increase in CD4 counts from the baseline was greater in groups with lower baseline CD4 counts. A younger age (multivariate hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR 1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT)) were associated with earlier VF. Factors associated with impaired early immune recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. Durable high-rate viral suppression was observed in the cohort of patients on first-line ART in Vietnam. Our results highlight the need to increase adherence support among injection drug users and HCV co-infected patients. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Bacterial Meningitis in Malawian Adults, Adolescents, and Children During the Era of Antiretroviral Scale-up and Haemophilus influenzae Type b Vaccination, 2000–2012

PubMed Central

Wall, Emma C.; Everett, Dean B.; Mukaka, Mavuto; Bar-Zeev, Naor; Feasey, Nicholas; Jahn, Andreas; Moore, Mike; van Oosterhout, Joep J.; Pensalo, Paul; Baguimira, Kenneth; Gordon, Stephen B.; Molyneux, Elizabeth M.; Carrol, Enitan D.; French, Neil; Molyneux, Malcolm E.; Heyderman, Robert S.

2014-01-01

Background. We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART). Methods. We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012. Results. There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio [IRR], 0.93; 95% CI, .92–.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85–.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97–1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100 000 cases in children aged <14 years, 6 per 100 000 adolescents, and 10 per 100 000 adults. Conclusions. Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic “meningitis belt” in Africa is essential. PMID:24496208

The clinical epidemiology of young adults starting renal replacement therapy in the UK: presentation, management and survival using 15 years of UK Renal Registry data

PubMed Central

Hamilton, Alexander J; Casula, Anna; Ben-Shlomo, Yoav; Caskey, Fergus J; Inward, Carol D

2018-01-01

Abstract Background Clinical epidemiology data for young adults on renal replacement therapy (RRT) are lacking. While mostly transplanted, they have an increased risk of graft loss during young adulthood. Methods We combined the UK Renal Registry paediatric and adult databases to describe patient characteristics, transplantation and survival for young adults. We grouped patients 11–30 years of age starting RRT from 1999 to 2008 by age band and examined their course during 5 years of follow-up. Results The cohort (n = 3370) was 58% male, 79% white and 29% had glomerulonephritis. Half (52%) started RRT on haemodialysis (HD). Most (78%) were transplanted (18% pre-emptive, 61% as second modality); 11% were not listed for transplant. Transplant timing varied by age group. The deceased:living donor kidney transplant ratio was 2:1 for 11–<16 year olds and 1:1 otherwise. Median deceased donor transplant waiting times ranged from 6 months if <16 years of age to 17 months if ≥21 years. Overall 8% died, with being on dialysis and not transplant listed versus transplanted {hazard ratio [HR] 16.6 [95% confidence interval (CI) 10.8–25.4], P < 0.0001} and diabetes versus glomerulonephritis [HR 4.03 (95% CI 2.71–6.01), P < 0.0001] increasing mortality risk. Conclusions This study highlights the frequent use of HD and the importance of transplant listing and diabetes for young adults. More than half the young adults in our cohort started renal replacement therapy on HD. One in 10 young adults were not listed for transplant by 5 years and were ∼20 times more likely to die than those who were transplanted. Diabetes as a primary renal disease was common among young adults and associated with increased mortality. Overall, almost 1 in 10 young adults had died by 5 years from the start of RRT. PMID:28339838

Long-Acting Antiretrovirals: Where Are We now?

PubMed

Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

2017-04-01

Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

Effects of highly active antiretroviral therapy on the survival of HIV-infected adult patients in urban slums of Kenya

PubMed Central

Muhula, Samuel Opondo; Peter, Memiah; Sibhatu, Biadgilign; Meshack, Ndirangu; Lennie, Kyomuhangi

2015-01-01

Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated with mortality among adult patients on ART in resource poor, urban, sub-Saharan African setting. A prospective open cohort study was conducted with adult patients on ART at a clinic in Kibera slums, Nairobi, Kenya. The patients’ enrollment to care was between March 2005 and November 2011. Descriptive statistics were computed and Kaplan-Meier (KM) methods used to estimate survival time while Cox's proportional hazards (CPH) model fitted to determine mortality predictors. A total of 2,011 adult patients were studied, 69% being female. Female gender (p = 0.0016), zidovudine-based regimen patients (p < 0.0001), CD4 count >351 patients (p < 0.0001), WHO stage I patients (p < 0.0001) and “Working” functional status patients recorded better survival probability on ART. In CPH analysis, the hazard of dying was higher in patients on Stavudine-based regimen(hazard ratio (HR) =1.8; 95% CI, 1.5-2.2; p < 0.0001),CD4 count <50 cells/µl (HR = 1.6; 95% CI, 1.5-1.7;p < 0.0001), WHO Stage IV at ART initiation (HR = 1.3; 95% CI, 1.1-1.6; p = 0.016) and bedridden patients (HR = 2.7; 95% CI, 1.7-4.4;p < 0.0001). There was increased mortality among the males, those with advanced Immunosuppression, late WHO stage and bedridden patients. The findings further justify the need to switch patients on Stavudine-based regimen as per the WHO recommendations. PMID:26090021

[Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

PubMed

Fukutake, Katsuyuki

2015-11-01

Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review].

Dosing antiretroviral medication when crossing time zones: a review

PubMed Central

Lewis, Joseph M.; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

2016-01-01

International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID:26684823

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

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

2015-01-01

Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

PubMed Central

Koenig, Serena P.; Bang, Heejung; Severe, Patrice; Jean Juste, Marc Antoine; Ambroise, Alex; Edwards, Alison; Hippolyte, Jessica; Fitzgerald, Daniel W.; McGreevy, Jolion; Riviere, Cynthia; Marcelin, Serge; Secours, Rode; Johnson, Warren D.; Pape, Jean W.; Schackman, Bruce R.

2011-01-01

Background In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. Methods and Findings Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS). Conclusions Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests. Trial registration ClinicalTrials.gov NCT00120510 Please see

The effects of HIV self-testing on the uptake of HIV testing and linkage to antiretroviral treatment among adults in Africa: a systematic review protocol.

PubMed

Njau, Bernard; Damian, Damian J; Abdullahi, Leila; Boulle, Andrew; Mathews, Catherine

2016-04-05

HIV is still a global public health problem. More than 75 % of HIV-infected people are in Africa, and most of them are unaware of their HIV status, which is a barrier to accessing antiretroviral treatment. Our review aims, firstly, to determine whether HIV self-testing is an effective method to increase the uptake of testing, the yield of new HIV-positive diagnoses, and the linkage to antiretroviral treatment. Secondly, we aim to review the factors that facilitate or impede the uptake of HIV self-testing. Participants will be adults living in Africa. For the first aim, the intervention will be HIV self-testing either alone or in addition to HIV testing standard of care. The comparison will be HIV testing standard of care. The primary outcomes will be (i) uptake of HIV testing and (ii) yield of new HIV-positive diagnoses. The secondary outcomes will be (a) linkage to antiretroviral (ARV) treatment and (b) incidence of social harms. For the second aim, we will review barriers and facilitators to the uptake of self-testing. We will search PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide, and CINAHL for eligible studies from 1998, with no language limits. We will check reference lists of included studies for other eligible reports. Eligible studies will include experimental and observational studies. Two authors will independently screen the search output, select studies, and extract data, resolving discrepancies by consensus and discussion. Two authors will use Cochrane risk of bias tools for experimental studies, the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Critical Appraisal Skills Programme (CASP) quality assessment tool for qualitative studies. Innovative and cost-effective community-based HIV testing strategies, such as self-testing, will contribute to universal coverage of HIV testing in Africa. The findings from this systematic review will guide development of self

An overview of the antiretroviral market.

PubMed

Camponeschi, Geannan; Fast, Jessica; Gauval, Marianne; Guerra, Katherine; Moore, Meredith; Ravinutala, Siddharth; Ripin, David; Shepel, Vadim

2013-11-01

An understanding of the current state of the antiretroviral marketplace is an important context in which to consider drug optimization work. The antiretroviral marketplace has undergone a remarkable evolution over the past 11 years, expanding from serving less than 300 000 patients in low and middle-income countries in 2002 to almost 10 million patients today. In addition to dramatic growth, a steady and rapid improvement in the drugs and drug regimens used to treat patients has characterized a rapidly changing market. The antiretroviral marketplace has been characterized by rapid growth and a succession of improving drugs and regimens over the past 11 years. The dynamic and innovative marketplace provides a strong platform from which to introduce new, optimized drugs and regimens to better serve patients' health needs.

Stigma and Discrimination faced by HIV-infected Adults on Antiretroviral Therapy for more than 1 Year in Raichur Taluk, Karnataka, India.

PubMed

Muralidharan, Shrikanth; Acharya, Arun Kumar; Margabandu, Shanthi; Purushotaman, Shalini; Kannan, Ranjit; Mahendrakar, Sangeeta; Kulkarni, Dinraj

2017-09-01

The aim of this study was to evaluate the stress and discrimination faced by human immunodeficiency virus (HIV)-affected adult patients on antiretroviral therapy (ART) for more than 1 year. A cross-sectional study was carried out among 170 adults on ART, reporting to the ART center of the District Civil Hospital, for more than 1 year in Raichur Taluk, Karnataka, India. Convenience sampling technique was followed. Descriptive statistics was performed (Chi-square test) using Statistical Package for the Social Sciences version 16.0. A total of 156 (91.8%) patients' families had knowledge about their seropositive status. Seventeen (10.9%) HIV-positive patients reported of change in the attitude of their family members. The main reasons for not revealing the HIV status were the internalized stigma and fear of rejection. Women faced greater discrimination from family, friends, and neighbors than men. It is necessary to not undermine the effect of rejection due to HIV. It is the only infection that has so many associated social and psychological norms which we need to tend at the earnest. Till date, there is an existence of condescendence toward treatment approach. The presence of stigma and the fear of being discriminated could be a major hurdle in the rehabilitation of these patients into the mainstream society. Furthermore, it serves as an existing challenge to ascertain these individuals to achieve overall health.

Immunotherapy with an HIV-DNA Vaccine in Children and Adults

PubMed Central

Palma, Paolo; Gudmundsdotter, Lindvi; Finocchi, Andrea; Eriksson, Lars E.; Mora, Nadia; Santilli, Veronica; Aquilani, Angela; Manno, Emma C.; Zangari, Paola; Romiti, Maria Luisa; Montesano, Carla; Grifoni, Alba; Brave, Andreas; Ljungberg, Karl; Blomberg, Pontus; Bernardi, Stefania; Sandström, Eric; Hejdeman, Bo; Rossi, Paolo; Wahren, Britta

2014-01-01

Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals’ immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children’s and adults’ responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4–16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation

Task shifting for the delivery of pediatric antiretroviral treatment: a systematic review.

PubMed

Penazzato, Martina; Davies, Mary-Ann; Apollo, Tsitsi; Negussie, Eyerusalem; Ford, Nathan

2014-04-01

Pediatric antiretroviral treatment coverage in resource-limited settings continues to lag behind adults. Task shifting is an effective approach broadly used for adults, which some countries have also adopted for children, but implementation is limited by lack of confidence and skills among nonspecialist staff. A systematic review was conducted by combining key terms for task shifting, antiretroviral therapy (ART), and children. Five databases and two conferences were searched from inception till August 01, 2013. Eight observational studies provided outcome data for 11,828 children who received ART from nonphysician providers across 10 countries in sub-Saharan Africa. The cumulative pooled proportion of deaths was 3.2% [95% confidence interval (CI): 2.0 to 4.5] at 6 months, 4.6% (95% CI: 2.1 to 7.1) at 12 months, 6.2% (95% CI: 3.7 to 8.8) at 24 months, and 5.9% (95% CI: 3.5 to 8.3) at 36 months. Mortality and loss to follow-up in task-shifting programs were comparable to those reported by programs providing doctor- or specialist-led care. Our review suggests that task shifting of ART care can result in outcomes comparable to routine physician care, and this approach should be considered as part of a strategy to scale-up pediatric treatment. Specialist care will remain important for management of sick patients and complicated cases. Further qualitative research is needed to inform optimal implementation of task shifting for pediatric patients.

New strategies for lowering the costs of antiretroviral treatment and care for people with HIV/AIDS in the United Kingdom

PubMed Central

Gazzard, Brian; Moecklinghoff, Christiane; Hill, Andrew

2012-01-01

In the UK, the annual cost of treatment and care for people with human immunodeficiency virus (HIV)/acquired immune deficiency virus (AIDS) rose by over 600% from £104 million in 1997 to £762 million in 2010; approximately two-thirds of the £762 million cost of treatment and care in 2010 was for the procurement of antiretrovirals and other related drugs. The number of people accessing care for HIV/AIDS rose from 22,000 in 2000 to 65,000 in 2009. Adoption of “test and treat” guidelines for treating all HIV-infected people with antiretrovirals would further increase the burden of costs. Given the current economic situation, there is now a new focus on strategies for treatment and care of people with HIV-1 infection which can maintain efficacy but at a lower cost. In this review, we propose three strategies which could potentially lower the costs of treatment and care, ie, stopping testing CD4 counts for patients with full HIV RNA suppression on antiretroviral treatment and recent CD4 counts above 350 cells/μL; more widespread use of generic antiretrovirals as replacements for patients currently taking patented versions; and use of darunavir-ritonavir monotherapy as a switch option for patients with full HIV RNA suppression on other antiretrovirals and no history of virological failure. However, it is important that high standards of clinical care are maintained despite cost-saving measures. Antiretrovirals with generic alternatives may have toxicity issues, eg, zidovudine and nevirapine. There could be ethical issues in starting patients on these drugs if they are currently tolerating other treatments. The use of darunavir-ritonavir monotherapy is not consistently recommended in international HIV treatment guidelines. PMID:22888265

Coagulation imbalance and neurocognitive functioning in older HIV-positive adults on suppressive antiretroviral therapy.

PubMed

Montoya, Jessica L; Iudicello, Jennifer; Oppenheim, Hannah A; Fazeli, Pariya L; Potter, Michael; Ma, Qing; Mills, Paul J; Ellis, Ronald J; Grant, Igor; Letendre, Scott L; Moore, David J

2017-03-27

The aim of this study was to compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. A cross-sectional study of 66 antiretroviral therapy treated, virally suppressed, HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor and von Willebrand factor), anticoagulation (antithrombin, protein C and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1 and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning. Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4 cell count was 654 cells/μl. Levels of soluble biomarkers of procoagulation, anticoagulation and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the cause of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy, thereby improving

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.

Attitudes toward antiretroviral therapy among African American women.

PubMed

Richter, Donna L; Sowell, Richard L; Pluto, Delores M

2002-01-01

To examine attitudes and beliefs of African American women of childbearing age, living with HIV, about pregnancy and antiretroviral therapy. Focus groups were conducted using an exploratory design with a convenience sample of HIV-infected women in 2 southeastern cities. Thirty-three African American women of childbearing age participated in 5 focus groups. Attitudes and beliefs about antiretroviral therapy were related to the women's willingness to comply with treatment. The challenge for health care providers is to counter women's willingness to "play the odds" of having a noninfected baby without taking antiretrovirals.

Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy.

PubMed

Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio

2017-08-02

The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral

Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era.

PubMed

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

We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. 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. 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/mm(3) (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. 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 conditions and optimize earlier

Protocol for a Randomized Controlled Trial Evaluating Mobile Text Messaging to Promote Retention and Adherence to Antiretroviral Therapy for People Living With HIV in Burkina Faso.

PubMed

Wagner, Natascha; Ouedraogo, Denis; Artavia-Mora, Luis; Bedi, Arjun; Thiombiano, Boundia Alexandre

2016-08-17

Retention in care and adherence to antiretroviral therapy (ART) among people living with human immunodeficiency virus (PLHIV) is a critical challenge in many African countries including Burkina Faso. Delivering text messaging (short message service, SMS) interventions through mobile phones may help facilitate health service delivery and improve patient health. Despite this potential, no evaluations have been delivered for national scale settings to demonstrate the impact of mobile health (mHealth) for PLHIV. This study aims to test the impact of SMS text messaging reminders for PLHIV in Burkina Faso, who are under ART. The evaluation identifies whether patients who receive SMS text messages are more likely to (1) retain in care (measured as a dichotomous variable), (2) adhere to antiretroviral regimens (measured as the number of doses missed in the past 7 days), and (3) experience slower disease progression (measured with T-lymphocytes cells). The second objective is to assess its effects on the frequency of health center visits, physical and psychosocial health, nutrition and whether the type of message (text vs image) and frequency (weekly vs semiweekly) have differential impacts including the possibility of message fatigue over time. This 24-month, wide-scale intervention implements a randomized controlled trial (RCT) to evaluate the impact of four variants of a mHealth intervention versus a control group. Our sample comprises adult patients (>15 years of age) undergoing antiretroviral therapy with access to mobile phone services. Multivariate regression analysis will be used to analyze the effect of the intervention on the study population. Data collection is done at baseline and three follow-up waves 6, 12, and 24 months after the intervention starts. The targeted 3800 patients were recruited between February 2015 and May 2015. But political uncertainty delayed the launch of the intervention until October 2015. Data analysis has not yet started. The first

Traditional, complementary and alternative medicine use by HIV patients a decade after public sector antiretroviral therapy roll out in South Africa: a cross sectional study.

PubMed

Nlooto, Manimbulu; Naidoo, Panjasaram

2016-05-17

The roll out of antiretroviral therapy in the South African public health sector in 2004 was preceded by the politicisation of HIV-infection which was used to promote traditional medicine for the management of HIV/AIDS. One decade has passed since; however, questions remain on the extent of the use of traditional, complementary and alternative medicine (TCAM) by HIV-infected patients. This study therefore aimed at investigating the prevalence of the use of African traditional medicine (ATM), complementary and alternative medicines (CAM) by adult patients in the eThekwini and UThukela Health Districts, South Africa. A cross- sectional study was carried out at 8 public health sector antiretroviral clinics using interviewer-administered semi-structured questionnaires. These were completed from April to October 2014 by adult patients who had been on antiretroviral therapy (ART) for at least three months. Use of TCAM by patients was analysed by descriptive statistics using frequency and percentages with standard error. Where the associated relative error was equal or greater to 0.50, the percentage was rejected as unstable. A p-value <0.05 was estimated as statistically significant. The majority of the 1748 participants were Black Africans (1685/1748, 96.40 %, SE: 0.00045), followed by Coloured (39/1748, 2.23 %, SE: 0.02364), Indian (17/1748, 0.97 %, SE: 0.02377), and Whites (4/1748, 0.23 %, SE: 0.02324), p < 0.05. The prevalence of ATM use varied prior to (382/1748, 21.85 %) and after ART initiation (142/1748, 8.12 %), p <0.05, specifically by Black African females both before (14.41 %) and after uptake (5.49 %), p < 0.05. Overall, 35 Black Africans, one Coloured and one Indian (37/1748, 2.12 %) reported visiting CAM practitioners for their HIV condition and related symptoms post ART. Despite a progressive implementation of a successful antiretroviral programme over the first decade of free antiretroviral therapy in the South African public health sector, the use of

Evaluating the care cascade after antiretroviral therapy initiation in Latin America

PubMed Central

Wolff, Marcelo J; Cortes, Claudia P; Mejìa, Fernando A; Padgett, Denis; Belaunzarán-Zamudio, Pablo; Grinsztejn, Beatriz; Giganti, Mark J; McGowan, Catherine C; Rebeiro, Peter F

2018-01-01

Accelerating antiretroviral therapy (ART) administration, improving retention, and achieving viral suppression in low- and middle-income countries must be prioritized. We evaluated trends and disparities in these milestones in a large Latin American cohort. Adults starting ART (ARTstart) from 2003 to 2014 at Caribbean, Central, and South America network for HIV epidemiology sites were assessed for care cascade outcomes: CD4 cell count >200 cells/mm3 at ARTstart; retention (≥1 visit at one year after ARTstart); viral suppression (≥1 HIV-1 RNA <200 copies/ml at one year after ARTstart). Modified Poisson regression provided adjusted prevalence ratios by age, gender, and HIV transmission risk, accounting for site and year of ARTstart. Proportions achieving ARTstart and suppression improved over time (p < 0.05). Older age was associated with better retention and viral suppression, but not ARTstart at CD4 cell count >200 cells/mm3. Females and men who have sex with men (MSM) were more likely to have CD4 cell count >200 cells/mm3 at ARTstart. Injection drug users (IDUs) were less likely to be retained while MSM were more likely to achieve viral suppression (all p <0.05). Despite improvements in these outcomes over the course of a decade in this cohort, significant disparities existed, disadvantaging younger patients, men, and IDUs. These gaps indicate continued progress in providing early diagnosis and ARTstart remain critical. PMID:28618980

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

Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

PubMed Central

Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

2011-01-01

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication. PMID:22654926

Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee.

PubMed

Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

2011-01-01

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients' comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.

Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study.

PubMed

Cerutti, Bernard; Broers, Barbara; Masetsibi, Motlomelo; Faturiyele, Olatunbosun; Toti-Mokoteli, Likabelo; Motlatsi, Mokete; Bader, Joelle; Klimkait, Thomas; Labhardt, Niklaus D

2016-09-08

Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001). The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001). Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77) and alcohol use disorder (2.73, 95 % CI: 1.68-4.42) were significantly associated with poor adherence. There was, however, no significant association with viral suppression. Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. April 28th 2014; NCT02126696 .

Safety and tolerance of efavirenz in different antiretroviral regimens: results from a national multicenter prospective study in 1,033 HIV-infected patients.

PubMed

Pérez-Molina, José A

2002-01-01

To evaluate the incidence and severity of adverse events (AEs) and treatment interruption (TI) with efavirenz in a population with a high rate of intravenous drug use (IVDU). This was a national, multicenter, and observational study of HIV-infected adult patients who were starting an efavirenz-containing regimen. Evaluations of AEs were made in routine clinical practice at baseline and at least 3 months later. A total of 1,033 patients were included from 60 participating hospitals; 20% were antiretroviral naive. The risk factor for HIV infection was IVDU in 62.3%, and 6.6% of participants were on methadone. AEs affected 29.3% of participants, and treatment was interrupted in 8.23%. The most frequent AEs were CNS disturbances that affected 24.1% participants; these AEs were considered related to efavirenz in 18.5% patients. AEs were not severe, and treatment had to be interrupted in 6% of patients. Other AEs were cutaneous rash (incidence of 5.9%; 2.4% of TI), gastrointestinal disturbances (1.45%; no TI), and elevation of liver function test (0.68%; no TI). Patients taking methadone had more AEs (39.7%), mainly CNS disturbances, and TI (19.1%). Cutaneous rash was more frequent among women. Psychoactive drug consumption, previous history of psychiatric disorders, antiretroviral experience, or previous nevirapine intolerance were not associated with higher incidence of AEs. Safety and tolerance of efavirenz is good in most patients, even in a population with a high rate of IVDU. The most common AEs are CNS disturbances; they are not severe and rarely lead to TI.

A randomized trial of ready-to-use supplementary food versus corn-soy blend plus as food rations for HIV-infected adults on antiretroviral therapy in rural Haiti.

PubMed

Ivers, Louise C; Teng, Jessica E; Jerome, J Gregory; Bonds, Matthew; Freedberg, Kenneth A; Franke, Molly F

2014-04-01

The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities. We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth. A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/µL (interquartile range [IQR], 197-475 cells/µL) for the CSB+ group, and 341 cells/µL (IQR, 213-464/µL) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant. In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti.

Colorado Even Start. 1998-1999 Progress Report.

ERIC Educational Resources Information Center

Anderson, Beckie

Even Start programs integrate early childhood education, adult literacy or basic education, parenting education and support, and parent and child time to help break the cycle of poverty and illiteracy. This report describes the Even Start program in Colorado, and includes evaluation questions and methods. The report presents evaluation findings…

Colorado Even Start. 1997-1998 Progress Report.

ERIC Educational Resources Information Center

Anderson, Beckie

Even Start programs integrate early childhood education, adult literacy or basic education, parenting education and support, and parent and child time together to help break the cycle of poverty and illiteracy. This report describes the Even Start program in Colorado, including evaluation questions and methods. The report also presents evaluation…

Utilization of Medical Treatments and Adherence to Antiretroviral Therapy among HIV-Positive Adults with Histories of Childhood Sexual Abuse

PubMed Central

Hansen, Nathan B.; Kochman, Arlene; Sikkema, Kathleen J.

2009-01-01

Abstract 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. PMID:19260772

Antiretroviral pill count and clinical outcomes in treatment-naïve patients with HIV infection.

PubMed

Young, J; Smith, C; Teira, R; Reiss, P; Jarrín Vera, I; Crane, H; Miro, J M; D'Arminio Monforte, A; Saag, M; Zangerle, R; Bucher, H C

2018-02-01

Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations. © 2017 British HIV Association.

Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania, Uganda and Zambia

PubMed Central

Denison, Julie A.; Koole, Olivier; Tsui, Sharon; Menten, Joris; Torpey, Kwasi; van Praag, Eric; Mukadi, Ya Diul; Colebunders, Robert; Auld, Andrew F.; Agolory, Simon; Kaplan, Jonathan E.; Mulenga, Modest; Kwesigabo, Gideon P.; Wabwire-Mangen, Fred; Bangsberg, David R.

2016-01-01

Objectives To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. Design A cross-sectional study. Methods Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. Results A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Conclusion Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients. PMID:25686684

Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients.

PubMed

Neukam, Karin; Mira, José A; Ruiz-Morales, Josefa; Rivero, Antonio; Collado, Antonio; Torres-Cornejo, Almudena; Merino, Dolores; de Los Santos-Gil, Ignacio; Macías, Juan; González-Serrano, Mercedes; Camacho, Angela; Parra-García, Ginés; Pineda, Juan A

2011-11-01

To compare the frequency of grade 3 or 4 transaminase elevations (TEs) in HIV/hepatitis C virus (HCV) co-infected patients who started a three-antiretroviral drug regimen including efavirenz or a ritonavir-boosted protease inhibitor (PI/r) and the influence of pre-existing significant hepatic fibrosis or cirrhosis. All pre-treated or treatment-naive HIV/HCV co-infected patients who started an antiretroviral regimen including two nucleos(t)ide reverse transcriptase inhibitors along with efavirenz or a PI/r in seven Spanish centres from January 2007 to December 2009 were included in this prospective study. Of 262 patients included in this study, 76 (29%) individuals began antiretroviral therapy (ART) including efavirenz and 186 (71%) a PI/r-based combination. The median (interquartile) follow-up was 14.0 (6.2-23.7) months. A total of 20 (7.6%) patients presented grade 3-4 TEs. Four (1.5%) subjects discontinued ART due to this adverse event. Grade 3-4 TEs were observed in 5 (6.6%) subjects receiving efavirenz and 15 (8.1%) treated with PI/r (P = 0.681). Three (6.5%) patients in the efavirenz group with significant fibrosis developed grade 3-4 TEs versus 2 (8.7%) without pre-existing significant fibrosis (P = 0.743). In the PI/r group, the corresponding figures were 10 (8.8%) and 5 (9.3%), respectively (P = 0.931). The frequency of grade 3-4 TEs associated with efavirenz-based ART combinations under clinical practice conditions is low and similar to that found in patients receiving PI/r currently used in HIV/HCV co-infected patients. The baseline fibrosis stage does not have an impact on the development of TEs caused by these antiretroviral drugs in this population.

Colorado Even Start Progress Report, 2001-2002.

ERIC Educational Resources Information Center

Anderson, Beckie

Even Start programs integrate early childhood education, adult literacy or basic education, parenting education and support, and parent and child time together to help break the cycle of poverty and illiteracy. This progress report describes the Even Start program in Colorado and presents evaluation findings from the 2001-2002 implementation year,…

Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

PubMed Central

Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2014-01-01

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

Broadening the use of antiretroviral therapy: the case for feline leukemia virus

PubMed Central

Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

2011-01-01

Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142

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.

Trends in one-year cumulative incidence of death between 2005 and 2013 among patients initiating antiretroviral therapy in Uganda.

PubMed

Bebell, Lisa M; Siedner, Mark J; Musinguzi, Nicholas; Boum, Yap; Bwana, Bosco M; Muyindike, Winnie; Hunt, Peter W; Martin, Jeffrey N; Bangsberg, David R

2017-07-01

Recent ecological data demonstrate improving outcomes for HIV-infected people in sub-Saharan Africa. Recently, Uganda has experienced a resurgence in HIV incidence and prevalence, but trends in HIV-related deaths have not been well described. Data were collected through the Uganda AIDS Rural Treatment Outcomes (UARTO) Study, an observational longitudinal cohort of Ugandan adults initiating antiretroviral therapy (ART) between 2005 and 2013. We calculated cumulative incidence of death within one year of ART initiation, and fit Poisson models with robust variance estimators to estimate the effect enrollment period on one-year risk of death and loss to follow-up. Of 760 persons in UARTO who started ART, 30 deaths occurred within one year of ART initiation (cumulative incidence 3.9%, 95% confidence interval [CI] 2.7-5.6%). Risk of death was highest for those starting ART in 2005 (13.0%, 95% CI 6.0-24.0%), decreased in 2006-2007 to 4% (95% CI 2.0-6.0%), and did not change thereafter ( P = 0.61). These results were robust to adjustment for age, sex, CD4 cell count, viral load, asset wealth, baseline depression, and body mass index. Here, we demonstrate that one-year cumulative incidence of death was high just after free ART rollout, decreased the following year, and remained low thereafter. Once established, ART programs in President's Emergency Fund for AIDS Relief-supported countries can maintain high quality care.

Mortality during the first year of potent antiretroviral therapy in HIV-1-infected patients in 7 sites throughout Latin America and the Caribbean

PubMed Central

2009-01-01

Background Although nearly 2 million people live with HIV in Latin America and the Caribbean, mortality rates after initiation of highly active antiretroviral therapy (HAART) have not been well-described. Methods 5,152 HIV-infected, antiretroviral-naïve adults from clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru starting HAART during 1996–2007 were included. First-year mortality rates and their association with demographics, regimen, baseline CD4, and clinical stage were assessed. Results Overall 1-year mortality rate was 8.3% (95% confidence interval [CI]:7.6–9.1%), although variable across sites: 2.6, 3.7, 6.0, 13.0, 10.8, 3.5, and 9.8% for clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, respectively. 80% of deaths occurred within the first 6 months. Median baseline CD4 was 107 cells/μL, ranging from 79 (Peru) to 163 (Argentina). Mortality estimates adjusting for CD4 were similar across sites (1.1–2.8% for CD4=200), except for Haiti, 7.5%, and Honduras, 7.0%. Death was associated with lower CD4 (adjusted hazard ratio [HR] for CD4=200 vs CD4=50 was 0.58; 95% CI:0.40–0.85) and clinical AIDS (HR=3.1; 95% CI:2.1–4.5). Conclusions Mortality rates were similar to those reported elsewhere for resource-limited settings. Disease stage at HAART initiation, treatment eligibility criteria, program age, and background mortality rates may explain some variability in prognosis between sites. PMID:19430306

The prevalence of antiretroviral multidrug resistance in highly active antiretroviral therapy-treated patients with HIV/AIDS between 2004 and 2009 in South Korea.

PubMed

Choi, Ju-yeon; Kwon, Oh-Kyung; Choi, Byeong-Sun; Kee, Mee-Kyung; Park, Mina; Kim, Sung Soon

2014-06-01

Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20 types of antiretroviral drugs are used in the treatment of human immunodeficiency virus-infected/acquired immune deficiency syndrome patients in South Korea. Despite the rapid development of various antiretroviral drugs, many drug-resistant variants have been reported after initiating HAART, and the efficiency of HAART is limited by these variants. To investigate and estimate the annual antiretroviral drug resistance and prevalence of antiretroviral multi-class drug resistance in Korean patients with experience of treatment. The amplified HIV-1 pol gene in 535 patients requested for genotypic drug resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and Prevention was sequenced and analyzed annually and totally. The prevalence of antiretroviral drug resistance was estimated based on "SIR" interpretation of the Stanford sequence database. Of viruses derived from 787 specimens, 380 samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3% for PI. The percent of annual drug resistance showed similar pattern and slightly declined except 2004 and 2005. The prevalence of multi-class drug resistance against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI, 10.4%; and NRTI/NNRTI, 21.5%. About 50% and less than 10% of patients infected with HIV-1 have multidrug and multiclass resistance linked to 16 antiretroviral drugs, respectively. The significance of this study lies in its larger-scale examination of the prevalence of drug-resistant variants and multidrug resistance in HAART-experienced patients in South Korea. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical implications of fixed-dose coformulations of antiretrovirals on the outcome of HIV-1 therapy.

PubMed

Llibre, Josep M; Arribas, José R; Domingo, Pere; Gatell, Josep M; Lozano, Fernando; Santos, José R; Rivero, Antonio; Moreno, Santiago; Clotet, Bonaventura

2011-09-10

The substitution by generic equivalents of some of the drugs included in fixed-dose antiretroviral coformulations (FDACs) poses the potential risk of disrupting these combinations and administering the components separately in order to incorporate the new generic drug, which offers a more competitive sales price. This may represent a step backwards in the advances achieved in simplicity and adherence to therapy, posing an increased risk of selective noncompliance of some of the separately administered drug substances. Available antiretroviral drugs must be administered for life in the affected individuals - both children and adults. The FDACs represent a significant advance in the simplification of antiretroviral therapy, facilitating adherence to complex and chronic treatments, and contributing to a quantifiable improvement in patient quality of life. These drug coformulations reduce the risk of treatment error, are associated with a lower risk of hospitalization, and can lessen the possibility of covert monotherapy in situations of selective noncompliance. Thus, FDACs can reduce the risk of selection of HIV-1 resistances, which not only adversely affect the treatment options of the individual patient but also constitute a public health problem, and further increase the cost and complexity of therapy. With the exception of those cases requiring dose adjustments, the preferential use of FDACs should be recommended for the treatment of HIV-1 infection in those situations when the agents included in the coformulation are drugs of choice.

Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

PubMed Central

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

2015-01-01

Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P < 0.001) and high LDL (8.5% vs. 62.6%, P < 0.001) was lower in HIV-positive than HIV-negative subjects, and the prevalence of high TG (33.9% vs. 17.0%, P < 0.001) and low HDL (59.6% vs. 11.2%, P < 0.001) was higher in HIV-positive than HIV-negative subjects. Logistic analysis showed that HIV positivity was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC and high LDL. The mean levels of TC, of LDL and of HDL showed an increasing trend with increasing CD4 count in HIV-positive subjects. Multivariable logistic regression found that lower CD4 count was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC in HIV-positive subjects. Among antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by

The cost of antiretroviral therapy in Haiti

PubMed Central

Koenig, Serena P; Riviere, Cynthia; Leger, Paul; Severe, Patrice; Atwood, Sidney; Fitzgerald, Daniel W; Pape, Jean W; Schackman, Bruce R

2008-01-01

Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART) to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers. PMID:18275615

The Indigenous Red Ribbon Storytelling Study: What does it mean for Indigenous peoples living with HIV and a substance use disorder to access antiretroviral therapy in Saskatchewan?

PubMed Central

Nowgesic, Earl; Meili, Ryan; Stack, Sandra; Myers, Ted

2016-01-01

Indigenous peoples living with HIV are less likely than non-Indigenous peoples living with HIV to access antiretroviral therapy; however, there is not enough contextual information surrounding this issue. The Indigenous Red Ribbon Storytelling Study was conducted in part to examine how Indigenous peoples living with HIV construct and understand their experiences accessing antiretroviral therapy. Our study design was critical Indigenous qualitative research, using the Behavioral Model of Health Services Use and community-based participatory research approaches. The study was conducted in partnership with Indigenous and non-Indigenous organizations. Study participants were adults from two Canadian cities. The study methods included 20 individual and two Indigenous sharing circle interviews, six participant observation sessions, a short survey and thematic analysis. Accessing antiretroviral therapy within the context of living with a substance use disorder was an overarching theme. Indigenous peoples living with HIV felt they had to choose between living with their active substance use disorder and accessing antiretroviral therapy. They felt misunderstood as a person living with a substance use disorder and often felt coerced into using antiretroviral therapy. Despite these challenges, they persevered as Indigenous peoples living with HIV and a substance use disorder. Further research on antiretroviral therapy access among Indigenous peoples living with HIV and a substance use disorder, particularly from the perspective of health service providers, is needed. PMID:27867444

The Indigenous Red Ribbon Storytelling Study: What does it mean for Indigenous peoples living with HIV and a substance use disorder to access antiretroviral therapy in Saskatchewan?

PubMed

Nowgesic, Earl; Meili, Ryan; Stack, Sandra; Myers, Ted

2015-01-01

Indigenous peoples living with HIV are less likely than non-Indigenous peoples living with HIV to access antiretroviral therapy; however, there is not enough contextual information surrounding this issue. The Indigenous Red Ribbon Storytelling Study was conducted in part to examine how Indigenous peoples living with HIV construct and understand their experiences accessing antiretroviral therapy. Our study design was critical Indigenous qualitative research, using the Behavioral Model of Health Services Use and community-based participatory research approaches. The study was conducted in partnership with Indigenous and non-Indigenous organizations. Study participants were adults from two Canadian cities. The study methods included 20 individual and two Indigenous sharing circle interviews, six participant observation sessions, a short survey and thematic analysis. Accessing antiretroviral therapy within the context of living with a substance use disorder was an overarching theme. Indigenous peoples living with HIV felt they had to choose between living with their active substance use disorder and accessing antiretroviral therapy. They felt misunderstood as a person living with a substance use disorder and often felt coerced into using antiretroviral therapy. Despite these challenges, they persevered as Indigenous peoples living with HIV and a substance use disorder. Further research on antiretroviral therapy access among Indigenous peoples living with HIV and a substance use disorder, particularly from the perspective of health service providers, is needed.

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

Retention of antiretroviral naïve patients registered in HIV care in a program clinic in Pune, India

PubMed Central

Ghate, Manisha V.; Zirpe, Sunil S.; Gurav, Nilam P.; Rewari, Bharat B.; Gangakhedkar, Raman R.; Paranjape, Ramesh S.

2014-01-01

Background: Retention in HIV care ensures delivery of services like secondary prevention, timely initiation of treatment, support, and care on a regular basis. The data on retention in pre antiretroviral therapy (ART) care in India is scanty. Materials and Methods: Antiretroviral naïve HIV-infected adult patients registered between January 2011 and March 2012 in HIV care (pre-ART) were included in the study. The follow-up procedures were done as per the national guidelines. Patients who did not report to the clinic for 1 year were considered as pre-ART lost to follow-up (pre-ART LFU). They were contacted either telephonically or by home visits. Logistic regression analysis was done to find out factors associated with pre-ART loss to follow-up. Results: A total of 689 antiretroviral naïve adult patients were registered in the HIV care. Fourteen (2%) patients died and 76 (11%) were LFU till March 2013. The multivariate analysis showed that baseline CD4 count >350 cells/mm3 (P < 0.01) and illiteracy (P = 0.044) were significantly associated with LFU. Of the total pre-ART LFUs, 35 (46.1%) informed that they would visit the clinic at their convenient time. NGOs that referred 16 female sex workers (FSWs) who were LFU (21.1%) informed that they would make efforts to refer them to the clinic. Conclusion: Higher CD4 count and illiteracy were significantly associated with lower retention in pre-ART care. Developing effective “retention package” for patients and strengthening linkage strategies between key sub-population such as FSWs and ART programming will help to plug the leaky cascade in HIV care. PMID:26396447

Scientific Production about the Adherence to Antiretroviral Therapy

PubMed Central

de Oliveira, Regina Célia; de Andrade Moraes, Danielle Chianca; Santos, Cleytiane Stephany Silva; da Silva Monteiro, Gicely Regina Sobral; da Rocha Cabral, Juliana; Beltrão, Roberta Andrade; da Silva, Calos Roberto Lyra

2017-01-01

Objective To identify the elite of authors about the subject adherence to antiretroviral therapy; to identify the journals turned to publishing articles about adherence to antiretroviral therapy; and to identify and analyze the most commonly used words in abstracts of articles about adherence to antiretroviral therapy. Method A bibliometric study conducted through the Scopus base. We used articles published between 1996 and 2014, after application of the eligibility criteria, there were composed the sample with 24 articles. The data were analyzed descriptively. Were used the laws of bibliometric (Lotka, Bradford and Zipf) and the conceptual cloud map of words, through the program Cmap tools. Results Lotka’s Law identified the 5 authors more productive (46% of the total published). Bradford is impaired in this study. Concerning Zipf, 3 zones were determined, 31.47% of the words with in the first zone, 26.46% in the second and 42.06% in the third. In the conceptual map, the words/factors that positively and negatively influence adherence were emphasized, among them the need for more research in the health services. Conclusion There are few publications about the accession to antiretroviral therapy, and the scientific production is in the process of maturation. One can infer that the theme researched is not yet an obsolete topic. It should be noted that the Bibliometric was a relevant statistic tool to generate information about the publications about the antiretroviral therapy. PMID:28979571

Positive provider interactions, adherence self-efficacy, and adherence to antiretroviral medications among HIV infected adults: A mediation model

PubMed Central

Johnson, Mallory O.; Chesney, Margaret A.; Goldstein, Rise B.; Remien, Robert H.; Catz, Sheryl; Gore-Felton, Cheryl; Charlebois, Edwin; Morin, Stephen F.

2008-01-01

Adherence to antiretroviral (ARV) therapy for HIV infection is critical for maximum benefit from treatment and for the prevention of HIV-related complications. There is evidence that many factors determine medication adherence, including adherence self-efficacy (confidence in one's ability to adhere) and relations with health care providers. However, there are no studies that examine how these two factors relate to each other and their subsequent influence on HIV medication adherence. The goal of the current analysis was to explore a model of medication adherence in which the relationship between positive provider interactions and adherence is mediated by adherence self-efficacy. Computerized self administered and interviewer administered self reported measures of medication adherence, demographic and treatment variables, provider interactions, and adherence self-efficacy were administered to 2765 HIV infected adults on ARV. Criteria for mediation were met, supporting a model in which adherence self-efficacy is the mechanism for the relationship between positive provider interactions and adherence. The finding was consistent when the sample was stratified by gender, race, injection drug use history, and whether the participant reported receipt of HIV specialty care. Positive provider interactions may foster greater adherence self-efficacy, which is associated with better adherence to medications. Results suggest implications for improving provider interactions in clinical care, and future directions for clarifying inter-relationships among provider interactions, adherence self-efficacy, and medication adherence are supported. PMID:16623624

Otitis media in Brazilian human immunodeficiency virus infected children undergoing antiretroviral therapy.

PubMed

Miziara, I D; Weber, R; Araújo Filho, B Cunha; Pinheiro Neto, C Diógenes

2007-11-01

To assess changes in the prevalence of otitis media, associated with the use of highly active antiretroviral therapy, in Brazilian human immunodeficiency virus (HIV) infected children. Division of otorhinolaryngology, Hospital das Clínicas, Sao Paulo University Medical School, Brazil. A cohort of 459 HIV-infected children aged below 13 years. The prevalence of otitis media and the serum cluster of differentiation four glycoprotein T lymphocyte count were compared for children receiving highly active antiretroviral therapy (with protease inhibitors) and those receiving standard antiretroviral therapy (without protease inhibitors). Otitis media was present in 33.1 per cent of the children. Children aged from zero years to five years 11 months receiving highly active antiretroviral therapy had a higher prevalence of acute otitis media (p=0.02) and a lower prevalence of chronic otitis media (p=0.02). Children who were receiving highly active antiretroviral therapy had a mean serum cluster of differentiation four glycoprotein T lymphocyte count greater than that of those who were receiving standard antiretroviral therapy (p<0.001). The use of highly active antiretroviral therapy in Brazilian HIV-infected children was associated with a lower prevalence of chronic otitis media.

Impact of antiretroviral therapy on serum lipoprotein levels and dyslipidemias: a systematic review and meta-analysis.

PubMed

Nduka, Chidozie; Sarki, Ahmed; Uthman, Olalekan; Stranges, Saverio

2015-11-15

Antiretroviral drugs increase biosynthesis and reduce hepatic clearance of serum cholesterol. It is thus important to evaluate the impact of antiretroviral treatment on serum lipoprotein levels and the risk of dyslipidemia. We searched EMBASE and PubMed for articles comparing lipid profiles between HIV-infected adult patients naïve and exposed to antiretroviral therapy (ART). Eligible studies were pooled by performing random-effects meta-analyses of mean serum lipoprotein levels and prevalence estimates of dyslipidemias. 51 observational studies comprising 37,110 patients were included in the meta-analyses. ART-exposed patients had significantly higher concentrations of total cholesterol (45 studies, mean difference [MD]=29.4mg/dL, 95% confidence interval [CI] 26.5 to 32.4, I(2)=82.2%), low density lipoprotein-cholesterol (37 studies, MD=14.9mg/dL, 95% CI 11.2 to 18.5, I(2)=86.1%), and triglycerides (43 studies, MD=46.8mg/dL, 95% CI 37.8 to 55.8, I(2)=97.1%), compared with ART-naïve patients. The risks of hypercholesterolemia (25 studies, pooled odds ratio [OR] 3.8, 95% CI 3.1 to 4.7, I(2)=60.0%) and hypertriglyceridemia (21 studies, OR 2.2, 95% CI 1.7 to 2.9, I(2)=81.7%) were also significantly higher among ART-exposed patients, compared with ART-naïve patients. Antiretroviral therapy is significantly associated with increase in serum lipid levels and increased risk of dyslipidemia. Whether or not these associations are causal should be investigated by future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study.

PubMed

Meintjes, Graeme; Dunn, Liezl; Coetsee, Marla; Hislop, Michael; Leisegang, Rory; Regensberg, Leon; Maartens, Gary

2015-01-01

An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme. Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014. 152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5-3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days. Virologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.

Predictors of psychological well-being in a diverse sample of HIV-positive patients receiving highly active antiretroviral therapy.

PubMed

Safren, Steven A; Radomsky, Adam S; Otto, Michael W; Salomon, Elizabeth

2002-01-01

The purpose of the present study was to identify variables relevant to psychological well-being in HIV patients receiving highly active antiretroviral therapy (HAART). Multiple stressors accompany living with HIV while managing a HAART regimen. However, a variety of cognitive and behavioral variables can protect against or augment the deleterious effects of stress in this population. The authors hypothesized that satisfaction with social support, coping styles, and maladaptive attributions about HIV would explain more variance in psychological well-being than stressful life events per se. Participants were individuals with HIV receiving antiretroviral therapy-either starting a new HAART regimen or having difficulties adhering to their current regimen. Satisfaction with social support, coping styles, and punishment beliefs about HIV were uniquely associated with depression, quality of life, and self-esteem over and above the effects of stressful life events. These results provide support for continued psychosocial interventions that target these variables among patients with HIV.

Impact of an antiretroviral stewardship strategy on medication error rates.

PubMed

Shea, Katherine M; Hobbs, Athena Lv; Shumake, Jason D; Templet, Derek J; Padilla-Tolentino, Eimeira; Mondy, Kristin E

2018-05-02

The impact of an antiretroviral stewardship strategy on medication error rates was evaluated. This single-center, retrospective, comparative cohort study included patients at least 18 years of age infected with human immunodeficiency virus (HIV) who were receiving antiretrovirals and admitted to the hospital. A multicomponent approach was developed and implemented and included modifications to the order-entry and verification system, pharmacist education, and a pharmacist-led antiretroviral therapy checklist. Pharmacists performed prospective audits using the checklist at the time of order verification. To assess the impact of the intervention, a retrospective review was performed before and after implementation to assess antiretroviral errors. Totals of 208 and 24 errors were identified before and after the intervention, respectively, resulting in a significant reduction in the overall error rate ( p < 0.001). In the postintervention group, significantly lower medication error rates were found in both patient admissions containing at least 1 medication error ( p < 0.001) and those with 2 or more errors ( p < 0.001). Significant reductions were also identified in each error type, including incorrect/incomplete medication regimen, incorrect dosing regimen, incorrect renal dose adjustment, incorrect administration, and the presence of a major drug-drug interaction. A regression tree selected ritonavir as the only specific medication that best predicted more errors preintervention ( p < 0.001); however, no antiretrovirals reliably predicted errors postintervention. An antiretroviral stewardship strategy for hospitalized HIV patients including prospective audit by staff pharmacists through use of an antiretroviral medication therapy checklist at the time of order verification decreased error rates. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Antiretroviral Therapy Outcomes of HIV-infected children in the TREAT Asia Pediatric HIV Observational Database

PubMed Central

Hansudewechakul, Rawiwan; Sirisanthana, Virat; Kurniati, Nia; Puthanakit, Thanyawee; Lumbiganon, Pagakrong; Yusoff, Nik Khairulddin Nik; Fong, Siew Moy; Nallusamy, Revathy; Srasuebkul, Preeyaporn; Law, Matthew; Sohn, Annette H.; Chokephaibulkit, Kulkanya

2010-01-01

Introduction We report responses to combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database. Methods Children included were those who had received cART (i.e., ≥3 antiretrovirals) at <18 years. The analysis was intention-to-treat by the first cART regimen. Median values are provided with interquartile ranges; hazard ratios (HR) with 95% confidence intervals. Results Of the 1655 children included, 50.4% were male, with a median age at cART of 7.0 (3.9, 9.8) years and CD4 of 8 (2.0, 15)%; 92.5% were started on an NNRTI; median duration of follow-up was 2.9 (1.4, 4.6) years. Loss-to-follow-up and death rates were 4.2 (3.7, 4.8) and 2.1 (1.7, 2.5) per 100 person-years, respectively. At 36 months, median CD4 was 26 (21, 31)%; 81% of those with viral load (N=302) were <400 copies/mL. Children who reached CD4 ≥25% within five years were more likely to be females (HR 1.4; 1.2, 1.7), start before 18 months old (HR 3.8; 2.4, 6.2), lack a history of mono/dual-therapy (HR 1.7; 1.4, 2.5), and have a higher baseline CD4 (per 10% increase: HR 2; 1.9, 2.2). Conclusion These data underscore the need for early diagnosis and cART initiation to preserve immune function. PMID:20842043

Brain tumor - primary - adults

MedlinePlus

... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

Hypophosphataemia with non-tenofovir-containing antiretroviral therapy.

PubMed

Wainwright, E; Sherrard, J; Duncan, S; Shine, B; Dorrell, L

2013-07-01

Hypophosphataemia with tenofovir (TDF) treatment has been well described. The role of HIV infection and of other antiretroviral (ART) agents in hypophosphataemia has received less attention. The aim of this study was to determine the prevalence of hypophosphataemia in HIV-positive adults. We measured the fasting plasma phosphate level and estimated glomerular filtration rate (eGFR) in 123 HIV-positive patients. A total of 26% had hypophosphataemia and 11% had hypophosphataemia of grades 2-4 (0.65 mmol/L or less). Hypophosphataemia of any grade was more frequent in those who were ART-treated than ART-naive (35% versus 10%; P = 0.0001). Multiple linear regression analysis showed no significant association between phosphate level and gender, TDF status, duration of ART, duration of HIV infection and eGFR. Increasing age was significantly associated with a very small rise in phosphate level. Isolated hypophosphataemia was significantly more frequent in HIV-positive subjects receiving ART than ART-naive individuals, irrespective of the drug regimen.

[Assessment of factors associated with patients' comprehension of treatment at the start of antiretroviral therapy].

PubMed

Braga Ceccato, Maria das Graças; Acurcio, Francisco de Assis; Vallano, Antonio; Comini César, Cibele; Crosland Guimarães, Mark Drew

2009-01-01

The aim of this study was to evaluate factors associated with patients' comprehension of antiretroviral therapy (ART). Cross-sectional analysis in which patients at 2 HIV/AIDS public referral centers (Belo Horizonte, Brazil) were interviewed after initiating ART. Information was recorded on variables related to the patient's characteristics, the treatment prescribed, and the healthcare professional involved. A score indicating the patients' level of comprehension regarding the medications prescribed was obtained using a latent trait model estimated by the item response theory. A total of 406 patients were interviewed. Mean (SD) age was 35 (10) years, 227 were men (56%), 302 of Afro-American ethnicity (77%), and 213 had <8 years of education (53%). The regression model determined that 52.25% of the variability of comprehension was explained by the individual's characteristics. Variables associated (P<0.05) with poorest understanding about ART were lower education (<8 years), lack of knowledge about treatment duration and clinical severity, inadequate information provided by physicians, inability to understand pharmaceutical information, daily number of tablets, and the ART regimen prescribed. Comprehension of information about the ART regimen prescribed varies considerably between individuals. Nonetheless, several factors were found to be associated with the level of understanding: characteristics of the patient (education, clinical severity), characteristics of treatment (daily number of tablets, ART regimen prescribed), and contribution of healthcare professionals (information from physicians and pharmacists). Strategies to reinforce information about ART should be a priority for patients with a low level of understanding.

What to Start: Selecting a First HIV Regimen

MedlinePlus

... to treat HIV infection is called antiretroviral therapy (ART). People on ART take a combination of HIV medicines (called an ... infection. HIV treatment (also called antiretroviral therapy or ART) begins with choosing an HIV regimen. People on ...

Protocol for a Randomized Controlled Trial Evaluating Mobile Text Messaging to Promote Retention and Adherence to Antiretroviral Therapy for People Living With HIV in Burkina Faso

PubMed Central

Ouedraogo, Denis; Artavia-Mora, Luis; Bedi, Arjun; Thiombiano, Boundia Alexandre

2016-01-01

Background Retention in care and adherence to antiretroviral therapy (ART) among people living with human immunodeficiency virus (PLHIV) is a critical challenge in many African countries including Burkina Faso. Delivering text messaging (short message service, SMS) interventions through mobile phones may help facilitate health service delivery and improve patient health. Despite this potential, no evaluations have been delivered for national scale settings to demonstrate the impact of mobile health (mHealth) for PLHIV. Objectives This study aims to test the impact of SMS text messaging reminders for PLHIV in Burkina Faso, who are under ART. The evaluation identifies whether patients who receive SMS text messages are more likely to (1) retain in care (measured as a dichotomous variable), (2) adhere to antiretroviral regimens (measured as the number of doses missed in the past 7 days), and (3) experience slower disease progression (measured with T-lymphocytes cells). The second objective is to assess its effects on the frequency of health center visits, physical and psychosocial health, nutrition and whether the type of message (text vs image) and frequency (weekly vs semiweekly) have differential impacts including the possibility of message fatigue over time. Methods This 24-month, wide-scale intervention implements a randomized controlled trial (RCT) to evaluate the impact of four variants of a mHealth intervention versus a control group. Our sample comprises adult patients (>15 years of age) undergoing antiretroviral therapy with access to mobile phone services. Multivariate regression analysis will be used to analyze the effect of the intervention on the study population. Data collection is done at baseline and three follow-up waves 6, 12, and 24 months after the intervention starts. Results The targeted 3800 patients were recruited between February 2015 and May 2015. But political uncertainty delayed the launch of the intervention until October 2015. Data

Outcomes of antiretroviral treatment: a comparison between hospitals and health centers in Ethiopia.

PubMed

Balcha, Taye T; Jeppsson, Anders

2010-01-01

the objective of this study was to compare the outcomes of antiretroviral therapy (ART) between hospital and health center levels in Ethiopia. medical records of 1709 ART patients followed for 24 months at 2 hospitals and 3 health centers in the Oromia region of Ethiopia were reviewed. Noted outcomes of ART were currently alive and on treatment; lost to follow-up (LTFU); transferred out (TO); and died (D). of 1709 HIV-positive patients started on ART between September 2006 and February 2007, 1044 (61%) remained alive and were on treatment after 24-month follow-up. In all, 835 (57%) of ART patients at hospitals and 209 (83%) at health centers were retained in the program. Of those who were alive and receiving ART, 79% of patients at health centers and 72% at hospitals were clinically or immunologically improving. In addition, 331 (23%) patients at hospitals were LFTU as compared to 24 (10%) of patients at health centers (relative risk [RR] at 95% confidence interval [CI]: .358 [.231-.555]). While 11% was the mortality rate at hospitals, 5% of patients at health centers also died (RR at 95% CI: .360 [.192-.673]). antiretroviral therapy at health centers was associated with more favorable outcomes than at hospitals.

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

PubMed

Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

HIV/hepatitis C virus and HIV/hepatitis B virus coinfections protect against antiretroviral-related hyperlipidaemia.

PubMed

Diong, C; Raboud, Jm; Li, M; Cooper, C

2011-08-01

Hyperlipidaemia is a recognized complication of HIV antiretroviral therapy. The interactions among HIV, viral hepatitis, antiretroviral therapies and lipids are poorly understood. Ontario HIV Treatment Network Cohort Study participants with at least one lipid level after highly active antiretroviral therapy (HAART) initiation were assessed. Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-coinfected patients were identified by serology or chart review. HCV antiviral recipients, diabetics and those on lipid-lowering drugs at baseline were excluded from the study. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid-lowering drug use were assessed by multivariate logistic regression. A total of 1587 HIV-monoinfected, 190 HIV/HBV-coinfected and 255 HIV/HCV-coinfected patients were evaluated. Most were male (85-92% for the 3 groups evaluated: HIV, HIV/HBV, HIV/HCV). The median [interquartile range (IQR)] age at HAART initiation was 48 (44-56) years and was similar between groups. The median (IQR) CD4 count at HAART initiation was 245 (120-370) cells/μL in HIV-monoinfected participants, 195 (110-330) cells/μL in HIV/HBV-coinfected participants and 268 (140-409) cells/μL in HIV/HCV-coinfected participants. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid-lowering drug use included HIV/HCV coinfection [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.34, 0.61; P<0.0001], HIV/HBV coinfection (OR 0.74; 95% CI 0.55, 0.99; P=0.04), year of starting HAART after 2004 vs. 1997 or earlier (OR 0.37; 95% CI 0.29, 0.48; P<0.0001) and year of starting HAART between 1998 and 2003 vs. 1997 or earlier (OR 0.75; 95% CI 0.61, 0.92; P<0.01). Factors associated with increased risk included age (OR 1.55; 95% CI 1.39, 1.72; per 10 years, P<0.0001) and male gender (OR 1.84; 95% CI 1.36, 2.48; P<0.0001). HIV/HCV and to a lesser extent HIV/HBV coinfections are protective against HAART-related hyperlipidaemia. © 2011

Durability of Adherence to Antiretroviral Therapy on Initial and Subsequent Regimens

PubMed Central

GARDNER, EDWARD M.; BURMAN, WILLIAM J.; MARAVI, MOISES E.; DAVIDSON, ARTHUR J.

2007-01-01

There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, −43% per year), followed by patients with intermediate regimen duration (16 to <28 months, −19% per year), and then patients with longer regimens (≥28 months, −5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed. PMID:16987049

Adipocytes Impair Efficacy of Antiretroviral Therapy

PubMed Central

Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

2018-01-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

Health and labor supply in the context of HIV/AIDS: the long-run economic impacts on antiretroviral therapy*

PubMed Central

Thirumurthy, Harsha; Zivin, Joshua Graff

2011-01-01

Using longitudinal survey data collected in Kenya, this paper estimates the longer-term impacts of antiretroviral therapy (ART) on the labor supply of treated adults and their household members. Building upon previous work in Kenya, data collected from 2004–2006 indicate that early evidence on the short-run impacts of ART tends to be upheld over the long-term as well. The results show that the labor supply response among treated adults occurs rapidly and is sustained through the 3-year observation period in our study. These results underscore the strong relationship between health and labor supply that has been observed in other contexts. PMID:22984292

Factors influencing utilization of postpartum CD4 count testing by HIV-positive women not yet eligible for antiretroviral treatment.

PubMed

Gilles, Kate P; Zimba, Chifundo; Mofolo, Innocent; Bobrow, Emily; Hamela, Gloria; Martinson, Francis; Hoffman, Irving; Hosseinipour, Mina

2011-03-01

Delayed antiretroviral initiation is associated with increased mortality, but individuals frequently delay seeking treatment. To increase early antiretroviral therapy (ART) enrollment of HIV-positive women, antenatal clinics are implementing regular, postpartum CD4 count testing. We examined factors influencing women's utilization of extended CD4 count testing. About 53 in-depth interviews were conducted with nurses, patients, social support persons, and government health officials at three antenatal clinics in Lilongwe, Malawi. Counseling and positive interactions with staff emerged as facilitating factors. Women wanted to know their CD4 count, but didn't understand the importance of early ART initiation. Support from husbands facilitated women's return to the clinic. Reminders were perceived as helpful but ineffectively employed. Staff identified lack of communication, difficulty in tracking, and referring women as barriers. Counseling messages should emphasize the importance of starting ART early. Clinics should focus on male partner involvement, case management, staff communication, and appointment reminders. Follow-up should be offered at multiple service points.

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

Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment.

PubMed

Murillo, Wendy; de Rivera, I L; Parham, L; Jovel, E; Palou, E; Karlsson, A C; Albert, J

2010-02-01

The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

Outcomes of Antiretroviral Treatment in Programmes with and without Routine Viral Load Monitoring in Southern Africa

PubMed Central

Keiser, Olivia; Chi, Benjamin H.; Gsponer, Thomas; Boulle, Andrew; Orrell, Catherine; Phiri, Sam; Maxwell, Nicola; Maskew, Mhairi; Prozesky, Hans; Fox, Matthew P; Westfall, Andrew; Egger, Matthias

2013-01-01

Objectives To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with Malawi and Zambia, where monitoring is based on CD4 cell counts. Methods We included 18,706 adult patients starting ART in South Africa and 80,937 patients starting in Zambia or Malawi. We examined CD4 responses in models for repeated measures, and the probability of switching to second-line regimens, mortality and loss to follow-up in multi-state models, measuring time from six months. Findings In South Africa 9.8% (9.1–10.5%) had switched at 3 years, 1.3% (95% CI 0.9–1.6%) remained on failing first-line regimens, 9.2% (8.5–9.8%) were lost to follow-up and 4.3% (3.9–4.8%) had died. In Malawi and Zambia more patients were on a failing first-line regimen (3.7%, 3.6–3.9%), fewer patients had switched (2.1%, 2.0–2.3%) and more patients were lost (15.3%, 15.0–15.6%) or had died (6.3%, 6.0–6.5%). Median CD4 cell counts were lower in South Africa at start of ART (93 vs. 132 cells/µL, p<0.001) but higher after 3 years (425 vs. 383 cells/µL, p<0.001). The hazard ratio comparing South Africa with Malawi and Zambia, adjusted for age, sex, first-line regimen and CD4 cell count, was 0.58 (95% CI 0.50–0.66) for death and 0.53 (0.48–0.58) for loss to follow-up. Conclusions Over 3 years of ART mortality was lower in South Africa than in Malawi or Zambia. The more favourable outcome in South Africa might be explained by viral load monitoring leading to earlier detection of treatment failure, adherence counselling and timelier switching to second-line ART. PMID:21681057

HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy

PubMed Central

Heaton, R.K.; Clifford, D.B.; Franklin, D.R.; Woods, S.P.; Ake, C.; Vaida, F.; Ellis, R.J.; Letendre, S.L.; Marcotte, T.D.; Atkinson, J.H.; Rivera-Mindt, M.; Vigil, O.R.; Taylor, M.J.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T.L.; Wong, J.; Grant, I.

2010-01-01

Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. GLOSSARY ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CHARTER = CNS HIV Antiretroviral Therapy Effects Research; CIDI = Composite International Diagnostic Interview; CLIA = Clinical Laboratory Improvement Amendments; CPE = CNS penetration effectiveness; HAD = HIV-associated dementia; HAND = HIV

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting.

PubMed

Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

2014-01-01

In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/μL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71-€33,570.00) and €14,277.00 (range: €5,908.89-€82

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting

PubMed Central

Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

2014-01-01

Objective In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. Methods The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. Results A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/μL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71–€33,570.00) and €14,277.00 (range

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

Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study

PubMed Central

Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Binelli, Andrea; De Castro, Paola; Terlizzi, Roberta; Fucili, Luca; Di Gregorio, Massimiliano; Mirra, Marco; Olivieri, Erika; Teklu, Tsigemariam; Zegeye, Teame; Haile, Amanuel; Vella, Stefano; Abraham, Loko; Godefay, Hagos

2015-01-01

Introduction Although Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia. Methods We used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation. Results The four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition. Conclusions Although Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific

Profile of CD4 counts and symptoms in HIV positive patients on and not on antiretroviral therapy.

PubMed

Wal, N; Venkatesh, V; Agarwal, G G; Tripathi, A K

2011-03-01

This communication pertains to a study on analysis of the profile of CD4 counts and symptoms in HIV infected adult subjects on and not on antiretroviral therapy. Clinical symptoms in HIV infected patients attending a tertiary care hospital in north India were recorded by direct questioning. Differences in distribution of categorical variables were analyzed using chi-square test. A p-value < 0.05 was considered statistically significant. 317 enrolled HIV positive patients, 271/317 (85.5%) patients were symptomatic. The common symptoms were weakness (65.6%), bodyache and joint pain (63.4%), lethargy and fatigue (62.5%), prolonged fever (53.3%), weight loss (47.6%), cough (44.5%), loss of appetite (44.2%) and chronic diarrhoea (40.1%). Most symptoms were found significantly less frequently in patients on antiretroviral therapy (ART). High CD4+ T-cell counts were negatively associated with symptoms. The overall proportion of symptomatic patients was significantly higher than the number with an etiologically documented opportunistic infections (32.5%). Pulmonary tuberculosis (30.9%) was the most frequently documented opportunistic infection. Antiretroviral therapy appears to be beneficial in reducing symptoms in HIV positive patients. Affordable high quality laboratory diagnostic facilities for the diagnosis of opportunistic infections under the public health program will help to obtain an accurate picture of the range of opportunistic infections in HIV patients in India.

Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

PubMed Central

Cesar, Carina; Koethe, John R; Giganti, Mark J; Rebeiro, Peter; Althoff, Keri N; Napravnik, Sonia; Mayor, Angel; Grinsztejn, Beatriz; Wolff, Marcelo; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Sterling, Timothy R; Willig, James; Levison, Julie; Kitahata, Mari; Rodriguez-Barradas, Maria C; Moore, Richard D; McGowan, Catherine; Shepherd, Bryan E; Cahn, Pedro

2016-01-01

Introduction Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. PMID:26996992

Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America.

PubMed

Cesar, Carina; Koethe, John R; Giganti, Mark J; Rebeiro, Peter; Althoff, Keri N; Napravnik, Sonia; Mayor, Angel; Grinsztejn, Beatriz; Wolff, Marcelo; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Sterling, Timothy R; Willig, James; Levison, Julie; Kitahata, Mari; Rodriguez-Barradas, Maria C; Moore, Richard D; McGowan, Catherine; Shepherd, Bryan E; Cahn, Pedro

2016-01-01

Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.

[Sustainability of Brazilian policy for access to antiretroviral drugs].

PubMed

Grangeiro, Alexandre; Teixeira, Luciana; Bastos, Francisco I; Teixeira, Paulo

2006-04-01

The expense of acquiring antiretroviral drugs in Brazil has given rise to debate about the sustainability of the policy of universal access to AIDS medications, despite the evident benefits. The objective of this study was to analyze the evolution of the Ministry of Health's spending on acquiring antiretroviral drugs from 1998 to 2005, the determining factors and the medium-term sustainability of this policy (2006-2008). The study on the evolution of spending on antiretrovirals included analysis of their prices, the year-by-year expenditure, the number of patients utilizing the medication, the mean expenditure per patient and the strategies for reducing the prices maintained during this period. To analyze the sustainability of the policy for access to antiretrovirals, the cost of acquiring the drugs over the period from 2006 to 2008 was estimated, along with the proportion of gross domestic product and federal health expenditure represented by this spending. The data were collected from the Ministry of Health, the Brazilian Institute for Geography and Statistics (IBGE) and the Ministry of Planning. The expenditure on antiretrovirals increased by 66% in 2005, breaking the declining trend observed over the period from 2000 to 2004. The main factors associated with this increase were the weakening of the national generics industry and the unsatisfactory results from the process of negotiating with pharmaceutical companies. The Brazilian policy for universal access is unsustainable at the present growth rates of the gross domestic product, unless the country compromises its investments in other fields.

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

PubMed

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

2018-05-01

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

HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report.

PubMed

Frange, Pierre; Faye, Albert; Avettand-Fenoël, Véronique; Bellaton, Erianna; Descamps, Diane; Angin, Mathieu; David, Annie; Caillat-Zucman, Sophie; Peytavin, Gilles; Dollfus, Catherine; Le Chenadec, Jerome; Warszawski, Josiane; Rouzioux, Christine; Sáez-Cirión, Asier

2016-01-01

Durable HIV-1 remission after interruption of combined antiretroviral therapy (ART) has been reported in some adults who started treatment during primary infection; however, whether long-term remission in vertically infected children is possible was unknown. We report a case of a young adult perinatally infected with HIV-1 with viral remission despite long-term treatment interruption. The patient was identified in the ANRS EPF-CO10 paediatric cohort among 100 children infected with HIV perinatally who started ART before 6 months of age. HIV RNA viral load and CD4 cell counts were monitored from birth. Ultrasensitive HIV RNA, peripheral blood mononuclear cell (PBMC)-associated HIV DNA, HIV-specific T-cell responses (ie, production of cytokines and capacity to suppress HIV infection), reactivation of the CD4 cell reservoir (measured by p24 ELISA and HIV RNA in supernatants upon phytohaemagglutinin activation of purified CD4 cells), and plasma concentrations of antiretroviral drugs were assessed after 10 years of documented control off therapy. The infant was born in 1996 to a woman with uncontrolled HIV-1 viraemia and received zidovudine-based prophylaxis for 6 weeks. HIV RNA and DNA were not detected 3 days and 14 days after birth. HIV DNA was detected at 4 weeks of age. HIV RNA reached 2·17× 10(6) copies per mL at 3 months of age and ART was started. HIV RNA was undetectable 1 month later. ART was discontinued by the family at some point between 5·8 and 6·8 years of age. HIV RNA was undetectable at 6·8 years of age and ART was not resumed. HIV RNA has remained below 50 copies per mL and CD4 cell counts stable through to 18·6 years of age. After 11·5 years of control off treatment, HIV RNA was below 4 copies per mL and HIV DNA was 2·2 log10 copies per 10(6) PBMCs. The HLA genotype showed homozygosity at several loci (A*2301-, B*1503/4101, C*0210/0802, DRB1*1101-, and DQB1*0602-). HIV-specific CD8 T-cell responses and T-cell activation were weak. Findings

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. © The Author(s) 2014.

Inadequate pre-antiretroviral care, stock-out of antiretroviral drugs and stigma: policy challenges/bottlenecks to the new WHO recommendations for earlier initiation of antiretroviral therapy (CD<350 cells/microL) in eastern Uganda.

PubMed

Muhamadi, Lubega; Nsabagasani, Xavier; Tumwesigye, Mbona Nazarius; Wabwire-Mangen, Fred; Ekström, Anna-Mia; Peterson, Stefan; Pariyo, George

2010-10-01

This study explores reasons for late ART initiation among known HIV positive persons in care from a client/caretaker perspective in eastern Ugandan where ART awareness is presumably high yet AIDS related mortality is a common function of late initiation of ARVs. In Iganga, Uganda we conducted in-depth interviews with clients who started ART at 50-200 CD4 cells/microL and those initiated very late at CD4<50 cells/microL. Focus-group discussions were also conducted with caretakers of clients on ART. Content analysis was performed to identify recurrent themes. ARV stock-outs, inadequate pre-antiretroviral care and lack of staff confidentiality were system barriers to timely ART initiation. Weak social support and prevailing stigma and misconceptions about ARVs as drugs designed to kill, cause cancer, infertility or impotence were other important factors. If the new WHO recommendations (start ART at CD4 350 cells/microL) should be feasible, PLHIV/communities need sensitization about the importance of regular pre-ARV care through the local media and authorities. The ARV supply chain and staff attitudes towards client confidentiality must also be improved in order to encourage timely ART initiation. PLHIV/communities should be sensitization about drug package labeling and the use and importance of ARVs. Stronger social support structures must be created through public messages that fight stigma, enhance acceptance of PLHIV and encourage timely ART initiation. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Adipocytes impair efficacy of antiretroviral therapy.

PubMed

Couturier, Jacob; Winchester, Lee C; Suliburk, James W; Wilkerson, Gregory K; Podany, Anthony T; Agarwal, Neeti; Xuan Chua, Corrine Ying; Nehete, Pramod N; Nehete, Bharti P; Grattoni, Alessandro; Sastry, K Jagannadha; Fletcher, Courtney V; Lake, Jordan E; Balasubramanyam, Ashok; Lewis, Dorothy E

2018-06-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Predictors of mortality among HIV infected patients taking antiretroviral treatment in Ethiopia: a retrospective cohort study

PubMed Central

2012-01-01

Background Studies indicate that there is high early mortality among patients starting antiretroviral treatment in sub-Saharan Africa. However, there is paucity of evidence on long term survival of patients on anti-retroviral treatment in the region. The objective of this study is to examine mortality and its predictors among a cohort of HIV infected patients on anti-retroviral treatment retrospectively followed for five years. Methods A retrospective cohort study was conducted among HIV infected patients on ART in eastern Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate factors that influence time to death and survival over time. Result A total of 1540 study participants were included in the study. From the registered patients in the cohort, the outcome of patients as active, deceased, lost to follow up and transfer out was 1005 (67.2%), 86 (5.9%), 210 (14.0%) and 192 (12.8%) respectively. The overall mortality rate provides an incidence density of 2.03 deaths per 100 person years (95% CI 1.64 - 2.50). Out of a total of 86 deaths over 60 month period; 63 (73.3%) died during the first 12 months, 10 (11.6%) during the second year, and 10 (11.6%) in the third year of follow up. In multivariate analysis, the independent predictors for mortality were loss of more 10% weight loss, bedridden functional status at baseline, ≤ 200 CD4 cell count/ml, and advanced WHO stage patients. Conclusion A lower level of mortality was detected among the cohort of patients on antiretroviral treatment in eastern Ethiopia. Previous history of weight loss, bedridden functional status at baseline, low CD4 cell count and advanced WHO status patients had a higher risk of death. Early initiation of ART, provision of nutritional support and strengthening of the food by prescription initiative, and counseling of patients for early presentation to treatment is recommended. PMID:22606951

R57K Polymorphism in the Human Immunodeficiency Virus Type 1 Protease as Predictor of Early Virological Failure in a Cohort of Antiretroviral-Naive Patients Treated Mostly with a Nelfinavir-Containing Regimen

PubMed Central

Masquelier, Bernard; Droz, Cecile; Dary, Martin; Perronne, Christian; Ferré, Virginie; Spire, Bruno; Descamps, Diane; Raffi, François; Brun-Vézinet, Françoise; Chêne, Geneviève

2003-01-01

In 243 antiretroviral-naive human immunodeficiency-infected patients starting a first-line-protease inhibitor (mainly nelfinavir)-containing therapy, the presence of the polymorphism R57K in the protease at the inception of therapy was independently associated with a higher rate of virological failure. PMID:14576131

The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.

PubMed

Vella, Stefano; Schwartländer, Bernard; Sow, Salif Papa; Eholie, Serge Paul; Murphy, Robert L

2012-06-19

HIV/AIDS not only represents the most severe epidemic in modern times, but also the greatest public health challenge in history. The response of the scientific community has been impressive and in just a few years, turned an inevitably fatal disease into a chronic manageable although not yet curable condition. The development of antiretroviral therapy is not only the history of scientific advancements: it is the result of the passionate 'alliance' towards a common goal between researchers, doctors and nurses, pharmaceutical industries, regulators, public health officials and the community of HIV-infected patients, which is rather unique in the history of medicine. In addition, the rapid and progressive development of antiretroviral therapy has not only proven to be life-saving for many millions but has been instrumental in unveiling the inequities in access to health between rich and poor countries of the world. Optimal benefits indeed, are not accessible to all people living with HIV, with challenges to coverage and sustainability in low and middle income countries. This paper will review the progress made, starting from the initial despairing times, till the current battle towards universal access to treatment and care for all people living with HIV.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

PubMed

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C

2008-11-30

To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Observational cohort study of patients initiating ART between January 2000 and December 2005. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?

PubMed Central

Koethe, John R.; Blevins, Meridith; Nyirenda, Christopher K.; Kabagambe, Edmond K.; Chiasera, Janelle M.; Shepherd, Bryan E.; Zulu, Isaac; Heimburger, Douglas C.

2013-01-01

Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI <18.5 kg/m2, 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; P = 0.01) after adjusting for sex, age, and CD4+ lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m2 (OR 0.96, 95% CI: 0.76 to 1.21; P = 0.74). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed. PMID:23691292

Antiretroviral Regimens and CD4/CD8 Ratio Normalization in HIV-Infected Patients during the Initial Year of Treatment: A Cohort Study

PubMed Central

De Salvador-Guillouët, F.; Sakarovitch, C.; Durant, J.; Risso, K.; Demonchy, E.; Roger, P. M.; Fontas, E.

2015-01-01

Background As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort. Methods We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined. Results 567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ≥1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization [OR, 7.67 (2.54–23.2)]. Conclusions Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”. PMID:26485149

Process and Outcomes Evaluation of an Even Start Program.

ERIC Educational Resources Information Center

Meehan, Merrill L.; Walsh, Sandra; Swisher, Angie; Spring, Janet; Lewis, Harry

The Even Start Family Literacy Program is a national program that addresses the literacy and educational needs of adults in eligible families, teaches effective parenting skills, and addresses the preschool readiness needs of young children in the family. The Monongalia County (West Virginia) Even Start Program was unusual in that it took place in…

Adverse effects of antiretroviral therapy for HIV infection.

PubMed

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

2004-01-20

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Adverse effects of antiretroviral therapy for HIV infection

PubMed Central

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.

2004-01-01

LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART

PubMed Central

Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C.; Rivera-Morales, Lydia G.; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J.; Ramirez, Teresa J.; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M.; Vazquez-Martinez, Carlos A.; Rodriguez-Padilla, Cristina

2016-01-01

Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM’s) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM’s in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM’s during STI. PMID:26807922

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis.

PubMed

Kratz, Jeremy D; El-Shazly, Ahmad Y; Mambuque, Santos G; Demetria, Elpidio; Veldkamp, Peter; Anderson, Timothy S

2016-12-01

Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.

Starting Over: Characteristics of Adult Literacy Learners.

ERIC Educational Resources Information Center

Smith-Burke, M. Trika; And Others

A study examined the characteristics of those individuals who participate in New York City's adult literacy programs. Interviews were conducted with 32 native-born U.S. citizens (native speakers of English) who had enrolled in a literacy program for the first time and had been reading somewhere up to the 4.9 grade level at the time they entered…

A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 - 2011.

PubMed

Dube, Nomathemba Michell; Summers, Robert; Tint, Khin-San; Mayayise, Guistee

2012-01-01

Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. After HAART initiation, with an average lapse of 17.8 months (range: 0 - 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should introduce less toxic first-line ARV regimens

[New and "old" antiretroviral drugs in Pediatrics: new doses, formulations and associations].

PubMed

Villarroel B, Julia

2010-10-01

Of the 25 antiretroviral drugs available in the market, only 16 are allowed for prescription in the pediatric patients. The antiretroviral, pertaining to the first three families, used for two decades, remain valid and are important components of antiretroviral therapy in naive children. We describe doses, presentations and current associations for these drugs in children, and also discuss new co-formulations that will reduce the number of doses, improve tolerance and therefore achieve better adherence of pediatric patients.

Measuring adherence to antiretroviral treatment: the role of pharmacy records of drug withdrawals.

PubMed

Gutierrez, Eliana Battaggia; Sartori, Ana Marli Christovam; Schmidt, Ana Lucia; Piloto, Bruna Mamprim; França, Bruna Biagi; de Oliveira, Adriana Santos; Pouza, Adriana Rodrigues; Moreno, Roberta Vilela; de Melo Picone, Camila; de Almeida Ribeiro, Manoel Carlos Sampaio

2012-08-01

This study aimed to evaluate adherence to antiretroviral treatment (ART) among HIV + adults, assess its association with HIV viral load (VL) and identify factors associated to adherence. A survey involving a random sample of adults followed at a HIV/AIDS reference center in São Paulo city, Brazil, from 2007 to 2009 was done. A questionnaire was applied and data were retrieved from the pharmacy and medical records. The study involved 292 subjects: 70.2% men; median age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all prescribed pills in the last 3 days but only 39.3% picked up ≥95% of the prescribed ART from the pharmacy in the last 12 months. At the multivariate analysis having symptoms prior to ART, taking fewer ART pills, and not missing medical appointments were independently associated to higher adherence. Adherence was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL did not differ from 80 to ≥95% of adherence.

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 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). Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2013; all rights reserved.

Predictors of Survival among Adult Ethiopian Patients in the National ART Program at Seven University Teaching Hospitals: A Prospective Cohort Study.

PubMed

Fekade, Daniel; Weldegebreal, Teklu; Teklu, Alula M; Damen, Melake; Abdella, Saro; Baraki, Nega; Belayhun, Bekele; Berhan, Eyoel; Kebede, Amha; Assefa, Yibeltal

2017-02-01

In Ethiopia, the publicly funded antiretroviral treatment (ART) program was started in 2005. Two hundred seventy-five thousand patients were enrolled in the national ART program by 2012. However, there is limited data on mortality and predictors of death among adult patients in the ART program. The study aimed to estimate mortality and risk factors for death among adult, ART-naïve patients, started in the national ART program from January 2009 to July 2013. Multi-site, prospective, observational cohort study of adult, age > 18 years, ART-naïve patients, started in the national ART program at seven university-affiliated hospitals from January 2009 - July 2013. Kaplan-Meier and Cox regression analyses were used to estimate survival and determine risk factors for death. A total of 976 patients, 594 females (60.9 %), were enrolled into the study. Median age of the cohort was 33years. The median CD4 count at start of ART was 144 cells/µl (interquartile range (IQR) 78-205), and 34.2% (330/965) had CD4 < 100. Sixty-three percent (536/851) had viral load greater than 5 log copies/ml (IQR 4.7-5.7) at base line. One hundred and one deaths were recorded during follow-up period, all-cause mortality rate 10.3%; 5.4 deaths/100 person years of observation, 95% confidence interval 4.4-6.5. Seventy percent of the deaths occurred within six months of starting ART. Cox regression analyses showed that the following measures independently predicted mortality: age >51 years, (Adjusted Hazard Ratio (AHR) 4.01, P=0.003), WHO stages III&IV, (AHR 1.76, p = 0.025), CD4 count, <100, (AHR 2.36, p =0.006), and viral load >5 log copies /ml (CHR 1.71, p = 0.037). There is high early on- ART mortality in patients presenting with advanced immunodeficiency. Detecting cases and initiating ART before onset of advanced immunodeficiency might improve survival.

Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study.

PubMed

Van der Watt, Johan J; Wilkinson, Katalin A; Wilkinson, Robert J; Heckmann, Jeannine M

2014-02-10

In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study. One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays. Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002). The initiation of cART in previously treatment naïve individuals was associated with a cytokine

Subacute Sclerosing Panencephalitis in a Child Suffering from Human Immunodeficiency Virus on "Highly Active Antiretroviral Therapy" - Can This be Another Instance of Immune Reconstitution Inflammatory Syndrome?

PubMed

Gupta, Ashutosh; Kushwaha, Suman; Manzoor, Mushbiq; Tarfarosh, Shah Faisal Ahmad

2017-06-13

We report a 12-year-old boy with human immunodeficiency virus (HIV) who presented with rapidly progressive difficulty in ambulation. The symptoms started to worsen when he was put on antiretroviral therapy (ART). Our findings show that the dynamics of HIV-related immune suppression and highly active antiretroviral therapy (HAART) have an impact on the clinical course of Subacute sclerosing panencephalitis (SSPE). Slow progression is expected in children on HAART but in our case, we observe a complex interaction of the virus with the immune system and modification of disease course of SSPE with ART. The child we discuss in this case report developed rapidly progressive SSPE on HAART regime; so the possibility of SSPE to be labeled as immune reconstitution inflammatory syndrome (IRIS) should be considered.

Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

PubMed Central

Law, Matthew G; Achhra, Amit; Deeks, Steven G; Gazzard, Brian; Migueles, Stephen A; Novak, Richard M; Ristola, Matti

2014-01-01

Objectives A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined. Methods We assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomisation. The key covariables considered for this analysis were race, hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤50 and ≤400 copies/mL using logistic regression. Because of the strong association between region of randomisation and baseline low HIV RNA, analyses were stratified by region. Results We found that of 4676 eligible participants randomised in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher HDL levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA. Conclusion In a modern cohort of early untreated HIV infection we found that HIV exposure routes other than male homosexual contact and higher HDL were associated with increased odds of low HIV RNA. PMID:25711322

Risk factors for mortality in a south Indian population on generic antiretroviral therapy.

PubMed

Rupali, Priscilla; Mannam, Sam; Bella, Annie; John, Lydia; Rajkumar, S; Clarence, Peace; Pulimood, Susanne A; Samuel, Prasanna; Karthik, Rajiv; Abraham, Ooriapadickal Cherian; Mathai, Dilip

2012-12-01

Antiretroviral treatment (ART) programs from low-income countries utilizing standardized ART regimens, simplified approaches to clinical decision making and basic lab monitoring have reported high mortality rates. We determined the risk factors for mortality among HIV-infected adults following the initiation of ART from a single center in south India. ART-naive HIV-infected south Indian adults attending the Infectious Diseases clinic in a 2000-bed academic medical center in south India who were initiated on ART (generic, fixed-dose combinations) as per the national guidelines were followed up. Cases (32 patients who died) were compared with age and sex matched controls. Eight-hundred and twenty-two patients were started on ART from January 1, 2000 to December 31, 2008. The cumulative mortality was 6.8% (56/822). Among the cases mean age was 44 years, 18% were women and mean CD4 counts was 107 cells/microl. Among the controls mean age was 41 years, 18% were women and mean CD4 counts were 113 cells/microl. Stavudine based ART was predominant 62.5% in the cases vs 37.5% in the controls, followed by zidovudine based therapy in 31.2% of cases and 43.7% in the controls. Tenofovir based therapy was used in 6.2% of cases vs 18.7% in the controls. The commonest causes of death were drug toxicity 19%, advanced Acquired Immunodeficiency Syndrome (AIDS) in 37%, Immune Reconstitution Inflammatory Syndrome (IRIS) in 16%, non AIDS related deaths in 22% and malignancies 6%. In a univariate analysis, absolute lymphocyte count <1200 cells/cmm (p=0.03), development of immune reconstitution inflammatory syndrome (IRIS) (p=0.000) and mean CD4 cell count increase <75 cells/microl after 1 year of ART (p=0.001) were significantly associated with mortality. The mortality among our patients was comparable to that reported from other low-income countries. Earlier initiation of ART may reduce the high mortality rates observed.

Magnitude of Antiretroviral Drug Toxicity in Adult HIV Patients in Ethiopia: A cohort study at seven teaching hospitals.

PubMed

Gudina, Esayas Kebede; Teklu, Alula M; Berhan, Asres; Gebreegziabhier, Atsbeha; Seyoum, Teshome; Nega, Abiy; Medhin, Girmay; Kebede, Amha; Assefa, Yibeltal

2017-02-01

The introduction of antiretroviral therapy (ART) has resulted in significant mortality reduction and improvement in the quality of life. However, this has come at a cost of increased drug toxicity. The objective of this study was to assess the patterns and predictors of ART toxicity in adult HIV patients in Ethiopia. This is a prospective cohort study conducted at seven teaching hospitals between September 2009 and December 2013 involving 3921 HIV patients on ART. Adverse drug reactions (ADR) due to ART were identified based on clinical assessment and/or laboratory parameters. Multivariable random effects Poisson regression analysis was used to identify factors independently associated with toxicity. ADR due to ART drugs was reported in 867 (22.1 %) of the participants; 374 (9.5%) had severe forms. About 87% of reported toxicities were limited to three organ systems - the skin, nervous system and blood. The overall incidence of ADR was 9 per 100 person years. About a third of toxicities occurred during the first six months after ART initiation with the incidence rate of 22.4 per 100 person years. Concomitant anti-tuberculosis treatment was the strongest independent predictor of toxicity. ADR was found to be highly prevalent in HIV patients on ART at tertiary hospitals in Ethiopia. Most of these conditions occurred early after ART initiation and in those with concomitant anti-tuberculosis treatment. Thus, routine monitoring of patients on ART should be strengthened with particular emphasis in the first 6 months. Strategies should also be devised to replace older and more toxic agents with newer and safer drugs available.

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. © The Author(s) 2015.

Antiretroviral Resistance in HIV/AIDS Patients

NASA Astrophysics Data System (ADS)

Manosuthi, W.; MD

2018-03-01

The higher prevalence of HIV drug resistance was observed in areas with greater ART coverage. The HIV resistance-associated mutations occur when people have inadequate levels of antiretroviral drugs as well as inadequate potency, inadequate adherence, and preexisting resistance. The degree to drug cross-resistance is observed depends on the specific mutations and number of mutation accumulation. In the Southeast Asia region, the challenging of people with treatment failure is the availability and accessibility to subsequent new antiretroviral drugs to construct he second and salvage regimen. Genotypic resistance testing is a useful tool because it can identify the existing drug resistance-associated mutations under the selective drug pressure. Thus, understanding the basic interpretation of HIV drug resistance- associated mutation is useful in guiding clinical decisions for treatment-experienced people living with HIV.

Did Universal Access to ARVT in Mexico Impact Suboptimal Antiretroviral Prescriptions?

PubMed Central

Caro-Vega, Yanink; Sierra-Madero, Juan; Colchero, M. Arantxa; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio

2013-01-01

Background. Universal access to antiretroviral therapy (ARVT) started in Mexico in 2001; no evaluation of the features of ARVT prescriptions over time has been conducted. The aim of the study is to document trends in the quality of ARVT-prescription before and after universal access. Methods. We describe ARVT prescriptions before and after 2001 in three health facilities from the following subsystems: the Mexican Social Security (IMSS), the Ministry of Health (SSA), and National Institutes of Health (INS). Combinations of drugs and reasons for change were classified according to current Mexican guidelines and state-of-the-art therapy. Comparisons were made using χ 2 tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription. PMID:24396592

Better antiretroviral therapy outcomes at primary healthcare facilities: an evaluation of three tiers of ART services in four South African provinces.

PubMed

Fatti, Geoffrey; Grimwood, Ashraf; Bock, Peter

2010-09-21

There are conflicting reports of antiretroviral therapy (ART) effectiveness comparisons between primary healthcare (PHC) facilities and hospitals in low-income settings. This comparison has not been evaluated on a broad scale in South Africa. A retrospective cohort study was conducted including ART-naïve adults from 59 facilities in four provinces in South Africa, enrolled between 2004 and 2007. Kaplan-Meier estimates, competing-risks Cox regression, generalised estimating equation population-averaged models and logistic regression were used to compare death, loss to follow-up (LTFU) and virological suppression (VS) between PHC, district and regional hospitals. 29 203 adults from 47 PHC facilities, nine district hospitals and three regional hospitals were included. Patients at PHC facilities had more advanced WHO stage disease when starting ART. Retention in care was 80.1% (95% CI: 79.3%-80.8%), 71.5% (95% CI: 69.1%-73.8%) and 68.7% (95% CI: 67.0%-69.7%) at PHC, district and regional hospitals respectively, after 24 months of treatment (P<0.0001). In adjusted regression analyses, LTFU was independently increased at regional hospitals (aHR 2.19; 95% CI: 1.94-2.47) and mortality was independently elevated at district hospitals (aHR 1.60; 95% CI: 1.30-1.99) compared to PHC facilities after 12 months of ART. District and regional hospital patients had independently reduced probabilities of VS, aOR 0.76 (95% CI: 0.59-0.97) and 0.64 (95% CI: 0.56-0.75) respectively compared to PHC facilities over 24 months of treatment. ART outcomes were superior at PHC facilities, despite PHC patients having more advanced clinical stage disease when starting ART, suggesting that ART can be adequately provided at this level and supporting the South African government's call for rapid up-scaling of ART at the primary level of care. Further prospective research is required to determine the degree to which outcome differences are attributable to either facility level characteristics or

Joint power generation differentiates young and adult sprinters during the transition from block start into acceleration: a cross-sectional study.

PubMed

Debaere, Sofie; Vanwanseele, Benedicte; Delecluse, Christophe; Aerenhouts, Dirk; Hagman, Friso; Jonkers, Ilse

2017-11-01

The aim of this study was to investigate differences in joint power generation between well-trained adult athletes and young sprinters from block clearance to initial contact of second stance. Eleven under 16 (U16) and 18 under 18 (U18) promising sprinters executed an explosive start action. Fourteen well-trained adult sprinters completed the exact same protocol. All athletes were equipped with 74 spherical reflective markers, while an opto-electronic motion analysis system consisting of 12 infrared cameras (250 Hz, MX3, Vicon, Oxford Metrics, UK) and 2 Kistler force plates (1,000 Hz) was used to collect the three-dimensional marker trajectories and ground reaction forces (Nexus, Vicon). Three-dimensional kinematics, kinetics, and power were calculated (Opensim) and time normalised from the first action after gunshot until initial contact of second stance after block clearance. This study showed that adult athletes rely on higher knee power generation during the first stance to induce longer step length and therefore higher velocity. In younger athletes, power generation of hip was more dominant.

Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

PubMed Central

2009-01-01

Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART). Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment. PMID:19840392

Use of antiretroviral therapy in resource-limited countries in 2006: distribution and uptake of first- and second-line regimens.

PubMed

Renaud-Théry, Françoise; Nguimfack, Boniface Dongmo; Vitoria, Marco; Lee, Evan; Graaff, Peter; Samb, Badara; Perriëns, Joseph

2007-07-01

To address the information gap on current use of antiretroviral drugs (ARTs) in developing countries. The AIDS Medicines and Diagnostics Service of the World Health Organization (WHO) carried out a multi-country survey in early 2006. Questionnaires covered the use of first- and second-line regimens in adults and children, and the rates of switching from first-line to second-line regimen. Weighted percentages of use of ARTs across the cohort of adults and children were calculated and correlated with 2006 WHO guidelines. A second analysis compared demand for ARTs with rates of production of active pharmaceutical ingredients. Twenty-three countries (96%) returned the questionnaires, representing 53% of relevant patients in developing countries as of June 2006, and comprising 92% adults and 8% children receiving ARTs. Response rates were highest for questions regarding first-line use and lowest for those regarding pediatric regimens. The distribution of first-line: second-line use was 96%: 4% among adults and 99%: 1% among children. For adults, 95% of those receiving first-line treatment, but only 25% of those receiving second-line treatment, were on regimens consistent with those preferred by the WHO. Among first-line users, the most common regimen (61%) was stavudine+lamivudine+nevirapine. Among second-line users, abacavir+didanosine+lopinavir/ritonavir was the most common regimen (24%). Among children, compliance with WHO guidelines was high among the respondents, with zidovudine+lamivudine+nevirapine reported as the main option. Estimates of first-year switching rate were highly variable, ranging from 1% to 15%, with only ten responses. Comparison of supply and demand showed that the stated production capacity for active pharmaceutical ingredients is sufficient to meet current demands for ARTs. This survey has provided valuable information on the uptake of ARTs in developing countries and will help forecast future demand. Reporting for second-line and pediatric

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

PubMed

Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G; Henry, Keith; Jain, Mamta K; Palfreeman, Adrian; Mugyenyi, Peter; Domingo, Pere; Hoffmann, Christian; Read, Tim R H; Pujari, Sanjay; Meulbroek, Michael; Johnson, Margaret; Wilkin, Timothy; Mitsuyasu, Ronald

2016-12-15

 In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.  Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights

Antiretrovirals and safer conception for HIV-serodiscordant couples

PubMed Central

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

2013-01-01

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

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.

Reported consent processes and demographics: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

PubMed Central

Denning, Eileen; Sharma, Shweta; Smolskis, Mary; Touloumi, Giota; Walker, Sarah; Babiker, Abdel; Clewett, Megan; Emanuel, Ezekiel; Florence, Eric; Papadopoulos, Antonios; Sánchez, Adriana; Tavel, Jorge; Grady, Christine

2014-01-01

Objectives Efforts are needed to improve informed consent of participants in research. The Strategic Timing of AntiRetroviral Therapy (START) study provides a unique opportunity to study the effect of length and complexity of informed consent documents on understanding and satisfaction among geographically diverse participants. Methods Interested START sites were randomised to use either the standard consent form or the concise consent form for all of the site’s participants. Results A total of 4473 HIV-positive participants at 154 sites worldwide took part in the Informed Consent Substudy, with consent given in 11 primary languages. Most sites sent written information to potential participants in advance of clinic visits, usually including the consent form. At about half the sites, staff reported spending less than an hour per participant in the consent process. The vast majority of sites assessed participant understanding using informal nonspecific questions or clinical judgment. Conclusions These data reflect the interest of START research staff in evaluating the consent process and improving informed consent. The START Informed Consent Substudy is by far the largest study of informed consent intervention ever conducted. Its results have the potential to impact how consent forms are written around the world. PMID:25711320

Acceptability of Early Antiretroviral Therapy Among South African Women.

PubMed

Garrett, Nigel; Norman, Emily; Leask, Kerry; Naicker, Nivashnee; Asari, Villeshni; Majola, Nelisile; Karim, Quarraisha Abdool; Karim, Salim S Abdool

2018-03-01

WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272-1095) by 2015 (p < 0.001). Median viral load at ART initiation decreased over this period from 5.2 (IQR 4.6-5.6) to 4.1 (IQR 3.4-4.6) log copies/ml (p = 0.004). Virological suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.

When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa

PubMed Central

Schomaker, Michael; Egger, Matthias; Ndirangu, James; Phiri, Sam; Moultrie, Harry; Technau, Karl; Cox, Vivian; Giddy, Janet; Chimbetete, Cleophas; Wood, Robin; Gsponer, Thomas; Bolton Moore, Carolyn; Rabie, Helena; Eley, Brian; Muhe, Lulu; Penazzato, Martina; Essajee, Shaffiq; Keiser, Olivia; Davies, Mary-Ann

2013-01-01

Background There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%. Methods and Findings ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The

Antiretroviral therapy as HIV prevention: status and prospects.

PubMed

Mayer, Kenneth H; Venkatesh, Kartik K

2010-10-01

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.

High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo.

PubMed

Dagnra, Anoumou Y; Vidal, Nicole; Mensah, Akovi; Patassi, Akouda; Aho, Komi; Salou, Mounerou; Monleau, Marjorie; Prince-David, Mireille; Singo, Assétina; Pitche, Palokinam; Delaporte, Eric; Peeters, Martine

2011-06-10

With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. Our objective is to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization public health approach to monitor antiretroviral treatment (ART) in Togo. Patients on HAART for one year (10-14 months) were enrolled between April and October 2008 at three sites in Lomé, the capital city of Togo. Plasma viral load was measured with the NucliSENS EasyQ HIV-1 assay (Biomérieux, Lyon, France) and/or a Generic viral load assay (Biocentric, Bandol, France). Genotypic drug-resistance testing was performed with an inhouse assay on plasma samples from patients with viral loads of more than 1000 copies/ml. CD4 cell counts and demographic data were also obtained from medical records. A total of 188 patients receiving first-line antiretroviral treatment were enrolled, and 58 (30.8%) of them experienced virologic failure. Drug-resistance mutations were present in 46 patients, corresponding to 24.5% of all patients enrolled in the study. All 46 patients were resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTIs): of these, 12 were resistant only to NNRTIs, 25 to NNRTIs and lamivudine/emtricitabine, and eight to all three drugs of their ARV regimes. Importantly, eight patients were already predicted to be resistant to etravirine, the new NNRTI, and three patients harboured the K65R mutation, inducing major resistance to tenofovir. In Togo, efforts to provide access to ARV therapy for infected persons have increased since 2003, and scaling up of ART started in 2007. The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the

The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

PubMed

Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

2017-11-15

The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Understanding the facilitators and barriers of antiretroviral adherence in Peru: A qualitative study

PubMed Central

2010-01-01

Background Antiretroviral scale-up is increasing in resource-constrained settings. To date, few studies have explored the barriers and facilitators of adherence to ART in these settings. Facilitators and barriers of antiretroviral adherence in Peru are not completely understood. Methods At two clinics that serve a large number of HIV-positive individuals in Lima, Peru, 31 in-depth interviews were carried out in 2006 with adult HIV-positive individuals receiving ART. Purposive sampling was used to recruit the participants. Interviews were transcribed and coded using two Spanish-speaking researchers and a content analysis approach to identify themes in the data. Results Among the participants, 28/31 (90%) were male, 25/31 (81%) were self-identified as mestizo, and 19/31 (61%) had an education above high school. The most frequently discussed barriers to adherence included side effects, simply forgetting, inconvenience, dietary requirements, being away from home, and fear of disclosure/stigma. The most frequently discussed facilitators to adherence included having a fixed routine, understanding the need for compliance, seeing positive results, treatment knowledge, and faith in treatment. Conclusions Overall, these findings were similar to the facilitators and challenges experienced by individuals on ART in other resource constrained settings. Further treatment support tools and networks should be developed to decrease the challenges of ART adherence for HIV-positive individuals in Lima, Peru. PMID:20070889

Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

PubMed

Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

2002-06-13

Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (<37 weeks of gestation) was similar among the women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (<2500 g) was 16 percent among the infants born to both groups; and the rate of very low birth weight (<1500 g) was 2 percent for the group that received antiretroviral therapy and 1 percent for the group that did not. The rates of low Apgar scores (<7) and stillbirth were also similar or the same in the two groups. After adjustment for multiple risk factors, combination antiretroviral therapy was not associated with an increased risk of premature delivery as compared with monotherapy (odds ratio, 1.08; 95 percent confidence interval, 0.71 to 1.62) or delivery of an infant with low birth weight (odds ratio, 1.03; 95 percent confidence interval, 0.64 to 1.63). Seven of the women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy

Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet® International Outcome Study.

PubMed

Polak, Michel; Blair, Jo; Kotnik, Primoz; Pournara, Effie; Pedersen, Birgitte Tønnes; Rohrer, Tilman R

2017-11-01

To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD). NordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting. Patients ( n  = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8-10; boys, 9-11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS). Age at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early ( n  = 40 (boys, 70.0%); least squares mean (standard error) -0.76 (0.14)) exceeded that achieved by those starting later (intermediate, n  = 42 (boys, 57.1%); -1.14 (0.15); late, n  = 90 (boys, 68.9%); -1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start ( P  < 0.0242), baseline height SDS (HSDS) ( P  < 0.0001), target HSDS ( P  < 0.0001), and GHD severity ( P  = 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start. Early initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential. © 2017 The authors.

Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria

PubMed Central

Chang, Charlotte A.; Meloni, Seema Thakore; Eisen, Geoffrey; Chaplin, Beth; Akande, Patrick; Okonkwo, Prosper; Rawizza, Holly E.; Tchetgen Tchetgen, Eric; Kanki, Phyllis J.

2015-01-01

Background. Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods. This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results. Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7–27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4+ cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions. The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections. PMID:26613097

miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging.

PubMed

Zhan, Jiaxin; Qin, Shanshan; Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang

2016-11-26

Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging.

Antiretroviral Agents Effectively Block HIV Replication after Cell-to-Cell Transfer

PubMed Central

Permanyer, Marc; Ballana, Ester; Ruiz, Alba; Badia, Roger; Riveira-Munoz, Eva; Gonzalo, Encarna; Clotet, Bonaventura

2012-01-01

Cell-to-cell transmission of HIV has been proposed as a mechanism contributing to virus escape to the action of antiretrovirals and a mode of HIV persistence during antiretroviral therapy. Here, cocultures of infected HIV-1 cells with primary CD4+ T cells or lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals in cell-free virus infections and in vivo. PMID:22696642

Progress of the National Pediatric Free Antiretroviral Therapy program in China.

PubMed

Zhao, Yan; Sun, Xin; He, Yun; Tang, Zhirong; Peng, Guoping; Liu, Aiwen; Qiao, Xiaochun; Li, Huiqin; Chen, Zhiqiang; Dou, Zhihui; Ma, Ye; Liu, Zhongfu; Zhang, Fujie

2010-10-01

In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system.

Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

PubMed

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

2013-10-01

Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. 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. 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. Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea.

PubMed

Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar

2016-01-01

The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p < .001). Overall, 55% patients had low or insufficient adherence. CEAT-VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.

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.

Cognitive impairment and antiretroviral treatment in a Peruvian population of patients with human immunodeficiency virus.

PubMed

Guevara-Silva, E A

2014-05-01

HIV-associated cognitive impairment occurs even in the early stages of infection. Short-term memory, psychomotor speed, attention, and executive functioning are the main capacities affected. Controversy exists regarding whether highly active antiretroviral therapy (HAART) is helpful in combating this process. The objective of the present study is to determine the association between cognitive impairment and HAART in HIV-infected patients from Hospital Regional de Huacho. Prospective study of HIV patients meeting criteria to start HAART. Twenty-one HIV-positive patients were recruited between April and July 2011. Researchers administered a standardised neuropsychological test battery before and 4 weeks after onset of HAART. Psychomotor speed, executive function, short term memory (visual and verbal), attention, and visuospatial performance were evaluated. Nineteen patients completed the study (14 males and 5 females). In the pre-HAART evaluation, most patients scored below average on the executive function and psychomotor speed subtests. Psychomotor speed and immediate visual memory improved significantly after four months of treatment with HAART. Some degree of cognitive decline may present even in the early and asymptomatic stages of HIV infection. The benefits of antiretroviral treatment for cognitive performance can be detected after only a few weeks of follow-up. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Cross-sectional study of CD4: CD8 ratio recovery in young adults with perinatally acquired HIV-1 infection.

PubMed

Pollock, Katrina M; Pintilie, Hannah; Foster, Caroline; Fidler, Sarah

2018-02-01

Antiretroviral therapy (ART) has improved survival into adulthood for young people with perinatally acquired HIV-1 (yp-PaHIV), but long-term prognosis remains unclear. We hypothesized that on-going immune activation, reflected in the failure of CD4:CD8 ratio normalization would be observed in yp-PaHIV, despite ART.A cross-sectional study of routinely collected clinical data from a cohort of yp-PaHIV (≥16 years).Data were collected from records of individuals attending a specialist clinic for yp-PaHIV transitioning to adult care. CD4:CD8 ratio and proportion with CD4:CD8 ratio ≥1, demographic data and viral parameters, including HIV-1 viral load (VL) and human cytomegalovirus (CMV) IgG, were analyzed with IBM SPSS Statistics v22.A total of 115 yp-PaHIV, median (IQR) age 22.0 (20.0-24.0) years, were studied, of whom 59 were females, and the majority were Black African 75/115 (65.2%). Where measured, CMV antibodies were frequently detected (71/74, 95.9%) and CMV IgG titre was inversely associated with CD4:CD8 ratio, (Rho -0.383, P = .012). Of those taking ART, 69 out of 90 (76.7%) yp-PaHIV had suppressed HIV viremia (<50 RNA copies/mL) and recovery of CD4:CD8 ratio to ≥1 was seen in 26 out of 69 (37.7%) with suppressed HIV viremia. Persistence of low CD4:CD8 ratio was observed even in those with a CD4 count ≥500 cells/μL, where 28/52 (53.8%) had a CD4:CD8 ratio <1. Of those with suppressed viremia, the median (IQR) age for starting ART was 8.0 (5.0-12.8) years and CD4:CD8 ratio was inversely associated with age at ART start, Rho -0.348, (P = .028).In this cohort of yp-PaHIV, despite lifelong HIV infection and widespread CMV coinfection, CD4:CD8 ratio recovery rate was comparable to adults treated in acute infection. Where persistence of CD4:CD8 ratio abnormality was observed, on-going immune activation may have significance for non-AIDS outcomes. Taken together our findings indicate immune resilience to be a feature of these adult survivors of

Can the generic antiretroviral industry support access to a universal antiretroviral regimen?

PubMed

Amole, Carolyn D; Middlecote, Caroline; Prabhu, Vineet R; Kumarasamy, N

2017-07-01

The generic antiretroviral (ARV) industry played a critical role in the massive scale-up of HIV treatment in low-income and middle-income countries since 2000. As the global community looks ahead to a universal antiretroviral regimen, this article considers the industry's role in supporting universal access to affordable, simpler, more durable, and tolerable HIV treatment regimens. Generic manufacturers made treatment scale-up in low-income and middle-income countries possible through reducing prices, combining molecules from different originator companies to develop optimal fixed-dose combinations, and investing in production capacity to meet escalating demand. Achieving scale-up of a universal regimen will require continued partnership in these areas. Collaboration on the demand and supply sides of the ARV marketplace will be required to foster a healthy and sustainable marketplace for new regimens. This includes clear priority setting from the global treatment community on priority products; predictable demand; regulatory prioritization of optimal products; effective tendering and procurement practices that enable multiple suppliers to participate in the market; coordinated product introduction efforts between Ministries of Health, partners, and civil society; and transparency from both buyers and suppliers to promote and monitor supply security. New regimens will benefit people living with HIV, as well as buyers and generic suppliers, by maximizing existing production capacity and treatment budgets to reach the 90-90-90 goals.

[HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area].

PubMed

Zapiola, Inés; Cecchini, Diego; Fernández Giuliano, Silvina; Martínez, Marina; Rodríguez, Claudia; Bouzas, María Belén

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Oklahoma City FILM Even Start Family Literacy Program Evaluation, 2000-2001.

ERIC Educational Resources Information Center

Richardson, Donna Castle; Shove, Joanie; Brickman, Sharon; Terrell, Sherry; Shields, Jane

This report presents findings from the evaluation of the Oklahoma City Public Schools Even Start Program, also called the Family Intergenerational Literacy Model (FILM), now in its twelfth full year of operation. The evaluation focuses on the total population of adult students, preschoolers, adult graduates, and preschool graduates. The…

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

PubMed

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

2005-05-01

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

Determinants of weight evolution among HIV-positive patients initiating antiretroviral treatment in low resource settings

PubMed Central

Huis in ‘t Veld, D.; Balestre, E.; Buyze, J; Menten, J.; Jaquet, A.; Cooper, D.A.; Dabis, F.; Yiannoutsos, C. T.; Diero, L.; Mutevedzi, P.; Fox, M.P.; Messou, E.; Hoffmann, C.J.; Prozesky, H.W.; Egger, M.; Hemingway-Foday, J.J.; Colebunders, R.

2015-01-01

Background In resource limited settings clinical parameters, including body weight changes, are used to monitor clinical response. Therefore we studied body weight changes in patients on antiretroviral treatment (ART) in different regions of the world. Methods Data were extracted from the “International Epidemiologic Databases to Evaluate AIDS”, a network of ART programmes that prospectively collects routine clinical data. Adults on ART from the Southern-, East-, West- and Central African and the Asia-Pacific regions were selected from the database if baseline data on body weight, gender, ART regimen and CD4 count were available. Body weight change over the first two years and the probability of body weight loss in the second year were modelled using linear mixed models and logistic regression respectively. Results Data from 205,571 patients were analysed. Mean adjusted body weight change in the first 12 months was higher in patients started on tenofovir and/or efavirenz; in patients from Central, West and East Africa, in men, and in patients with a poorer clinical status. In the second year of ART it was greater in patients initiated on tenofovir and/or nevirapine, and for patients not on stavudine, in women, in Southern Africa and in patients with a better clinical status at initiation. Stavudine in the initial regimen was associated with a lower mean adjusted body weight change and with weight loss in the second treatment year. Conclusion Different ART regimens have different effects on body weight change. Body weight loss after one year of treatment in patients on stavudine might be associated with lipoatrophy. PMID:26375465

Optimising research to speed up availability of paediatric antiretroviral drugs and formulations

PubMed Central

Penazzato, M; Gnanashanmugam, D; Rojo, P; Lallemant, M; Lewis, L; Rocchi, F; Saint Raymond, A; Ford, N; Hazra, R; Giaquinto, C; Gibb, D; Abrams, Elaine J

2018-01-01

Globally 1.8 million children are estimated to be living with HIV, yet only 51% of those eligible actually start treatment. The completion of research and development (R&D) for paediatric antiretrovirals (ARVs) is a lengthy process and licensing of new paediatric ARVs continues to lag considerably behind adults. Providing safe, effective, and well-tolerated drugs for children remains critical to ensuring scale-up of paediatric treatment globally. In this manuscript we review current approaches to R&D for paediatric ARVs and suggest innovations to enable simplified, faster, and more comprehensive strategies to develop optimal formulations. Several approaches could be adopted, including enrolment of multiple age-cohorts concurrently and the early introduction of dosing approaches for both single and fixed-dose combination (FDC) drug formulations (preferably scored and dispersible) that match WHO weight-bands. Efforts to speed up development of optimal drugs and formulations for children should focus on a limited number of prioritised formulations. This work should build upon existing partnerships and collaborations to ensure that paediatric investigation plans are developed early in the drug development process but can be modified in a streamlined manner as more information becomes available. In addition, simplified and more efficient mechanisms to undertake R&D need to be put in place, and financing mechanisms must be made more efficient and sustainable. Registration, implementation, and strategic use of drugs should not be seen as a sequential process, with research designed to address multiple questions simultaneously to respond to the needs of HIV-infected children where they live. It is imperative that lessons learned from HIV should be shared to support progress in developing paediatric formulations for other diseases with similar treatment challenges, including tuberculosis and viral hepatitis. PMID:29190337

Initiation of highly active antiretroviral therapy among pregnant women in Cape Town, South Africa.

PubMed

Stinson, Kathryn; Boulle, Andrew; Coetzee, David; Abrams, Elaine J; Myer, Landon

2010-07-01

To investigate highly active antiretroviral therapy (HAART) initiation among pregnant women and the optimum model of service delivery for integrating HAART services into antenatal care. We analysed clinic records to reconstruct a cohort of all HIV-infected pregnant women eligible for HAART at four antenatal clinics representing three service delivery models in Cape Town, South Africa. To assess HAART coverage, records of women determined to be eligible for HAART in pregnancy were reviewed at corresponding HIV treatment services. Of 13,208 pregnant women tested for HIV, 26% were HIV-infected and 15% were HAART-eligible based on a CD4 cell count of antiretroviral intervention before delivery. The proportions of women initiating HAART between the different service delivery models were comparable. The median gestational age at first presentation was 26 weeks, and early gestational age at first presentation was the strongest predictor of being on HAART by delivery. Of the women who did not initiate HAART in pregnancy, 24% started treatment within 2 years postpartum. In this setting with clear PMTCT and HAART protocols, services failed to prioritize and initiate a high proportion of eligible pregnant women on HAART. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.

Antiretroviral therapy for human immunodeficiency virus infection in 1997.

PubMed Central

Katzenstein, D A

1997-01-01

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection. PMID:9217434

Increased soluble vascular cell adhesion molecule-1 plasma levels and soluble intercellular adhesion molecule-1 during antiretroviral therapy interruption and retention of elevated soluble vascular cellular adhesion molecule-1 levels following resumption of antiretroviral therapy.

PubMed

Papasavvas, Emmanouil; Azzoni, Livio; Pistilli, Maxwell; Hancock, Aidan; Reynolds, Griffin; Gallo, Cecile; Ondercin, Joe; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

2008-06-19

We investigated the effect of short viremic episodes on soluble markers associated with endothelial stress and cardiovascular disease risk in chronically HIV-1-infected patients followed during continuous antiretroviral therapy, antiretroviral therapy interruption and antiretroviral therapy resumption. We assessed changes in plasma levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 by enzyme-linked immunosorbent assay, as well as T-cell activation (CD8+/CD38+, CD8+/HLA-DR+ and CD3+/CD95+) by flow cytometry, in 36 chronically HIV-1-infected patients participating in a randomized study. Patients were divided into the following three groups: a, on continuous antiretroviral therapy; b, on a 6-week antiretroviral therapy interruption; or c, on antiretroviral therapy interruption extended to the achievement of viral set point. Although all measurements remained stable over a 40-week follow-up on antiretroviral therapy, plasma levels of soluble vascular cell adhesion molecule-1 (P < 0.0001) and soluble intercellular adhesion molecule-1 (P = 0.003) increased during treatment interruption in correlation with viral rebound and T-cell activation. No significant changes in von Willebrand factor were observed in any of the groups. After resuming antiretroviral therapy, soluble vascular cell adhesion molecule-1 levels remained elevated even after achievement of viral suppression to less than 50 copies/ml. The prompt rise in plasma soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 upon viral rebound suggests an acute increase in endothelial stress upon treatment interruption, which may persists after viral resuppression of virus. Thus, viral replication during short-term treatment interruption may increase the overall cardiovascular risk during and beyond treatment interruption.

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

Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

PubMed

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

2009-06-29

It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with

Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use

PubMed Central

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B.; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L.; Dieckhaus, Kevin; Rosen, Marc I.; Kozal, Michael J.

2009-01-01

Background It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Methodology/Principal Findings Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004–2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85–5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5–74.3, p = 0.0016). Conclusions/Significance Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional

Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.

PubMed

Ogedengbe, O O; Naidu, E C S; Akang, E N; Offor, U; Onanuga, I O; Peter, A I; Jegede, A I; Azu, O O

2018-04-14

The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture. © 2018 American Society of Andrology and European Academy of Andrology.

[Antiretroviral treatment for HIV infection. Where we are and where we are going?].

PubMed

Sierra-Madero, Juan G; Franco-San-Sebastián, Dennise

2004-01-01

Antiretroviral treatment for HIV infection has evolved importantly during the last few years. Eradication of HIV is currently not a realistic target of antiretroviral therapy; however, long term virologic control is possible with current antiviral combinations in the majority of patients. This has resulted in a dramatic reduction in complications and mortality associated with AIDS, even though significant challenges remain. Some of them are the limited access to antiretroviral drugs that exist in most of the affected countries because of the elevated costs of the drugs, the high level of adherence needed for efficacy and the short term and long term toxicity. It is important that antiretroviral access programs financed with public funds consider the following points in their design: specialized prescription that optimizes the use of these resources, integration of prevention to care, evaluation of costs in a global perspective, and integration of research with medical care.

Blockade of the spinal BDNF-activated JNK pathway prevents the development of antiretroviral-induced neuropathic pain.

PubMed

Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

2016-06-01

Although antiretroviral agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. The antiretroviral toxic neuropathy induces debilitating and extremely difficult to treat pain syndromes that often lead to discontinuation of antiretroviral therapy. Due to the critical need for the identification of novel therapeutic targets to improve antiretroviral neuropathic pain management, we investigated the role of the JNK signalling pathway in the mechanism of antiretroviral painful neuropathy. Mice were exposed to zalcitabine (2',3'-dideoxycytidine, ddC) and stavudine (2',3'-didehydro-3'-deoxythymidine, d4T) that induced a persistent mechanical allodynia and a transient cold allodynia. Treatment with the JNK blocker SP600125 before antiretroviral administration abolished mechanical hypersensitivity with no effect on thermal response. A robust spinal JNK overphosphorylation was observed on post-injection day 1 and 3, along with a JNK-dependent increase in p-c-Jun and ATF3 protein levels. Co-immunoprecipitation experiments showed the presence of a heterodimeric complex between ATF3 and c-Jun indicating that these transcription factors can act together to regulate transcription through heterodimerization. A rise in BDNF and caspase-3 protein levels was detected on day 1 and BDNF sequestration prevented both caspase-3 and p-JNK increase. These data suggest that BDNF plays a role in the early stages of ddC-induced allodynia by promoting apoptotic events and the activation of a hypernociceptive JNK-mediated pathway. We illustrated the activation of a BDNF-mediated JNK pathway involved in the early events responsible for the promotion of neuropathic pain, leading to a better knowledge of the mechanisms involved in the antiretroviral neuropathy. JNK blockade prevents antiretroviral-induced pain hypersensitivity. This may represent a potential prophylactic treatment of neuropathic pain to improve antiretroviral

Using age-specific mortality of HIV infected persons to predict anti-retroviral treatment need: a comparative analysis of data from five African population-based cohort studies.

PubMed

Zaba, Basia; Kasamba, Ivan; Floyd, Sian; Isingo, Raphael; Herbst, Kobus; Bärnighausen, Till; Gregson, Simon; Nyamukapa, Constance; Kayuni, Ndoliwe; Todd, Jim; Marston, Milly; Wringe, Alison

2012-08-01

To present a simple method for estimating population-level anti-retroviral therapy (ART) need that does not rely on knowledge of past HIV incidence. A new approach to estimating ART need is developed based on calculating age-specific proportions of HIV-infected adults expected to die within a fixed number of years in the absence of treatment. Mortality data for HIV-infected adults in the pre-treatment era from five African HIV cohort studies were combined to construct a life table, starting at age 15, smoothed with a Weibull model. Assuming that ART should be made available to anyone expected to die within 3 years, conditional 3-year survival probabilities were computed to represent proportions needing ART. The build-up of ART need in a successful programme continuously recruiting infected adults into treatment as they age to within 3 years of expected death was represented by annually extending the conditional survival range. The Weibull model: survival probability in the infected state from age 15 = exp(-0.0073 × (age - 15)(1.69)) fitted the pooled age-specific mortality data very closely. Initial treatment need for infected persons increased rapidly with age, from 15% at age 20-24 to 32% at age 40-44 and 42% at age 60-64. Overall need in the treatment of naïve population was 24%, doubling within 5 years in a programme continually recruiting patients entering the high-risk period for dying. A reasonable projection of treatment need in an ART naive population can be made based on the age and gender profile of HIV-infected people. © 2012 Blackwell Publishing Ltd.

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.

Imported acquired immunodeficiency syndrome-related histoplasmosis in metropolitan France: a comparison of pre-highly active anti-retroviral therapy and highly active anti-retroviral therapy eras.

PubMed

Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

2011-11-01

Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome-related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985-1994) and HAART (1997-2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome-related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era.

Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi.

PubMed

Tenthani, Lyson; Haas, Andreas D; Tweya, Hannock; Jahn, Andreas; van Oosterhout, Joep J; Chimbwandira, Frank; Chirwa, Zengani; Ng'ambi, Wingston; Bakali, Alan; Phiri, Sam; Myer, Landon; Valeri, Fabio; Zwahlen, Marcel; Wandeler, Gilles; Keiser, Olivia

2014-02-20

To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi. We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21,939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11,534). Of the women who started ART under Option B+ (n = 21,939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%. Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.

Potential drug interactions in patients given antiretroviral therapy.

PubMed

Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-11-21

to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral

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

The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic.

PubMed

Broder, Samuel

2010-01-01

In the last 25 years, HIV-1, the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), has gone from being an "inherently untreatable" infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including (1) the life-long duration of therapy; (2) the ultimate role of pre-exposure prophylaxis (PrEP); (3) the cardiometabolic side-effects or other toxicities of long-term therapy; (4) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); (5) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and (6) the continued pace of new HIV-1

The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic

PubMed Central

Broder, Samuel

2010-01-01

In the last 25 years, HIV-1, the retrovirus responsible for the Acquired Immunodeficiency Syndrome (AIDS), has gone from being an “inherently untreatable” infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir® (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including 1.) the life-long duration of therapy; 2.) the ultimate role of pre-exposure prophylaxis (PrEP); 3.) the cardiometabolic side effects or other toxicities of long-term therapy; 4.) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); 5.) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and 6.) the continued pace of new HIV-1

[GeSIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2014)].

PubMed

2014-01-01

This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: <350cells/μL, A-I; 350-500 cells/μL, A-II, and >500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2

Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease

PubMed Central

Bayoumi, Ahmed M.; Barnett, Paul G.; Joyce, Vilija R.; Griffin, Susan C.; Sun, Huiying; Bansback, Nick J.; Holodniy, Mark; Sanders, Gillian; Brown, Sheldon T.; Kyriakides, Tassos C.; Angus, Brian; Cameron, D. William; Anis, Aslam H.; Sculpher, Mark; Owens, Douglas K.

2014-01-01

Objective Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease. Design We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. PMID:24129369

The Impact of a Community-Based Intervention Including a Monthly Food Ration on Food Insecurity Among HIV-Positive Adults During the First Year of Antiretroviral Therapy.

PubMed

Rothman, Jessica; Kayigamba, Felix; Hills, Victoria; Gupta, Neil; Machara, Faustin; Niyigena, Peter; Franke, Molly F

2018-01-01

The objective of this study was to examine how food insecurity changed among HIV-positive adults during the first 12 months of combination antiretroviral therapy (cART) and whether any change differed according to the receipt of food support, which was provided in the context of a comprehensive community-based intervention. We conducted secondary data analyses of data from a prospective cohort study of the effectiveness of a community-based cART delivery model when added to clinic-based cART delivery in Rwanda. We included patients from four health centers that implemented a clinic-based cART delivery model alone and five health centers that additionally implemented the intervention, which included 10 months of food support. We compared food insecurity at 3, 6, and 12 months, relative to baseline, and stratified by receipt of the intervention. Relative to baseline, median food insecurity score decreased after 3, 6, and 12 months (p value <0.0001 for all) for patients receiving a food ration through the community-based model for cART delivery. Among patients receiving care under the clinic-based cART model, food insecurity scores remained unchanged at 3 and 12 months and were significantly higher after 6 months. In adjusted analyses, participants enrolled in the community-based intervention with a food ration had a lower risk of severe food insecurity and a lower risk of moderate or severe food insecurity after 12 months. A comprehensive community-based HIV program including a food ration likely contributes to an alleviation of food insecurity among adults newly initiating cART.

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…

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

PubMed Central

Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peñaloza, Cristina; Rugeles, Maria T

2009-01-01

Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these

Human resources requirements for highly active antiretroviral therapy scale-up in Malawi.

PubMed

Muula, Adamson S; Chipeta, John; Siziya, Seter; Rudatsikira, Emmanuel; Mataya, Ronald H; Kataika, Edward

2007-12-19

Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and distribution of health professionals. We obtained data on the total number of patients on highly active antiretroviral treatment program from the Malawi National AIDS Commission and Ministry of Health, HIV Unit, and the number of registered health professionals from the relevant regulatory bodies. We also estimated number of health professionals required to deliver highly active antiretroviral therapy (HAART) using estimates of human resources from the literature. We also obtained data from the Ministry of Health on the actual number of nurses, clinical officers and medical doctors providing services in HAART clinics. We then made comparisons between the human resources situation on the ground and the theoretical estimates based on explicit assumptions. There were 610 clinicians (396 clinical officers and 214 physicians), 44 pharmacists and 98 pharmacy technicians and 7264 nurses registered in Malawi. At the end of March 2007 there were 85 clinical officer and physician full-time equivalents (FTEs) and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used for the delivery of HAART comprised 13.9% of all clinical officers and physicians and 1.1% of all nurses. Using the estimated numbers of health professionals from the literature required 15.7-31.4% of all physicians and clinical officers, 66.5-199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the available nurses. To provide HAART to all the 170,000 HIV infected persons estimated as clinically eligible would require 4.7% to 16.4% of the total number of nurses, 118.1% to 354.2% of all the available pharmacists and

Lipid-based nutrient supplements containing vitamins and minerals attenuate renal electrolyte loss in HIV/AIDS patients starting antiretroviral therapy: A randomized controlled trial in Zambia.

PubMed

Munkombwe, D; Muungo, T L; Michelo, C; Kelly, P; Chirwa, S; Filteau, S

2016-06-01

Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0

Threshold virus dynamics with impulsive antiretroviral drug effects

PubMed Central

Lou, Jie; Lou, Yijun; Wu, Jianhong

2013-01-01

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible. PMID:21987085

Transition of HIV-infected youths from paediatric to adult care, a Swedish single-centre experience.

PubMed

Westling, Katarina; Navér, Lars; Vesterbacka, Jan; Belfrage, Erik

2016-01-01

Transition of HIV-infected adolescents from paediatric care to adult care is vulnerable and entails a risk of treatment failure. Therefore, a Transitional Outpatient Clinic for HIV-infected adolescents and young adults was started in 2008. The aims were to describe the transition process and treatment results in a Swedish cohort of adolescents with HIV. A cross-sectional study of the adolescent and young adults with HIV at the clinic was performed in October 2013 and a 2-year follow-up at the end of 2015. The 34 patients in care in October 2013 were a median of 19 years, 50% were female. Thirty-one out of 34 (91%) were perinatally infected. In 2013, 88% were on antiretroviral treatment (ART), for a median duration of 9 years, 74% were on a protease inhibitor-based regimen. Twenty-nine patients were followed-up at the end of 2015. Twenty-three were transferred to the Infectious Disease Clinic and the median age for transition was 19 years. At the end of 2015, 90% were treated with ART and 61% had an integrase inhibitor-based treatment. Of those treated with ART for more than 6 months, 90% (2013) and 96% (2015) had a viral load < 50 HIV RNA copies/mL, despite resistance problems and complicating social factors. These figures were higher than reported in other studies and similar to the treatment results in the adult HIV population in Sweden. The present study showed that it is possible to achieve good treatment results in adolescents with HIV.

Interventions to improve antiretroviral therapy adherence among adolescents in low- and middle-income countries: A systematic review of the literature

PubMed Central

Dulli, Lisa S.; Murray, Kate R.; Silverstein, Hannah; Dal Santo, Leila; Olsen, Patrick; Darrow de Mora, Danielle; McCarraher, Donna R.

2018-01-01

Introduction Globally, an estimated 30% of new HIV infections occur among adolescents (15–24 years), most of whom reside in sub-Saharan Africa. Moreover, HIV-related mortality increased by 50% between 2005 and 2012 for adolescents 10–19 years while it decreased by 30% for all other age groups. Efforts to achieve and maintain optimal adherence to antiretroviral therapy are essential to ensuring viral suppression, good long-term health outcomes, and survival for young people. Evidence-based strategies to improve adherence among adolescents living with HIV are therefore a critical part of the response to the epidemic. Methods We conducted a systematic review of the peer-reviewed and grey literature published between 2010 and 2015 to identify interventions designed to improve antiretroviral adherence among adults and adolescents in low- and middle-income countries. We systematically searched PubMed, Web of Science, Popline, the AIDSFree Resource Library, and the USAID Development Experience Clearinghouse to identify relevant publications and used the NIH NHLBI Quality Assessment Tools to assess the quality and risk of bias of each study. Results and discussion We identified 52 peer-reviewed journal articles describing 51 distinct interventions out of a total of 13,429 potentially relevant publications. Forty-three interventions were conducted among adults, six included adults and adolescents, and two were conducted among adolescents only. All studies were conducted in low- and middle-income countries, most of these (n = 32) in sub-Saharan Africa. Individual or group adherence counseling (n = 12), mobile health (mHealth) interventions (n = 13), and community- and home-based care (n = 12) were the most common types of interventions reported. Methodological challenges plagued many studies, limiting the strength of the available evidence. However, task shifting, community-based adherence support, mHealth platforms, and group adherence counseling emerged as strategies

Trends in Loss to Follow-Up among Migrant Workers on Antiretroviral Therapy in a Community Cohort in Lesotho

PubMed Central

Bygrave, Helen; Kranzer, Katharina; Hilderbrand, Katherine; Whittall, Jonathan; Jouquet, Guillaume; Goemaere, Eric; Vlahakis, Nathalie; Triviño, Laura; Makakole, Lipontso; Ford, Nathan

2010-01-01

Background The provision of antiretroviral therapy (ART) to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. Design All adult patients (≥18 years) initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. Results Our cohort comprised 1185 people, among whom 12% (148) were migrant workers. Among the migrant workers, median age was 36.1 (29.6–45.9) and the majority (55%) were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15–6.73); between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18–4.73), whereas after 1 year the rate was 6.69 times greater (95%CI 3.18–14.09). Conclusions Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations. PMID:20976289

Antiretroviral therapy status among people who died of AIDS-related causes from 2009 to 2013 in Brazil: a population-based study.

PubMed

de Freitas, Marcelo Araújo; Miranda, Angélica Espinosa; Pascom, Ana Roberta Pati; de Oliveira, Silvano Barbosa; Mesquita, Fabio; Ford, Nathan

2016-11-01

To describe the antiretroviral therapy status of people living with HIV (PLHIV) who died of AIDS-related causes between 2009 and 2013. We conducted a cross-sectional, population-based study. Data were obtained by linking the mortality information system and the national ART dispensing database. Trends were modelled using linear regression analysis. A total of 61 425 AIDS-related deaths were registered in Brazil between 2009 and 2013. Median age at death was 41 years (IQR: 33-49), and 65.7% (40 337) of deaths were among men; 47.2% (29 004) of PLHIV who died during the study period had never started treatment, 7.0% (4274) had discontinued it, 15.9% (9775) were on ART for 6 months or less and 29.9% (18 372) were on ART for more than 6 months. Only 1.3% of PLHIV were on third-line ARV regimens when they died. AIDS-related mortality remains a challenge even in a context of sustained universal access to antiretroviral treatment due to failure of service provision, not to therapy failure. Robust health policies closing gaps in the HIV continuum of care are crucial to further reduce mortality. © 2016 John Wiley & Sons Ltd.

Impact of Antiretroviral Regimens on CSF Viral Escape in a Prospective Multicohort Study of ART-Experienced HIV-1 Infected Adults in the United States.

PubMed

Mukerji, Shibani S; Misra, Vikas; Lorenz, David R; Uno, Hajime; Morgello, Susan; Franklin, Donald; Ellis, Ronald J; Letendre, Scott; Gabuzda, Dana

2018-04-03

Cerebrospinal fluid (CSF) viral escape occurs in 4-20% of HIV-infected adults, yet the impact of antiretroviral therapy (ART) on CSF escape is unclear. Prospective study of 1063 participants with baseline plasma viral load (VL) ≤400 copies/ml between 2005-2016. Odds ratio for ART regimens (PI with nucleoside reverse transcriptase inhibitor [PI+NRTI] versus other ART) and CSF escape was estimated using mixed-effects models. Drug resistance mutation frequencies were calculated. Baseline mean age was 46, median plasma VL, CD4 nadir, and CD4 count were 50 copies/mL, 88 cells/μL, and 424 cells/μL, respectively; 48% on PI+NRTI, 33% on non-NRTI, and 6% on integrase inhibitors. During median follow-up of 4.4 years, CSF escape occurred in 77 participants (7.2%). PI+NRTI use was an independent predictor of CSF escape (OR 3.1 [95% CI 1.8-5.0]) in adjusted analyses and models restricted to plasma VL ≤50 copies/ml (p<0.001). Regimens containing atazanavir (ATV) were a stronger predictor of CSF viral escape than non-ATV PI+NRTI regimens. Plasma and CSF M184V/I combined with thymidine-analog mutations were more frequent in CSF escape versus no escape (23% vs. 2.3%). Genotypic susceptibility score-adjusted CNS penetration-effectiveness (CPE) values were calculated for CSF escape with M184V/I mutations (n=34). Adjusted CPE values were low (<5) for CSF and plasma in 27 (79%) and 13 (38%), respectively, indicating suboptimal CNS drug availability. PI+NRTI regimens are independent predictors of CSF escape in HIV-infected adults. Reduced CNS ART bioavailability may predispose to CSF escape in patients with M184V/I mutations. Optimizing ART regimens may reduce risk of CSF escape.

Use of Highly Active Antiretroviral Therapy in a Cohort of HIV-Seropositive Women

PubMed Central

Cook, Judith A.; Cohen, Mardge H.; Grey, Dennis; Kirstein, Lynn; Burke, Jane; Anastos, Kathryn; Palacio, Herminia; Richardson, Jean; Wilson, Tracey E.; Young, Mary

2002-01-01

Objectives. This study examined longitudinal trends in use of highly active antiretroviral therapy (HAART) among a cohort of HIV-positive participants in the Women's Interagency HIV Study. Methods. Beginning in 1994, 1690 HIV-positive women reported detailed information about their use of antiretroviral therapy at 6-month study visits. Multivariate logistic and Cox regression analyses were used to estimate the likelihood of antiretroviral therapy and HAART use among women with study visits preceding and following HAART availability. Results. Before the availability of HAART, the cohort's likelihood of any antiretroviral therapy use was associated with clinical indicators (CD4 count, viral load, symptom presence) as well as behavioral factors (abstaining from drug and alcohol use, participating in clinical trials). After HAART became commercially available, newly emerging predictors included college education, private insurance, absence of injection drug use history, and not being African American. Conclusions. After the penetration of HAART into this cohort, additional differences emerged between HAART users and nonusers. These findings can inform public health efforts to enhance women's access to the most effective types of therapy. PMID:11772767

Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults

PubMed Central

Mave, Vidya; Erlandson, Kristine M.; Gupte, Nikhil; Balagopal, Ashwin; Asmuth, David M.; Campbell, Thomas B.; Smeaton, Laura; Kumarasamy, Nagalingeswaran; Hakim, James; Santos, Breno; Riviere, Cynthia; Hosseinipour, Mina C.; Sugandhavesa, Patcharaphan; Infante, Rosa; Pillay, Sandy; Cardoso, Sandra W.; Tripathy, Srikanth; Mwelase, Noluthando; Berendes, Sima; Andrade, Bruno B.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

2016-01-01

Background. Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown. Methods. Among a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models. Results. Of 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P = .01), and the decreases in both CRP (P = .01) and interleukin 18 (P = .02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10 increase in soluble CD14 level (P = .05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P = .001). Conclusions. Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation. PMID:26962236

Antiretroviral Therapy-Induced Mitochondrial Toxicity: Potential Mechanisms Beyond Polymerase-γ Inhibition

PubMed Central

Selvaraj, Shanmugapriya; Ghebremichael, Musie; Li, Min; Foli, Yram; Langs-Barlow, Allison; Ogbuagu, Arit; Barakat, Lydia; Tubridy, Elizabeth; Edifor, Regina; Lam, Wing; Cheng, Yung-Chi; Paintsil, Elijah

2014-01-01

We hypothesized that competition between NRTI-triphosphate and endogenous deoxyribonucleoside triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of Pol-γ inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median RN pool was 10062 (IQR, 7090 – 12590), 4360 (IQR, 3058 –6838), and 2968 (IQR, 2538 – 4436) pmol/106 cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mtDNA copy number compared to negative controls (p<0.05). Cases had significantly higher expression of Pol-γ, nucleoside transporters, cellular kinases, and ABC compared to controls. Antiretroviral therapy perturbs ribonucleotide and deoxyribonucleotide pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of Pol-γ inhibition. PMID:24637942

Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa.

PubMed

Koethe, John R; Blevins, Meridith; Bosire, Claire; Nyirenda, Christopher; Kabagambe, Edmond K; Mwango, Albert; Kasongo, Webster; Zulu, Isaac; Shepherd, Bryan E; Heimburger, Douglas C

2013-03-01

Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression. A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models. A public-sector HIV clinic in Lusaka, Zambia. One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl. Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported. Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted.

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

PubMed

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

2015-01-02

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

Sexual risk taking among patients on antiretroviral therapy in an urban informal settlement in Kenya: a cross-sectional survey.

PubMed

Ragnarsson, Anders; Ekström, Anna Mia; Carter, Jane; Ilako, Festus; Lukhwaro, Abigail; Marrone, Gaetano; Thorson, Anna

2011-04-18

Our intention was to analyze demographic and contextual factors associated with sexual risk taking among HIV-infected patients on antiretroviral treatment (ART) in Africa's largest informal urban settlement, Kibera in Nairobi, Kenya. We used a cross-sectional survey in a resource-poor, urban informal settlement in Nairobi; 515 consecutive adult patients on ART attending the African Medical and Research Foundation clinic in Kibera in Nairobi were included in the study. Interviewers used structured questionnaires covering socio-demographic characteristics, time on ART, number of sexual partners during the previous six months and consistency of condom use. Twenty-eight percent of patients reported inconsistent condom use. Female patients were significantly more likely than men to report inconsistent condom use (aOR 3.03; 95% CI 1.60-5.72). Shorter time on ART was significantly associated with inconsistent condom use. Multiple sexual partners were more common among married men than among married women (adjusted OR 4.38; 95% CI 1.82-10.51). Inconsistent condom use was especially common among women and patients who had recently started ART, i.e., when the risk of HIV transmission is higher. Having multiple partners was quite common, especially among married men, with the potential of creating sexual networks and an increased risk of HIV transmission. ART needs to be accompanied by other preventive interventions to reduce the risk of new HIV infections among sero-discordant couples and to increase overall community effectiveness.

Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m(2).

PubMed

Pottel, Hans; Hoste, Liesbeth; Delanaye, Pierre

2015-05-01

The chronic kidney disease (CKD) classification system for children is similar to that for adults, with both mainly based on estimated glomerular filtration rate (eGFR) combined with fixed cut-off values. The main cut-off eGFR value used to define CKD is 60 mL/min/1.73 m(2), a value that is also applied for children older than 2 years of age, adolescents and young adults. Based on a literature search, we evaluated inclusion criteria for eGFR in clinical trials or research studies on CKD for children. We also collected information on direct measurements of GFR (mGFR) in children and adolescents, with the aim to estimate the normal reference range for GFR. Using serum creatinine (Scr) normal reference values and Scr-based eGFR-equations, we also evaluated the correspondence between Scr normal reference values and (e)GFR normal reference values. Based on our literature search, the inclusion of children in published CKD studies has been based on cut-off values for eGFR of >60 mL/min/1.73 m(2). The lower reference limits for mGFR far exceed this adult threshold. Using eGFR values calculated using Scr-based formulas, we found that abnormal Scr levels in children already correspond to eGFR values that are below a cut-off of 75 mL/min/1.73 m(2). Abnormal GFR in children, adolescents and young adults starts below 75 mL/min/1.73 m(2), and as abnormality is a sign of disease, we recommend referring children, adolescents and young adults with an (e)GFR of <75 mL/min/1.73 m(2) for further clinical assessment.

Neutropenia in HIV-Infected Kenyan Women Receiving Triple Antiretroviral Prophylaxis to Prevent Mother-to-Child HIV Transmission Is Not Associated with Serious Clinical Sequelae.

PubMed

Iuliano, A Danielle; Weidle, Paul J; Brooks, John T; Masaba, Rose; Girde, Sonali; Ndivo, Richard; Ogindo, Paul; Omolo, Paul; Zeh, Clement; Thomas, Timothy K

2015-01-01

Absolute neutrophil counts (ANCs) are lower in East African adults. To assess the impact of lower ANCs, we reviewed data from HIV-infected Kenyan women receiving antiretroviral therapy antepartum and postpartum. The Kisumu Breastfeeding Study (KiBS) participants received an antiretroviral regimen from 34 weeks' gestation through 6 months postpartum. Measured ANCs and subsequent illnesses were reviewed. Adverse events (AEs) potentially attributable to neutropenia were identified, and ANCs were graded using the 2004 Division of AIDS table for Grading the Severity of AEs. Among 478 women with ≥1 postpartum ANC measured, 298 (62.1%) women met criteria for an AE (<1.3 × 10(9) cells/L). Of those, 38 (12.5%) women experienced a nonlife-threatening illness potentially attributable to neutropenia. More than half of KiBS women met criteria for neutropenia. The mild clinical experience of most participants with low ANCs supports that these values might be typical for this population and may not result in adverse clinical sequelae. © The Author(s) 2013.

Vitamin D Deficiency in HIV-Infected Women on Antiretroviral Therapy Living in the Tropics.

PubMed

Conrado, Tereza; Miranda-Filho, Demócrito de Barros; Ximenes, Ricardo Arraes de Alencar; Albuquerque, Maria de Fátima; Lacerda, Heloísa Ramos; Ramos, Regina Coeli F; Araújo, Paulo Sérgio Ramos de; Montarroyos, Ulisses; Bandeira, Francisco

2011-01-01

The effects of HIV/AIDS and antiretroviral drugs on vitamin D metabolism are still mostly unknown. This was a cross-sectional study to estimate the prevalence of vitamin D deficiency and identify its association with the clinical and metabolic parameters among 214 HIV-positive female patients on antiretroviral therapy (ART) in Brazil. The prevalence of vitamin D deficiency (< 30 ng/ml) was 40.65% (87/214). Hypercholesterolemia, high LDL-c, duration of use of current antiretroviral regimen, hypertriglyceridemia, body mass index, age, hypertension, time with AIDS ≥ 10 years and hyperglycemia were selected for multivariate analysis (p < 0.20). After this analysis, hypercholesterolemia and use of current antiretroviral regimen ≥ 3 years remained independently associated with vitamin D deficiency. There was an inverse statistically significant correlation between total cholesterol and serum 25(OH)D levels. High prevalence of vitamin D deficiency was found among HIV-positive women on ART and was independently associated with its prolonged use and with hypercholesterolemia.

Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in breast milk.

PubMed

Shapiro, Roger L; Ndung'u, Thumbi; Lockman, Shahin; Smeaton, Laura M; Thior, Ibou; Wester, Carolyn; Stevens, Lisa; Sebetso, Gaseene; Gaseitsiwe, Simani; Peter, Trevor; Essex, Max

2005-09-01

The ability of highly active antiretroviral therapy (HAART) to reduce human immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not been described. We compared breast-milk HIV-1 RNA and DNA loads of women in Botswana who received HAART (nevirapine, lamivudine, and zidovudine) and women who did not receive HAART. Women in the HAART group received treatment for a median of 98 days (range, 67-222 days) at the time of breast-milk sampling; 23 (88%) of 26 had whole breast-milk HIV-1 RNA loads <50 copies/mL, compared with 9 (36%) of 25 women who did not receive HAART (P=.0001). This finding remained significant in a multivariate logistic-regression model (P = .0006). The whole-milk HIV-1 DNA load was unaffected by HAART. Of women who received HAART, 13 (50%) of 26 had HIV-1 DNA loads <10 copies/10(6) cells, compared with 15 (65%) of 23 who did not receive HAART (P = .39). HAART suppressed cell-free HIV-1 RNA in breast milk and may therefore reduce mother-to-child transmission (MTCT) of HIV-1 via breast-feeding. However, HAART initiated during pregnancy or early after delivery had no apparent effect on cell-associated HIV-1 DNA loads in breast milk. Clinical trials to determine MTCT among breast-feeding women receiving HAART are needed.

AIDS in Brazilian children: history, surveillance, antiretroviral therapy, and epidemiologic transition, 1984-2008.

PubMed

Ramos, Alberto Novaes; Matida, Luiza Harunari; Hearst, Norman; Heukelbach, Jorg

2011-04-01

We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges.

The Promise of Antiretrovirals for HIV Prevention

PubMed Central

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

2013-01-01

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

Effect of age on immunological response in the first year of antiretroviral therapy in HIV-1-infected adults in West Africa.

PubMed

Balestre, Eric; Eholié, Serge P; Lokossue, Amani; Sow, Papa Salif; Charurat, Man; Minga, Albert; Drabo, Joseph; Dabis, François; Ekouevi, Didier K; Thiébaut, Rodolphe

2012-05-15

To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context. The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4 gain over 12 months of ART was estimated using linear mixed models. Models were adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar period and ART regimen. The total number of patients included was 24,107, contributing for 50,893 measures of CD4 cell count in the first year of ART. The baseline median CD4 cell count was 144 cells/μl [interquartile range (IQR) 61-235]; median CD4 cell count reached 310 cells/μl (IQR 204-443) after 1 year of ART. The median age at treatment initiation was 36.3 years (10th-90th percentiles = 26.5-50.1). In adjusted analysis, the mean CD4 gain was significantly higher in younger patients (P < 0.0001). At 12 months, patients below 30 years recovered an additional 22 cells/μl on average [95% confidence interval (CI) 2-43] compared to patients at least 50 years. Among HIV-infected adults in West Africa, the immunological response after 12 months of ART was significantly poorer in elderly patients. As the population of treated patients is likely to get older, the impact of this age effect on immunological response to ART may increase over time.

Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008–2013

PubMed Central

Fox, Matthew P; MPA, Sydney Rosen

2015-01-01

Background We previously published systematic reviews of retention in care after antiretroviral therapy initiation among general adult populations in sub-Saharan Africa. We estimated 36-month retention at 73% for publications from 2007–2010. This report extends the review to cover 2008–2013 and expands it to all low- and middle-income countries. Methods We searched PubMed, Embase, Cochrane Register, and ISI Web of Science from January 1, 2008 to December 31, 2013 and abstracts from AIDS and IAS from 2008–2013. We estimated retention across cohorts using simple averages and interpolated missing times through the last time reported. We estimated all-cause attrition (death, loss to follow-up) for patients receiving first-line ART in routine settings in low- and middle-income countries. Results We found 123 papers and abstracts reporting retention for 154 patient cohorts and 1,554,773 patients in 42 countries. Overall, 43% of all patients not retained were known to have died. Unweighted averages of reported retention was 78%, 71% and 69% at 12, 24, and 36 months after treatment initiation, respectively. We estimated 36-month retention at 65% in Africa, 80% in Asia, and 64% in Latin America and the Caribbean. From lifetable analysis, we estimated retention at 12, 24, 36, 48 and 60 months at 83%, 74%, 68%, 64% and 60%, respectively. Conclusions Retention at 36 months on treatment averages 65–70%. There are several important gaps in the evidence-base, which could be filled by further research, especially in terms of geographic coverage and duration of follow-up. PMID:25942461

Excellent clinical outcomes and retention in care for adults with HIV-associated Kaposi sarcoma treated with systemic chemotherapy and integrated antiretroviral therapy in rural Malawi.

PubMed

Herce, Michael E; Kalanga, Noel; Wroe, Emily B; Keck, James W; Chingoli, Felix; Tengatenga, Listern; Gopal, Satish; Phiri, Atupere; Mailosi, Bright; Bazile, Junior; Beste, Jason A; Elmore, Shekinah N; Crocker, Jonathan T; Rigodon, Jonas

2015-01-01

HIV-associated Kaposi sarcoma (HIV-KS) is the most common cancer in Malawi. In 2008, the non-governmental organization, Partners In Health, and the Ministry of Health established the Neno Kaposi Sarcoma Clinic (NKSC) to treat HIV-KS in rural Neno district. We aimed to evaluate 12-month clinical outcomes and retention in care for HIV-KS patients in the NKSC, and to describe our implementation model, which featured protocol-guided chemotherapy, integrated antiretroviral therapy (ART) and psychosocial support delivered by community health workers. We conducted a retrospective cohort study using routine clinical data from 114 adult HIV-KS patients who received ART and ≥1 chemotherapy cycle in the NKSC between March 2008 and February 2012. At enrolment 97% of patients (n/N=103/106) had advanced HIV-KS (stage T1). Most patients were male (n/N=85/114, 75%) with median age 36 years (interquartile range, IQR: 29-42). Patients started ART a median of 77 days prior to chemotherapy (IQR: 36-252), with 97% (n/N=105/108) receiving nevirapine/lamivudine/stavudine. Following standardized protocols, we treated 20 patients (18%) with first-line paclitaxel and 94 patients (82%) with bleomycin plus vincristine (BV). Of the 94 BV patients, 24 (26%) failed to respond to BV requiring change to second-line paclitaxel. A Division of AIDS grade 3/4 adverse event occurred in 29% of patients (n/N=30/102). Neutropenia was the most common grade 3/4 event (n/N=17/102, 17%). Twelve months after chemotherapy initiation, 83% of patients (95% CI: 74-89%) were alive, including 88 (77%) retained in care. Overall survival (OS) at 12 months did not differ by initial chemotherapy regimen (p=0.6). Among patients with T1 disease, low body mass index (BMI) (adjusted hazard ratio, aHR=4.10, 95% CI: 1.06-15.89) and 1 g/dL decrease in baseline haemoglobin (aHR=1.52, 95% CI: 1.03-2.25) were associated with increased death or loss to follow-up at 12 months. The NKSC model resulted in infrequent adverse events

Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

PubMed Central

Rathbun, R. Chris; Liedtke, Michelle D.

2011-01-01

Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed. PMID:24309307

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

Combination antiretroviral use and preterm birth.

PubMed

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

2013-02-15

Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. 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. 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. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.

Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.

PubMed

Tenforde, Mark W; Yadav, Ashish; Dowdy, David W; Gupte, Nikhil; Shivakoti, Rupak; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Christian, Parul; Semba, Richard D; Campbell, Thomas B; Gupta, Amita

2017-07-01

Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized. We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models. Median pretreatment CD4 T-cell count was 170 cells/mm; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART. In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.

Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality.

PubMed

Glass, Tracy R; Sterne, Jonathan A C; Schneider, Marie-Paule; De Geest, Sabina; Nicca, Dunja; Furrer, Hansjakob; Günthard, Huldrych F; Bernasconi, Enos; Calmy, Alexandra; Rickenbach, Martin; Battegay, Manuel; Bucher, Heiner C

2015-10-23

To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. Prospective observational cohort study. Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Imported Acquired Immunodeficiency Syndrome–Related Histoplasmosis in Metropolitan France: A Comparison of Pre–Highly Active Anti-Retroviral Therapy and Highly Active Anti-Retroviral Therapy Eras

PubMed Central

Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

2011-01-01

Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome–related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985–1994) and HAART (1997–2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome–related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era. PMID:22049053

Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults.

PubMed

Mave, Vidya; Erlandson, Kristine M; Gupte, Nikhil; Balagopal, Ashwin; Asmuth, David M; Campbell, Thomas B; Smeaton, Laura; Kumarasamy, Nagalingeswaran; Hakim, James; Santos, Breno; Riviere, Cynthia; Hosseinipour, Mina C; Sugandhavesa, Patcharaphan; Infante, Rosa; Pillay, Sandy; Cardoso, Sandra W; Tripathy, Srikanth; Mwelase, Noluthando; Berendes, Sima; Andrade, Bruno B; Thomas, David L; Bollinger, Robert C; Gupta, Amita

2016-07-01

Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown. Among a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models. Of 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P = .01), and the decreases in both CRP (P = .01) and interleukin 18 (P = .02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10 increase in soluble CD14 level (P = .05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P = .001). Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Biomarkers From Late Pregnancy to 6 Weeks Postpartum in HIV-Infected Women Who Continue Versus Discontinue Antiretroviral Therapy After Delivery

PubMed Central

Hoffman, Risa M.; Leister, Erin; Kacanek, Deborah; Shapiro, David E.; Read, Jennifer S.; Bryson, Yvonne; Currier, Judith S.

2013-01-01

Background Women who use antiretroviral therapy (ART) solely for the prevention of mother-to-child transmission of HIV discontinue postpartum. We hypothesized that women discontinuing ART by 6 weeks postpartum (“discontinuers”) would have elevated postpartum inflammatory biomarker levels relative to women remaining on ART postpartum (“continuers”). Methods Data from HIV-infected pregnant women enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 with CD4 counts >350 cells per cubic millimeter before initiating ART or first pregnancy CD4 counts >400 cells per cubic millimeter after starting ART and with available stored plasma samples at >20 weeks of gestation, delivery, and 6 weeks postpartum were analyzed. Plasma samples were tested for highly sensitive C-reactive protein, D-dimer, and interleukin-6. We used longitudinal linear spline regression to model biomarkers over time. Results Data from 128 women (65 continuers and 63 discontinuers) were analyzed. All biomarkers increased from late pregnancy to delivery, then decreased postpartum (slopes different from 0, P < 0.001). Continuers had a steeper decrease in log D-dimer between delivery and 6 weeks postpartum than discontinuers (P = 0.002). Conclusions In contrast to results from treatment interruption studies in adults, both ART continuers and ART discontinuers had significant decreases in the levels of D-dimer, highly sensitive C-reactive protein, or interleukin-6 postpartum. Continuation was associated with a more rapid decline in D-dimer levels compared with discontinuation. PMID:23714738

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

Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study

PubMed Central

Gompels, Mark; Delpech, Valerie; Porter, Kholoud; Post, Frank; Johnson, Margaret; Dunn, David; Palfreeman, Adrian; Gilson, Richard; Gazzard, Brian; Hill, Teresa; Walsh, John; Fisher, Martin; Orkin, Chloe; Ainsworth, Jonathan; Bansi, Loveleen; Phillips, Andrew; Leen, Clifford; Nelson, Mark; Anderson, Jane; Sabin, Caroline

2011-01-01

Objectives To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm3 at start of antiretroviral therapy. Design Cohort study. Setting Outpatient HIV clinics throughout the United Kingdom. Population Adult patients from the UK Collaborative HIV Cohort (UK CHIC) Study with CD4 count ≤350 cells/mm3 at start of antiretroviral therapy in 1996-2008. Main outcome measures Life expectancy at the exact age of 20 (the average additional years that will be lived by a person after age 20), according to the cross sectional age specific mortality rates during the study period. Results 1248 of 17 661 eligible patients died during 91 203 person years’ follow-up. Life expectancy (standard error) at exact age 20 increased from 30.0 (1.2) to 45.8 (1.7) years from 1996-9 to 2006-8. Life expectancy was 39.5 (0.45) for male patients and 50.2 (0.45) years for female patients compared with 57.8 and 61.6 years for men and women in the general population (1996-2006). Starting antiretroviral therapy later than guidelines suggest resulted in up to 15 years’ loss of life: at age 20, life expectancy was 37.9 (1.3), 41.0 (2.2), and 53.4 (1.2) years in those starting antiretroviral therapy with CD4 count <100, 100-199, and 200-350 cells/mm3, respectively. Conclusions Life expectancy in people treated for HIV infection has increased by over 15 years during 1996-2008, but is still about 13 years less than that of the UK population. The higher life expectancy in women is magnified in those with HIV. Earlier diagnosis and subsequent timely treatment with antiretroviral therapy might increase life expectancy. PMID:21990260

Self-reported Dietary Intake and Appetite Predict Early Treatment Outcome among Low Body Mass Index Adults Initiating HIV Treatment in sub-Saharan Africa

PubMed Central

Koethe, John R.; Blevins, Meridith; Bosire, Claire; Nyirenda, Christopher; Kabagambe, Edmond K.; Mwango, Albert; Kasongo, Webster; Zulu, Isaac; Shepherd, Bryan E.; Heimburger, Douglas C.

2013-01-01

Objective Low body mass index (BMI) is a major risk factor for early mortality among HIV infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa, and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake, and treatment outcome 12 weeks after ART initiation among HIV infected adults with advanced malnutrition and immunosuppression. Design A prospective, observational cohort study. Dietary intake was assessed using a 24-hour recall survey. The relationships of appetite, intake, and treatment outcome were analyzed using time-varying Cox models. Setting A public-sector HIV clinic in Lusaka, Zambia. Subjects 142 HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/µl. Results Median age, BMI, and CD4+ lymphocyte count were 32 years, 16 kg/m2, and 34 cells/µL, respectively. Twenty-five participants (18%) died before 12 weeks, and another 33 (23%) were lost to care. A 500 kJ/day higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (AHR 0.84; p=0.01), but the relative contribution of carbohydrate, protein, and fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors, and hunger was rarely reported. Conclusions Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition, and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted. PMID:22691872

[Antiretroviral therapy for HIV-infected patients with schizophrenia. Coordinated multidisciplinary management (7 cases)].

PubMed

Leclerc, Stéphanie; Brunschwig, Olivier; Berki-Benhaddad, Zhora; Soyris, Dominique; Grataud, Christian; Breton, Guillaume; Leport, Catherine; Vildé, Jean-Louis

2005-03-26

Schizophrenia might appear to be an obstacle to the initiation of and especially compliance with antiretroviral therapy for HIV-infected patients. The aims of this study were to describe the clinical, immunologic and virologic course after initiation of antiretroviral therapy in 7 HIV patients with schizophrenia (according to DSM-IV-R criteria), and to analyse the possibilities of an adequate antiretroviral therapy for those patients. Multidisciplinary management by specialists in infectious diseases, addiction-related disorders, treatment adherence and compliance, and psychiatrists, as well as social workers, home care agencies, and patient advocacy and assistance groups, was organized with coordinated medical-psychiatric follow-up at least once a month. The patients, 6 men and 1 woman, were aged from 26 to 48 years; schizophrenia had been diagnosed in 5 patients 6 months to 20 years before the HIV infection was discovered; diagnoses of both diseases were essentially simultaneous for the other 2. All patients took long-term neuroleptics for their schizophrenia. Two were active drug addicts who received drug substitution treatment. Before antiretroviral treatment began, 6 patients had advanced infection: stage C with peak CD4 cell counts ranging from 6 to 70/mm3; they began treatment with protease inhibitors between May 1996 and August 1997. The seventh patient was first seen during primary HIV infection in July 1998, and treatment began then. Response to antiretroviral treatment with protease inhibitors was slow for all patients, but viral load became undetectable for 6 of the 7, after 5 months to 4 years; 3 had opportunistic infections. Follow-up ended in January 2002: 5 patients still had undetectable viral loads,, with CD4 cell counts ranging from 45 to 1 000/mm3. One patient died from mixed terminal cirrhosis (alcohol abuse and hepatitis C); the viral load in another was only partially controlled (10 000 copies/ml), because of poor treatment adherence

Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana A Randomized Clinical Trial

PubMed Central

Baum, Marianna K.; Campa, Adriana; Lai, Shenghan; Martinez, Sabrina Sales; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W.; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2015-01-01

IMPORTANCE Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of

Outcomes of antiretroviral therapy in children in Asia and Africa: a comparative analysis of the IeDEA pediatric multiregional collaboration

PubMed Central

Leroy, Valeriane; Malateste, Karen; Rabie, Helena; Lumbiganon, Pagakrong; Ayaya, Samuel; Dicko, Fatoumata; Davies, Mary-Ann; Kariminia, Azar; Wools-Kaloustian, Kara; Aka, Edmond; Phiri, Samuel; Aurpibul, Linda; Yiannoutsos, Constantin; Signaté-Sy, Haby; Mofenson, Lynne; Dabis, François

2013-01-01

Background We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods HIV-infected children (positive PCR <18 months or positive serology ≥18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). Findings Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. Conclusion Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level. PMID:23187940

HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

PubMed

Kotler, Donald P

2008-09-01

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

PubMed

Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

2017-06-01

To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

Antiretroviral drug use and HIV drug resistance among MSM and transgender women in sub-Saharan Africa.

PubMed

Zhang, Yinfeng; Fogel, Jessica M; Guo, Xu; Clarke, William; Breaud, Autumn; Cummings, Vanessa; Hamilton, Erica L; Ogendo, Arthur; Kayange, Noel; Panchia, Ravindre; Dominguez, Karen; Chen, Ying Q; Sandfort, Theodorus; Eshleman, Susan H

2018-06-19

To analyze antiretroviral drug use and HIV drug resistance among HIV-infected MSM and transgender women who were screened for participation in the HIV Prevention Trials Network 075 study. A qualitative assay was used to detect 20 antiretroviral drugs in five drug classes; this assay is based on liquid chromatography coupled with high-resolution accurate-mass mass spectrometry. HIV viral load testing was performed using the RealTime HIV-1 Viral Load Assay. HIV drug resistance testing was performed using the ViroSeq HIV-1 Genotyping System. Logistic regression was used to evaluate factors associated with study outcomes. Antiretroviral drugs were detected in 63 (34.4%) of 183 participants who had confirmed HIV infection at screening; 11 (17.5%) of the 63 participants were not virally suppressed. Six (54.5%) of the 11 participants had drug-resistant HIV, including four who had multiclass resistance. Seven (63.6%) of the 11 were at risk of acquiring resistance to additional antiretroviral drugs. In multivariate model, antiretroviral drugs were more frequently detected in older participants, those recruited from Kisumu, Kenya, and those who reported ever having been in HIV care or on antiretroviral therapy (ART). Most of HIV-infected persons screened for participation in HIV Prevention Trials Network 075 were not on ART, and many of those who were on ART were not virally suppressed. Many of those participants had drug-resistant HIV. These findings highlight the need for improved HIV care for African MSM and transgender women.

Access to antiretroviral drugs and AIDS management in Senegal.

PubMed

Desclaux, Alice; Ciss, Mounirou; Taverne, Bernard; Sow, Papa S; Egrot, Marc; Faye, Mame A; Lanièce, Isabelle; Sylla, Omar; Delaporte, Eric; Ndoye, Ibrahima

2003-07-01

Description and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. ISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations. Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. The ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.

Attrition from antiretroviral treatment services among pregnant and non-pregnant patients following adoption of Option B+ in Haiti.

PubMed

Domercant, Jean Wysler; Puttkammer, Nancy; Young, Paul; Yuhas, Krista; François, Kesner; Grand'Pierre, Reynold; Lowrance, David; Adler, Michelle

2017-01-01

Access to antiretroviral therapy (ART) has expanded in Haiti because of the adoption of Option B+ and the revision of treatment guidelines. Retention in care and treatment varies greatly and few studies have examined retention rates, particularly among women enrolled in Option B+. To assess attrition among pregnant and non-pregnant patients initiating ART following adoption of Option B+ in Haiti. Longitudinal data of adult patients initiated on ART from October 2012 through August 2014 at 73 health facilities across Haiti were analyzed using a survival analysis framework to determine levels of attrition. The Kaplan-Meier method and Cox proportional hazards regression were used to examine risk factors associated with attrition. Among 17,059 patients who initiated ART, 7627 (44.7%) were non-pregnant women, 5899 (34.6%) were men, and 3533 (20.7%) were Option B+ clients. Attrition from the ART program was 36.7% at 12 months (95% CI: 35.9-37.5%). Option B+ patients had the highest level of attrition at 50.4% at 12 months (95% CI: 48.6-52.3%). While early HIV disease stage at ART initiation was protective among non-pregnant women and men, it was a strong risk factor among Option B+ clients. In adjusted analyses, key protective factors were older age (p < 0.0001), living near the health facility (p = 0.04), having another known HIV-positive household member (p < 0.0001), having greater body mass index (BMI) (p < 0.0001), pre-ART counseling (p < 0.0001), and Cotrimoxazole prophylaxis during baseline (p < 0.01). Higher attrition was associated with rapidly starting ART after enrollment (p < 0.0001), anemia (p < 0.0001), and regimen tenofovir+lamivudine+nevirapine (TDF+3TC+NVP) (p < 0.001). ART attrition in Haiti is high among adults, especially among Option B+ patients. Identifying newly initiated patients most at risk for attrition and providing appropriate interventions could help reduce ART attrition.

Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study.

PubMed

Gunda, Daniel W; Kilonzo, Semvua B; Kamugisha, Erasmus; Rauya, Engelbert Z; Mpondo, Bonaventura C

2017-06-08

Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body's capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania. A retrospective analysis of adult HIV patients' data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies. A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage. Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome.

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

Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.

PubMed

Maru, Duncan Smith-Rohrberg; Kozal, Michael J; Bruce, R Douglas; Springer, Sandra A; Altice, Frederick L

2007-12-15

Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.

Diet quality of persons living with HIV/AIDS on highly active antiretroviral therapy.

PubMed

Duran, A C F L; Almeida, L B; Segurado, A A C; Jaime, P C

2008-08-01

This study sought to assess the diet quality of individuals living with HIV/AIDS who were receiving antiretroviral therapy in São Paulo, Brazil. This cross-sectional study involved 56 HIV-infected adults. Demographic and anthropometric data were collected, and diet quality was measured using the Healthy Eating Index (HEI), modified for Brazilians, which included ten components: adequacy of intake of six different food groups, total fat, cholesterol, dietary fibre and dietary variety. Among the individuals assessed, 64.3% of the participants had a diet needing improvement, while 8.7% had a poor diet. The overall HEI score was 68.3 points (SD = 14.9). Mean scores were low for fruits, vegetables, dairy products and dietary fibre; and high for meats and eggs, total fat and cholesterol. The overall HEI score was higher among individuals who were not overweight (P = 0.003), who were also more likely to achieve dietary goals for dairy products (P = 0.039) and grains (P = 0.005). Most of these adults living with HIV/AIDS had diets that required improvement, and being overweight was associated with poorer diet quality. Nutritional interventions aimed at maintaining healthy body weight and diet should be taken into account in caring for HIV-infected people.

The Physical and Mental Health of Head Start Staff: The Pennsylvania Head Start Staff Wellness Survey, 2012

PubMed Central

Becker, Brandon D.; Herman, Allison N.; Gooze, Rachel A.

2013-01-01

Introduction Despite attention to the health of low-income children in Head Start, little is known about the health of adults working for the program. The objective of our study was to compare the physical and mental health of women working in Pennsylvania Head Start programs with the health of US women who have similar sociodemographic characteristics. Methods We used data from a web-based survey in 2012 in which 2,199 of 3,375 (65.2%) staff in 66 Pennsylvania Head Start programs participated. For the 2,122 female respondents, we determined the prevalence of fair or poor health status, frequent (≥14 d/mo) unhealthy days, frequent (≥10 d/y) work absences due to illness, diagnosed depression, and 3 or more of 6 physical health conditions. We compared these prevalences with those found in 2 national samples of employed women of similar age, education, race/ethnicity, and marital status. Results Among Head Start staff, 85.7% were non-Hispanic white, 62.4% were married, and 60.3% had completed college. The prevalence (% [95% confidence interval]) of several health indicators was higher in Head Start staff than in the national samples: fair or poor health (14.6% [13.1%–16.1%] vs 5.1% [4.5%–5.6%]), frequent unhealthy days (28.3% [26.3%–30.2%] vs 14.5% [14.1%–14.9%]), diagnosed depression (23.5% [21.7%–25.3%] vs 17.6% [17.1%–18.0%]), and 3 or more physical health conditions (21.8% [20.0%–23.6%] vs 12.6% [11.7%–13.5%]). Conclusion Women working with children in Head Start programs have poorer physical and mental health than do US women who have similar sociodemographic characteristics. PMID:24176085

The impact of herbal remedies on adverse effects and quality of life in HIV-infected individuals on antiretroviral therapy

PubMed Central

Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D

2012-01-01

Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS.

PubMed

Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

2013-09-17

There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥ 18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7 g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was-2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p ≤ 0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ≥ 1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p ≤ 0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤-3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). Severe

Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand

PubMed Central

Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

2013-01-01

The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012–May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made. PMID:23986652

Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand.

PubMed

Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

2013-01-01

The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012-May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made.

Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa.

PubMed

Sempa, Joseph B; Ujeneza, Eva L; Nieuwoudt, Martin

2017-01-01

In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. 'Preferred Reporting Items for Systematic Review and Meta-Analyses' guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: 'slope', 'survival', and 'asymptote' models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to define 'prior' knowledge in the Bayesian sense. Such

It's Not Just the Pills: A Qualitative Meta-Synthesis of HIV Antiretroviral Adherence Research.

PubMed

Barroso, Julie; Leblanc, Natalie M; Flores, Dalmacio

Antiretroviral therapy (ART) improves the health and longevity of people living with HIV infection (PLWH) and also prevents transmission of the virus. Yet, lack of adherence to ART regimens has been a persistent problem, even with simpler regimens. Guidelines that deal with ART adherence are based almost solely on quantitative studies; this focus ignores the context and complexity of patients' lives. Guidelines are also focused on the individual. We argue that the solution is to include the broader communities in which patients live, and to deal with systemic disparities that persist worldwide; this can be done in part through demedicalizing HIV care for healthy PLWH. We present findings from a qualitative meta-synthesis of 127 studies conducted around the world on the last two pillars of the HIV treatment cascade: starting and remaining on ART until optimal viral suppression is achieved. We use Maslow's hierarchy of needs to frame our findings. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

CD4 responses in the setting or suboptimal virological responses to antiretroviral therapy: features, outcomes, and associated factors.

PubMed

Collazos, Julio; Asensi, Víctor; Cartón, José Antonio

2009-07-01

The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

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

PubMed

McGowan, Ian

2014-06-01

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

Photosensitization is required for antiretroviral activity of hypericin

NASA Astrophysics Data System (ADS)

Carpenter, Susan; Tossberg, John; Kraus, George A.

1991-06-01

In a seminal series of papers, Meruelo and co-workers have described the potent antiretroviral effect of hypericin. Interestingly, hypericin was found to inhibit not only the production of infectious virus from chronically infected cells, but was also shown to directly inhibit reverse transcriptase activity of mature virions. The effect of hypericin on cells chronically infected with equine infectious anemia virus (EIAV), a retrovirus genetically related to HIV, is demonstrated. At concentrations of 10 (mu) g/ml, hypericin reduced production of infectious EIAV by 99.99 without causing obvious cytopathic effects. Interestingly, the results indicated that the antiretroviral activity of hypericin was wholly dependent on the presence of light. No decrease in viral infectivity was observed when hypericin and virus were incubated in the dark. Moreover, it appeared that light was an absolute requirement for the antiviral activity, as even high concentrations of hypericin (10 (mu) g/ml) were unable to reduce infectivity of as few as 100 infectious virions.

Early mortality among children and adults in antiretroviral therapy programs in Southwest Ethiopia, 2003-15.

PubMed

Gesesew, Hailay Abrha; Ward, Paul; Woldemichael, Kifle; Mwanri, Lillian

2018-01-01

Several studies reported that the majority of deaths in HIV-infected people are documented in their early antiretroviral therapy (ART) follow-ups. Early mortality refers to death of people on ART for follow up period of below 24 months due to any cause. The current study assessed predictors of early HIV mortality in Southwest Ethiopia. We have conducted a retrospective analysis of 5299 patient records dating from June 2003- March 2015. To estimate survival time and compare the time to event among the different groups of patients, we used a Kaplan Meir curve and log-rank test. To identify mortality predictors, we used a cox regression analysis. We used SPSS-20 for all analyses. A total of 326 patients died in the 12 years follow-up period contributing to 6.2% cumulative incidence and 21.7 deaths per 1000 person-year observations incidence rate. Eighty-nine percent of the total deaths were documented in the first two years follow up-an early-term ART follow up. Early HIV mortality rates among adults were 50% less in separated, divorced or widowed patients compared with never married patients, 1.6 times higher in patients with baseline CD4 count <200 cells/μL compared to baseline CD4 count ≥200 cells/μL, 1.5 times higher in patients with baseline WHO clinical stage 3 or 4 compared to baseline WHO clinical stage 1 or 2, 2.1 times higher in patients with immunologic failure compared with no immunologic failure, 60% less in patients with fair or poor compared with good adherence, 2.9 times higher in patients with bedridden functional status compared to working functional status, and 2.7 times higher with patients who had no history of HIV testing before diagnosis compared to those who had history of HIV testing. Most predictors of early mortality remained the same to the predictors of an overall HIV mortality. When discontinuation was assumed as an event, the predictors of an overall HIV mortality included age between 25-50 years, base line CD4 count, developing

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

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

PubMed

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

2013-11-21

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. 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. 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). 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 hospitals.

The Start of Head Start

ERIC Educational Resources Information Center

Neugebauer, Roger

2010-01-01

The creation of the Head Start program occurred at break-neck speed with many dramatic turns and many colorful players. No one tells the story better than Edward Zigler in "Head Start: The Inside Story of America's Most Successful Educational Experiment"--a detailed and personal, behind the scenes look at the program's inception. From this…

Implementing antiretroviral therapy programs in resource-constrained settings: lessons from Monze, Zambia.

PubMed

Adedimeji, Adebola; Malokota, Oliver; Manafa, Ogenna

2011-05-01

We describe the impact of an antiretroviral therapy program on human resource utilization and service delivery in a rural hospital in Monze, Zambia, using qualitative data. We assess project impact on staff capacity utilization, service delivery, and community perception of care. Increased workload resulted in fatigue, low staff morale, and exacerbated critical manpower shortages, but also an increase in users of antiretroviral therapy, improvement in hospital infrastructure and funding, and an overall community satisfaction with service delivery. Integrating HAART programs within existing hospital units and services may be a good alternative to increase overall efficiency.

Fears about antiretroviral therapy among users of the internet forum for people living with HIV/AIDS in Russia.

PubMed

Dudina, Victoria I; Judina, Darja I; King, Elizabeth J

2017-02-01

The purpose of this research was to identify different types of fear related to starting and adhering to antiretroviral therapy (ART) among people living with HIV (PLHIV) in Russia. Data were collected from the Russian-language internet forum for PLHIV (hivlife.info). Qualitative data analysis focused on the sections of the forum where users discussed health-related issues in order to identify fears related to HIV treatment. The following types of fear were revealed: fear of the illness, fear to learn negative information about one's health, fear of side effects, fear of therapy to be ineffective, fear that the appropriate medications will become unavailable, fear of lifestyle changes, and fear for the well-being of significant others. Efforts to increase the uptake of and adherence to ART should take into account the fears of PLHIV.

Impact of drug stock-outs on death and retention to care among HIV-infected patients on combination antiretroviral therapy in Abidjan, Côte d'Ivoire.

PubMed

Pasquet, Armelle; Messou, Eugène; Gabillard, Delphine; Minga, Albert; Depoulosky, Ayeby; Deuffic-Burban, Sylvie; Losina, Elena; Freedberg, Kenneth A; Danel, Christine; Anglaret, Xavier; Yazdanpanah, Yazdan

2010-10-15

To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire. We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16). cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs.

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

PubMed Central

Amon, Joseph J

2008-01-01

Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts. PMID:18304316

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

PubMed

Tsuchiya, Naho; Pathipvanich, Panita; Wichukchinda, Nuanjun; Rojanawiwat, Archawin; Auwanit, Wattana; Ariyoshi, Koya; Sawanpanyalert, Pathom

2014-10-30

Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand. All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models. Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification. HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and

Cost-efficacy analysis of the MONET trial using UK antiretroviral drug prices.

PubMed

Gazzard, Brian; Hill, Andrew; Anceau, Anne

2011-07-01

In virologically suppressed patients, switching to darunavir/ritonavir (DRV/r) monotherapy maintains HIV RNA suppression, and could also lower treatment costs. The purpose of this analysis was to calculate the potential cost savings from the use of DRV/r monotherapy in the UK. In the MONET trial, 256 patients with HIV RNA < 50 copies/mL on current highly active antiretroviral therapy (HAART) for over 24 weeks (non-nucleoside reverse-transcriptase inhibitor [NNRTI] based [43%] or protease inhibitor [PI] based [57%]), switched to DRV/r 800/100 mg once daily, either as monotherapy (n = 127) or with two NRTIs (n = 129). The UK costs per patient with HIV RNA < 50 copies/mL at week 48 (responders) were calculated using a 'switch included' analysis to account for additional antiretrovirals taken after initial treatment failure. By this analysis, efficacy was 93.5% versus 95.1% in the DRV/r monotherapy and triple therapy arms, respectively. British National Formulary 2009 values were used. Before the trial, the mean annual cost of antiretrovirals was £6906 for patients receiving NNRTI-based HAART, and £8348 for patients receiving PI-based HAART. During the MONET trial, the mean annual per-patient cost of antiretrovirals was £8642 in the triple therapy arm, of which 55% was from NRTIs and 45% from PIs. The mean per-patient cost in the monotherapy arm was £4126, a saving of 52% versus triple therapy. The mean cost per responder was £9085 in the triple therapy arm versus £4413 in the DRV/r monotherapy arm. Based on the MONET results, the lower cost of DRV/r monotherapy versus triple therapy in the UK would allow more patients to be treated for fixed budgets, while maintaining HIV RNA suppression at < 50 copies/mL. If all patients meeting the inclusion criteria of the MONET trial in the UK were switched to DRV/r monotherapy, there is the potential to save up to £60 million in antiretroviral drug costs from the UK NHS budget.

Five-year trends in antiretroviral usage and drug costs in HIV-infected children in Thailand.

PubMed

Collins, Intira; Cairns, John; Le Coeur, Sophie; Pagdi, Karin; Ngampiyaskul, Chaiwat; Layangool, Prapaisri; Borkird, Thitiporn; Na-Rajsima, Sathaporn; Wanchaitanawong, Vanichaya; Jourdain, Gonzague; Lallemant, Marc

2013-09-01

As antiretroviral treatment (ART) programs mature, data on drug utilization and costs are needed to assess durability of treatments and inform program planning. Children initiating ART were followed up in an observational cohort in Thailand. Treatment histories from 1999 to 2009 were reviewed. Treatment changes were categorized as: drug substitution (within class), switch across drug class (non nucleoside reverse-transcriptase inhibitors (NNRTI) to/from protease inhibitor (PI)), and to salvage therapy (dual PI or PI and NNRTI). Antiretroviral drug costs were calculated in 6-month cycles (US$ 2009 prices). Predictors of high drug cost including characteristics at start of ART (baseline), initial regimen, treatment change, and duration on ART were assessed using mixed-effects regression models. Five hundred seven children initiated ART with a median 54 (interquartile range, 36-72) months of follow-up. Fifty-two percent had a drug substitution, 21% switched across class, and 2% to salvage therapy. When allowing for drug substitution, 78% remained on their initial regimen. Mean drug cost increased from $251 to $428 per child per year in the first and fifth year of therapy, respectively. PI-based and salvage regimens accounted for 16% and 2% of treatments prescribed and 33% and 5% of total costs, respectively. Predictors of high cost include baseline age ≥ 8 years, non nevirapine-based initial regimen, switch across drug class, and to salvage regimen (P < 0.005). At 5 years, 21% of children switched across drug class and 2% received salvage therapy. The mean drug cost increased by 70%. Access to affordable second- and third-line drugs is essential for the sustainability of treatment programs.

Benefits of adherence to psychotropic medications on depressive symptoms and antiretroviral medication adherence among men and women living with HIV/AIDS.

PubMed

Cruess, Dean G; Kalichman, Seth C; Amaral, Christine; Swetzes, Connie; Cherry, Chauncey; Kalichman, Moira O

2012-04-01

Psychotropic medications are commonly used for depressive symptoms among people living with HIV/AIDS. We examined the relationships between adherence to psychotropic medications, depressive symptoms, and antiretroviral adherence. We assessed depressive symptoms among 324 people living with HIV/AIDS across a 3-month period (70% men; mean age 45 years; 90% African-American). Psychotropic and antiretroviral adherence was assessed using monthly, unannounced telephone pill counts. Multiple-regression and mediation analyses were utilized to examine associations under investigation. Greater depressive symptoms were associated with lower antiretroviral and psychotropic medication adherence. Greater adherence to psychotropic medications regardless of medication class was positively related to higher antiretroviral adherence. Greater adherence to psychotropic medications also significantly mediated the association between depressive symptoms and antiretroviral adherence. This study demonstrates the benefits of adherence to psychotropic medications on both depressive symptoms and antiretroviral adherence. Future work examining psychotropic medication adherence on disease outcomes in people living with HIV/AIDS is warranted.

Prevalence of antiretroviral drug resistance and resistance-associated mutations in antiretroviral therapy-naïve HIV-infected individuals from 40 United States cities.

PubMed

Ross, Lisa; Lim, Michael L; Liao, Qiming; Wine, Brian; Rodriguez, Allan E; Weinberg, Winkler; Shaefer, Mark

2007-01-01

Transmission of drug-resistant HIV strains to antiretroviral therapy (ART)-naïve subjects can negatively impact therapy response. As treatment strategies and utilization of antiretroviral drugs evolve, patterns of transmitted mutations may shift. Paired genotypic and phenotypic susceptibility data were retrospectively analyzed for 317 ART-naïve, HIV-infected subjects from 40 small and major metropolitan cities in the Northeastern, Midwestern, Southern, Southwestern, and Northwestern United States during 2003. Using current (January 2007) PhenoSense cutoffs, HIV-from 8% of subjects had reduced susceptibility to > or = 1 drug. By class, < 1% had reduced susceptibility to protease inhibitors (PIs), and 1% had reduced susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs); reduced susceptibility to > or = 1 non-nucleoside reverse transcriptase inhibitor (NNRTIs) was seen in 7% of subjects, with 4% of all subjects having reduced susceptibility to all NNRTIs. IAS-USA-defined NRTI, NNRTI, and/or major PI HIV-drug resistance-associated mutations were detected for 0% of the subjects. HIV risk factors included homosexual contact (74%), heterosexual contact (28%), and injectable drug use/transfusion/other (7%). Reduced susceptibility to > or = 1 drug was significantly higher (p = .034) for white subjects than African Americans and Hispanics/others. The high prevalence of drug resistance in these ART-naïve subjects suggests that transmitted resistance is occurring widely within the United States. HIV genotyping and/or phenotyping for antiretroviral-naïve patients seeking treatment should be considered, especially if the therapy will include an NNRTI.

Anti-retroviral therapy-induced status epilepticus in "pseudo-HIV serodeconversion".

PubMed

Etgen, Thorleif; Eberl, Bernhard; Freudenberger, Thomas

2010-01-01

Diligence in the interpretation of results is essential as information gained from the psychiatric patient's history might often be restricted. Nonobservance of established guidelines may lead to a wrong diagnosis, induce a false therapy and result in life-threatening situations. Communication errors between hospitals and doctors and uncritical acceptance of prior diagnoses add substantially to this problem. We present a patient with alcohol-related dementia who received anti-retroviral therapy that promoted a non-convulsive status epilepticus. HIV serodeconversion was considered after our laboratory result yielded a HIV-negative status. Critical review of previous diagnostic investigations revealed several errors in the diagnosis of HIV infection leading to a "pseudo-serodeconversion." Finally, anti-retroviral therapy could be discontinued. Copyright © 2010 Elsevier Inc. All rights reserved.

Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy.

PubMed

Arnedo, Mireia; Taffé, Patrick; Sahli, Roland; Furrer, Hansjakob; Hirschel, Bernard; Elzi, Luigia; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Bergmann, Sven; Beckmann, Jacques S; Telenti, Amalio; Tarr, Philip E

2007-09-01

HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy. The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids. Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score. Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.

Comparison of atazanavir/ritonavir and darunavir/ritonavir based antiretroviral therapy for antiretroviral naïve patients.

PubMed

Antoniou, Tony; Szadkowski, Leah; Walmsley, Sharon; Cooper, Curtis; Burchell, Ann N; Bayoumi, Ahmed M; Montaner, Julio S G; Loutfy, Mona; Klein, Marina B; Machouf, Nima; Tsoukas, Christos; Wong, Alexander; Hogg, Robert S; Raboud, Janet

2017-04-11

Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking. We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason). Additional endpoints included virologic failure, discontinuation due to virologic failure, discontinuation for other reasons, and virologic suppression. We studied 222 patients treated with darunavir/ritonavir and 1791 patients treated with atazanavir/ritonavir. Following multivariable adjustment, there was no difference between darunavir/ritonavir and atazanavir-ritonavir in the risk of regimen failure (adjusted hazard ratio 0.76, 95% CI 0.56 to 1.03) Darunavir/ritonavir-treated patients were at lower risk of virologic failure relative to atazanavir/ritonavir treated patients (aHR 0.50, 95% CI 0.28 to 0.91), findings driven largely by high rates of virologic failure among atazanavir/ritonavir-treated patients in the province of British Columbia. Of 108 discontinuations due to virologic failure, all occurred in patients starting atazanavir/ritonavir. There was no difference between regimens in time to discontinuation for reasons other than virologic failure (aHR 0.93; 95% CI 0.65 to 1.33) or virologic suppression (aHR 0.99, 95% CI 0.82 to 1.21). The risk of regimen failure was similar between patients treated with darunavir/ritonavir and atazanavir/ritonavir. Although darunavir/ritonavir was associated with a lower risk of virologic failure relative to atazanavir/ritonavir, this difference varied substantially by Canadian province and likely reflects regional variation in prescribing practices and patient

Subjective memory complaints are associated with poorer cognitive performance in adults with HIV.

PubMed

Kamkwalala, Asante; Hulgan, Todd; Newhouse, Paul

2017-05-01

With successful antiretroviral therapy in the US, HIV-positive adults now routinely survive into old age. However, increased life expectancy with HIV introduces the added complication of age-related cognitive decline. Aging with HIV has been associated with poorer cognitive outcomes compared to HIV-negative adults. While up to 50% of older HIV-positive adults will develop some degree of cognitive impairment over their lifetime, cognitive symptoms are often not consistently monitored, until those symptoms are significant enough to impair daily life. In this study we found that subjective memory complaint (SMC) ratings correlated with measurable memory performance impairments in HIV-positive adults, but not HIV-negative adults. As the HIV-positive population ages, structured subjective cognitive assessment may be beneficial to identify the early signs of cognitive impairment, and subsequently allow for earlier interventions to maintain cognitive performance as these adults continue to survive into old age.

Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial.

PubMed

Fox, Julie; Peters, Barry; Prakash, Manyu; Arribas, Jose; Hill, Andrew; Moecklinghoff, Christiane

2011-01-01

Low levels of vitamin D are reported in HIV-infected individuals. In HIV-negative people, low vitamin D levels have been associated with an increased risk of cardiovascular disease and cancer and with worse survival. The MONET trial recruited 256 European patients with HIV RNA <50 copies/ml at screening, while taking either NNRTI- or PI-based HAART. Patients were switched to DRV/r 800/100 mg once daily, either as monotherapy or with two NRTIs. In all, 221 patients were measured for 25-hydroxyvitamin D at a central laboratory before randomized treatment started and at week 96. Multiple regression was used to correlate vitamin D levels with gender, season, ethnic group, treatment group, and use of antiretrovirals. Overall, 80% of patients were male and 91% were white, with a mean age of 44 years. At screening, 170/221 (77%) patients had vitamin D deficiency (<50 nmol/liter). At the screening visit, lower vitamin D levels were significantly associated with calendar month (p = 0.0067), black ethnicity (p = 0.013), use of efavirenz (p = 0.0062), and use of zidovudine (p = 0.015). Mean vitamin D levels were lowest from January to April (mean = 35.8 nmol/liter) and highest in September (mean = 45.4 nmol/liter). Increases in vitamin D between screening and week 96 were significantly greater for patients who discontinued efavirenz or zidovudine before the MONET trial versus those who stopped other antiretrovirals. At screening, lower vitamin D levels were associated with season, race, and use of efavirenz and/or zidovudine. Switching from efavirenz and/or zidovudine to darunavir/ritonavir during the trial led to increases in vitamin D levels. Routine screening of HIV-positive patients for vitamin D should be considered and the optimal management further defined.

Factors influencing adherence to antiretroviral treatment in Nepal: a mixed-methods study.

PubMed

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

2012-01-01

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. 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. 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. Improving adherence requires a supportive environment; accessible treatment; clear instructions about regimens; and regimens

Barriers to and facilitators of HIV-positive patients' adherence to antiretroviral treatment regimens.

PubMed

Roberts, K J

2000-03-01

HIV-positive patients must strictly adhere to antiretroviral regimens for the medications to work properly. Little, however, is known about the obstacles that patients face in adhering to the regimens or what, if anything, helps patients to adhere. The goals of the project were to describe, from HIV-positive patients' own perspectives, the barriers they face in adhering to antiretroviral regimens and the strategies they use to maximize their adherence. Five main barriers (forgetfulness, social/physical environment, complexity of the regimens, medication side effects, and inadequate patient knowledge) to adherence and six main facilitators (mechanical devices, "making a commitment," "routinizing," health beliefs, social support, and professional support) emerged from the data. Patients may overcome some of these barriers by receiving better health education about the need for adherence, professional and lay support for their efforts, and mechanical devices such as alarm clocks and medi-sets. Other barriers, however, such as the complexity of the medications, highlight the need for simplified antiretroviral regimens.

Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

PubMed Central

Peterson, Kevin; Jallow, Sabelle; Rowland-Jones, Sarah L.; de Silva, Thushan I.

2011-01-01

HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations. PMID:21490779

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

PubMed

Sudfeld, Christopher R; Mugusi, Ferdinand; Aboud, Said; Nagu, Tumaini J; Wang, Molin; Fawzi, Wafaie W

2017-02-10

HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D 3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D 3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D 3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D 3 regimen consists of oral supplements containing 50,000 IU vitamin D 3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D 3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D 3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. The ToV4 will provide causal evidence on the effect of vitamin D 3 supplementation on incidence of

Impact of use of alcohol and illicit drugs by AIDS patients on adherence to antiretroviral therapy in Bahia, Brazil.

PubMed

Teixeira, Celia; Dourado, Maria De Lourdes; Santos, Marcio P; Brites, Carlos

2013-05-01

Use of alcohol and illicit drugs is a common finding among HIV-infected individuals, but there are many open questions about its impact on adherence to antiretroviral therapy and virological outcomes. Our study aimed to evaluate the impact of the use of alcohol and illicit drugs on the adherence to antiretroviral therapy (ART) among patients starting ART in Salvador, Brazil. We followed up 144 AIDS patients initiating ART for a 6-month period. At baseline, they were interviewed about demographics, behavior, and use of illicit drugs and alcohol. All of them had HIV-1 RNA plasma viral load and CD4(+)/CD8(+) cells count measured before starting therapy. After 60 days of treatment they were asked to answer a new questionnaire on adherence to ART. All patients were monitored during the following months, and new CD4(+) cell count/HIV-1 RNA plasma viral load determinations were performed after 6 months of therapy. Optimal adherence to therapy was defined by self-reported questionnaire, by 95% use of prescribed drug doses, and by using plasma HIV-1 RNA viral load as a biological marker. A total of 61 (42.4%) patients reported alcohol use, 7 (4.9%) used illicit drugs, and 17 (11.8%) used both alcohol and illicit drugs. Being in a steady relationship was protective to nonadherence (95% CI: 0.18-0.84). Missing more than two medical visits was also associated with a 68% higher likelihood of nonadherence (95% CI: 0.10-1.02). After logistic regression we detected a higher risk of nonadherence for patients declaring use of alcohol plus illicit drugs (odds ratio=6.0; 95% CI: 1.78-20.28) or high-intensity use of alcohol (odds ratio=3.29; 95% CI: 1.83-5.92). AIDS patients using alcohol and/or illicit drugs are socially vulnerable, and need specific and flexible programs, combining mental health care, harm reduction strategies, and assisted drug therapy to maximize the chances of successful use of ART.

Gender differences in clinical, immunological, and virological outcomes in highly active antiretroviral-treated HIV–HCV coinfected patients

PubMed Central

Emery, Joel; Pick, Neora; Mills, Edward J; Cooper, Curtis L

2010-01-01

Objective: The influence of biological sex on human immunodeficiency virus (HIV) antiretroviral treatment outcome is not well described in HIV–hepatitis C (HCV) coinfection. Methods: We assessed patients’ clinical outcomes of HIV–HCV coinfected patients initiating antiretroviral therapy attending the Ottawa Hospital Immunodeficiency Clinic from January 1996 to June 2008. Results: We assessed 144 males and 39 females. Although similar in most baseline characteristics, the CD4 count was higher in females (375 vs 290 cells/μL). Fewer females initiated ritonavir-boosted regimens. The median duration on therapy before interruption or change was longer in males (10 versus 4 months) (odds ratio [OR] 1.40 95% confidence interval: 0.95–2.04; P = 0.09). HIV RNA suppression was frequent (74%) and mean CD4 count achieved robust (over 400 cells/μL) at 6 months, irrespective of sex. The primary reasons for therapy interruption in females and males included: gastrointestinal intolerance (25% vs 19%; P = 0.42); poor adherence (22% vs 15%; P = 0.31); neuropsychiatric symptoms (19% vs 5%; P = 0.003); and lost to follow-up (3% vs 13%; P = 0.08). Seven males (5%) and no females discontinued therapy for liver-specific complications. Death rate was higher in females (23% vs 7%; P = 0.003). Conclusion: There are subtle differences in the characteristics of female and male HIV–HCV coinfected patients that influence HIV treatment decisions. The reasons for treatment interruption and change differ by biological sex. This knowledge should be considered when starting HIV therapy and in efforts to improve treatment outcomes. PMID:20517470

CROI 2017: Advances in Antiretroviral Therapy

PubMed Central

Jones, Joyce; Taylor, Barbara S.; Tieu, Hong-Van; Wilkin, Timothy J.

2017-01-01

The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind. Innovative strategies to improve outcomes include 2-way text messaging, home-based HIV testing, peer navigation, and New York City's realignment of services into comprehensive sexual health programs. A high prevalence of resistance was documented in low- and middle-income settings and policy considerations were modeled to address increasing resistance rates. Novel resistance mutations to integrase strand transfer inhibitors and nucleoside analogue reserve transcriptase inhibitors were identified, but the clinical implications are unclear and require further investigation. Several studies provided insights on dosing and safety of antiretroviral therapy to prevent mother-to-child transmission through pharmacokinetic analysis. A special session devoted to Zika virus included a study of its effects on the central nervous system and a promising animal study of a Zika vaccine. PMID:28598790

Interruption of antiretroviral therapy is associated with increased plasma cystatin C.

PubMed

Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda; Neuhaus, Jacquie; El-Sadr, Wafaa; Tracy, Russell; Kuller, Lewis; Shlipak, Michael; Angus, Brian; Klinker, Harting; Ross, Michael

2009-01-02

Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.

Factors influencing antiretroviral treatment suboptimal adherence among perinatally HIV-infected adolescents in Thailand

PubMed Central

Munir, Kerim; Kanabkaew, Cheeraya; Le Coeur, Sophie

2017-01-01

Background Existing studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children. Methods We used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12–19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010–2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART. Results From the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor. Conclusion Our findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in

Management of common adverse effects in the era of highly active antiretroviral therapy in south east Ethiopia

PubMed Central

Abdella, Sadikalmahdi Hussen; Wabe, Nasir Tajure; Yesuf, Elias Ali

2011-01-01

Background: The combination of antiretroviral therapy is the corner stone of management of patients with human immune deficiency virus infection. Although antiretroviral therapy can reduce viral load to undetectable level, improve the immunity and prolong survival of patients, antiretroviral drugs are associated with many adverse effects that may be severe and affect patient adherence and quality of life. Aims: The aim of this study was to assess management strategies under taken in patient's experienced common adverse effects of highly active antiretroviral therapy in Goba Hospital antiretroviral clinic. Patients and Methods: A cross sectional study of patient record chart of patients who had follow-up during data collection period was done followed by patient interview. Data was filled on well structured questionnaire and analyzed using SPSS for window version 16.0. Results: The common adverse effects were Rash (48.8%), Peripheral neuropathy (36.9%) and Anemia (20.24%). The rate of management was 39.3%. Pyridoxine (36.8%) was commonly prescribed drug for management of Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs for management of Rash and Anemia respectively. Use of traditional healers (57.7%) was leading reason for non-management. Conclusion: Rate of management for common adverse effect is low. Education should be given on adverse effects for patients. PMID:22361495

Evaluation of the Monongalia County Schools, Even Start Family Literacy Program. Monongalia County Even Start Program. Parents Are Their Children's First and Most Important Teachers.

ERIC Educational Resources Information Center

Meehan, Merrill L.

The Monongalia County (West Virgina) Even Start Program begun in 1993 to address family literacy and to prepare children for entrance into school, consists of three interrelated approaches: adult education, parenting education, and early childhood education. In June 1996, the program was serving 62 families (mostly low-income) with an average of…

The antiretrovirals in pregnancy registry: a fifteenth anniversary celebration.

PubMed

Tilson, Hugh H; Doi, Peggy A; Covington, Deborah L; Parker, Artist; Shields, Kristine; White, Alice

2007-02-01

The year 2007 marks the fifteenth anniversary year of the founding of a landmark effort in drug safety risk management, the formation of the first monitoring effort of an antiretroviral (ARV) drug in pregnancy which has become the Antiretrovirals in Pregnancy Registry, the APR. This multicompany, multi-national voluntary collaborative registry monitors pregnancy exposure to a class of highly important drugs for any indication of an increase in the postexposure incidence of birth defects in the offspring of these pregnancies. To recognize the anniversary, the Steering Committee of the APR has commissioned this review of the contributions and lessons learned over the past decade and a half and, in the spirit of continuous process improvement, has committed to apply these lessons for the next fifteen years. This retrospective examines the antecedents to this registry and the context in which the APR was formed; the early efforts to establish technical and organizational procedures and policies; the evolving experiences with enrollment and follow-up, patient and participant protections, information management and oversight; public and regulatory dissemination; and of course, the accomplishments and lessons learned. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to explain the value of a drug registry in determining safety risk management; summarize that the Antiretroviral (ARV) drugs in Pregnancy Registry (APR) is a very successful multinational, multicompany collaborative effort that has been in place for 15 years; and state that it has been an ideal public interest effort dealing with the devastating pandemic of human immunodeficiency viral disease.

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

Metabolic disorders and cardiovascular risk in people living with HIV/AIDS without the use of antiretroviral therapy.

PubMed

Raposo, Mariana Amaral; Armiliato, Geyza Nogueira de Almeida; Guimarães, Nathalia Sernizon; Caram, Camila Abrahão; Silveira, Raíssa Domingues de Simoni; Tupinambás, Unaí

2017-01-01

Metabolic disorders in people living with HIV/AIDS (PLH) have been described even before the introduction of antiretroviral (ARV) drugs in the treatment of HIV infection and are risk factors for cardiovascular diseases. Based on this, the purpose of this study was to assess metabolic disorders and cardiovascular risk in PLH before the initiation of antiretroviral treatment (ART). This was a cross-sectional descriptive study of 87 PLH without the use of ART, which was carried out between January and September 2012 at a specialized infectious diseases center in Minas Gerais, Brazil. The main metabolic disorders in the population were low serum levels of HDL-cholesterol, hypertriglyceridemia and abdominal obesity. Dyslipidemia was prevalent in 62.6% of the study population, whereas metabolic syndrome (MS) was prevalent in 11.5% of patients assessed by the International Diabetes Federation (IDF) criteria and 10.8% assessed by the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII) criteria. Regarding cardiovascular risk, 89.7% of the population presented a low coronary risk according to the Framingham Risk Score. A greater proportion of patients diagnosed with MS presented low cardiovascular risk (80% assessed by IDF criteria and 77.8% assessed by NCEP-ATPIII criteria). Metabolic disorders in this population may be due to HIV infection or lifestyle (smoking, sedentary lifestyle and inadequate diet). The introduction of ART can enhance dyslipidemia, increasing cardiovascular risk, especially among those who have classic risks of cardiovascular disease.

PKC-mediated HuD-GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy.

PubMed

Sanna, M D; Quattrone, A; Ghelardini, C; Galeotti, N

2014-03-01

Patients treated with nucleoside reverse transcriptase inhibitors (NRTIs) develop painful neuropathies that lead to discontinuation of antiretroviral therapy thus limiting viral suppression strategies. The mechanisms by which NRTIs contribute to the development of neuropathy are not known. In order to elucidate the mechanisms underlying this drug-induced neuropathy, we have characterized cellular events in the central nervous system following antiretroviral treatment. Systemic administration of the antiretroviral agent, 2',3'-dideoxycytidine (ddC) considerably increased the expression and phosphorylation of protein kinase C (PKC) γ and ɛ, enzymes highly involved in pain processes, within periaqueductal grey matter (PAG), and, to a lesser extent, within thalamus and prefrontal cortex. These events appeared in coincidence with thermal and mechanical allodynia, but PKC blockade did not prevent the antiretroviral-induced pain hypersensitivity, ruling out a major involvement of PKC in the ddC-induced nociceptive behaviour. An increased expression of GAP43, a marker of neuroregeneration, and decreased levels of ATF3, a marker of neuroregeneration, were detected in all brain areas. ddC treatment also increased the expression of HuD, a RNA-binding protein target of PKC known to stabilize GAP43 mRNA. Pharmacological blockade of PKC prevented HuD and GAP43 overexpression. Silencing of both PKCγ and HuD reduced GAP43 levels in control mice and prevented the ddC-induced GAP43 enhanced expression. Present findings illustrate the presence of a supraspinal PKC-mediated HuD-GAP43 pathway activated by ddC. Based on our results, we speculate that antiretroviral drugs may recruit the HuD-GAP43 pathway, potentially contributing to a response to the antiretroviral neuronal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-01-02

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

Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

PubMed

Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

2015-03-01

We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics

PubMed Central

Shah, Ankit; Gangwani, Mohitkumar R.; Chaudhari, Nitish S.; Glazyrin, Alexy; Bhat, Hari K.; Kumar, Anil

2016-01-01

Despite the advent of highly active antiretroviral therapy (HAART), HIV-associated neurological disorders (HAND) remain a major challenge in human immunodeficiency virus (HIV) treatment. The early implementation of HAART in the infected individuals helps suppress the viral replication in the plasma and other compartments. Several studies also report the beneficial effect of drugs that successfully penetrate central nervous system (CNS). However, recent data in both clinical setup and in in vitro studies indicate CNS toxicity of the antiretrovirals (ARVs). Although the evidence is limited, correlation between prolonged use of ARVs and neurotoxicity strongly suggests that it is essential to study the underlying mechanisms responsible for such toxicity. Furthermore, closer attention toward clinical outcomes is required to screen various ARV regimens for their association with HAND and other comorbidities. A growing body of literature also indicates a possible role of accelerated aging in the antiretroviral therapy-associated neurotoxicity. Lastly, owing to high pill burden, multiple drugs in the HIV treatment also invite a possible role of drug–drug interaction via various cytochrome P450 enzymes. The particular emphasis of this review is to highlight the need to identify alternative approaches in reducing the CNS toxicity of the ARV drugs in HIV-infected individuals. PMID:27364698

Associations between vitamin D metabolites, antiretroviral therapy and bone mineral density in people with HIV.

PubMed

Klassen, K M; Kimlin, M G; Fairley, C K; Emery, S; Anderson, P H; Ebeling, P R

2016-05-01

To see if vitamin D and antiretroviral therapy are associated with bone mineral density (BMD) in people with HIV. Lower hip BMD was associated with tenofovir (an antiretroviral medicine) in those with 25(OH)D ≥50 nmol/L. The relationship between antiretroviral therapy and hip BMD differs depending on vitamin D status. People with HIV have an increased risk of low BMD and fractures. Antiretroviral therapy contributes to this increased risk. The aim of this study was to evaluate associations between vitamin D metabolites and antiretroviral therapy on BMD. The simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine trial (STEAL) was an open-label, prospective randomised non-inferiority study that compared simplification of current nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose combination tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine. Serum 25(OH)D and 1,25(OH)2D were measured in 160 individuals (90 receiving TDF-FTC, 70 receiving other NRTIs) at baseline from this study. Multivariable linear regression models were constructed to evaluate the covariates of 1,25(OH)2D and BMD. Protease inhibitor use (p = 0.02) and higher body mass index (BMI) (p = 0.002) were associated with lower 1,25(OH)2D levels in those with 25(OH)D <50 nmol/L. However, TDF-FTC use (p = 0.01) was associated with higher 1,25(OH)2D levels, but only in those with 25(OH)D ≥50 nmol/L. White ethnicity (p = 0.02) and lower BMI (p < 0.001) in those with 25(OH)D <50 nmol/L and with TDF-FTC use (p = 0.008) in those with 25(OH)D ≥50 nmol/L were associated with lower hip BMD. TDF-FTC use, higher serum calcium and serum βCTX, winter, and lower bone-specific alkaline phosphatase (BALP) and BMI were associated with lower lumbar spine BMD. TDF-FTC use (versus non-TDF-FTC use) was associated with lower hip BMD, and this difference was more pronounced in those with 25(OH)D ≥50 nmol/L. Serum 25(OH)D <50�

Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients.

PubMed

de Mendoza, Carmen; Garrido, Carolina; Corral, Angelica; Ramírez-Olivencia, German; Jiménez-Nacher, Inmaculada; Zahonero, Natalia; Gonzalez-Lahoz, Juan; Soriano, Vincent

2007-07-01

Surveillance of drug resistance mutations in antiretroviral-experienced HIV(+) patients may provide useful information regarding options available for rescue interventions. All resistance tests performed from 1999 to 2005 on antiretroviral-experienced individuals at one reference laboratory in Madrid were examined. Only mutations associated with drug resistance recorded at the September 2006 IAS-USA list were considered. A total of 2137 specimens were analyzed. Overall, 71.1% showed resistance mutations to at least one drug class, 56.1% to at least two, and 21% to all three drug families. Resistance mutations were 65% for NRTI, 44.4% for NNRTI, and 42.5% for PI. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. Their rate significantly declined since 1999. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). The presence of five or more was 58.8% in 1999 but declined to 22.2% in 2005. The rate of drug resistance mutations causing NRTI and PI resistance has steadily declined in antiretroviral-experienced patients since 1999. The availability of a large number and/or more convenient NRTI as well as the wide use of ritonavir-boosted PI could explain these observations. However, broad PI cross-resistance was seen in nearly 25% of antiretroviral-experienced patients in 2005. Therefore, there is a still need for new antiretrovirals with different resistance profiles.

Cost Effectiveness Analysis of Clinically Driven versus Routine Laboratory Monitoring of Antiretroviral Therapy in Uganda and Zimbabwe

PubMed Central

Medina Lara, Antonieta; Kigozi, Jesse; Amurwon, Jovita; Muchabaiwa, Lazarus; Nyanzi Wakaholi, Barbara; Mujica Mota, Ruben E.; Walker, A. Sarah; Kasirye, Ronnie; Ssali, Francis; Reid, Andrew; Grosskurth, Heiner; Babiker, Abdel G.; Kityo, Cissy; Katabira, Elly; Munderi, Paula; Mugyenyi, Peter; Hakim, James; Darbyshire, Janet; Gibb, Diana M.; Gilks, Charles F.

2012-01-01

Background Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated. Methods Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial. Results 3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm3) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term. Conclusions There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African

Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

PubMed

Kantor, Rami; Katzenstein, David A; Efron, Brad; Carvalho, Ana Patricia; Wynhoven, Brian; Cane, Patricia; Clarke, John; Sirivichayakul, Sunee; Soares, Marcelo A; Snoeck, Joke; Pillay, Candice; Rudich, Hagit; Rodrigues, Rosangela; Holguin, Africa; Ariyoshi, Koya; Bouzas, Maria Belen; Cahn, Pedro; Sugiura, Wataru; Soriano, Vincent; Brigido, Luis F; Grossman, Zehava; Morris, Lynn; Vandamme, Anne-Mieke; Tanuri, Amilcar; Phanuphak, Praphan; Weber, Jonathan N; Pillay, Deenan; Harrigan, P Richard; Camacho, Ricardo; Schapiro, Jonathan M; Shafer, Robert W

2005-04-01

The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

Macronutrient supplementation for malnourished HIV-infected adults: a review of the evidence in resource-adequate and resource-constrained settings.

PubMed

Koethe, John R; Chi, Benjamin H; Megazzini, Karen M; Heimburger, Douglas C; Stringer, Jeffrey S A

2009-09-01

Access to antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has expanded rapidly throughout sub-Saharan Africa, but malnutrition and food insecurity have emerged as major barriers to the success of ART programs. Protein-calorie malnutrition (a common form of malnutrition in the region) hastens HIV disease progression, and food insecurity is a barrier to medication adherence. Analyses of patient outcomes have identified a low body mass index after the start of ART as an independent predictor of early mortality, but the causes of a low body mass index are multifactorial (eg, normal anthropometric variation, chronic inadequate food intake, and/or wasting associated with HIV infection and other infectious diseases). Although there is much information on population-level humanitarian food assistance, few data exist to measure the effectiveness of macronutrient supplementation or to identify individuals most likely to benefit. In this report, we review the current evidence supporting macronutrient supplementation for HIV-infected adults, we report on clinical trials in resource-adequate and resource-constrained settings, and we highlight priority areas for future research.

Predictors of attrition from care at 2 years in a prospective cohort of HIV-infected adults in Tigray, Ethiopia

PubMed Central

Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Fucili, Luca; Gregorio, Massimiliano Di; Mirra, Marco; Castro, Paola De; Terlizzi, Roberta; Tatarelli, Paola; Binelli, Andrea; Zegeye, Teame; Campagnoli, Michela; Vella, Stefano; Abraham, Loko; Godefay, Hagos

2017-01-01

Introduction Ethiopia has experienced rapid expansion of antiretroviral therapy (ART). However, as long-term retention in ART therapy is key for ART effectiveness, determinants of attrition need to be identified so appropriate interventions can be designed. Methods We used data from the ‘Cohort of African people Starting Antiretroviral therapy’ (CASA) project, a prospective study of a cohort of HIV-infected patients who started ART in seven health facilities (HFs). We analysed the data of patients who had started first-line ART between January 2013 and December 2014. The Kaplan–Meier method was used to estimate the probability of retention at different time points. The Cox proportional hazards model was used to identify factors associated with attrition. Results A total of 1198 patients were included in the study. Kaplan–Meier estimates of retention in care were 83.9%, 82.1% and 79.8% at 12, 18 and 24 months after starting ART, respectively. Attrition was mainly due to loss to follow-up, transferred-out patients and documented mortality. A multivariate Cox proportional hazard model showed that male sex, CD4 count <200 cells/µL and the type of HF were significantly associated with attrition. Conclusions The observed attrition differences according to gender suggest that separate interventions designed for women and men should be explored. Moreover, innovative strategies to increase HIV testing should be supported to avoid CD4 levels falling too low, a factor significantly associated with higher attrition in our study. Finally, specific studies to analyse the reasons for different levels of attrition among HFs are required. PMID:29082011

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS

PubMed Central

Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

2013-01-01

Introduction There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was −2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p≤0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤−3 was a strong predictor associated with a 5.59 times risk of severe

Benefits of combined preventive therapy with co-trimoxazole and isoniazid in adults living with HIV: time to consider a fixed-dose, single tablet coformulation.

PubMed

Harries, Anthony D; Lawn, Stephen D; Suthar, Amitabh B; Granich, Reuben

2015-12-01

Antiretroviral therapy (ART) is the main intervention needed to reduce morbidity and mortality and to prevent tuberculosis in adults living with HIV. However, in most resource-limited countries, especially in sub-Saharan Africa, ART is started too late to have an effect with substantial early morbidity and mortality, and in high tuberculosis burden settings ART does not reduce the tuberculosis risk to that reported in individuals not infected with HIV. Co-trimoxazole preventive therapy started before or with ART, irrespective of CD4 cell count, reduces morbidity and mortality with benefits that continue indefinitely. Isoniazid preventive therapy as an adjunct to ART prevents tuberculosis in high-exposure settings, with long-term treatment likely to be needed to sustain this benefit. Unfortunately, both preventive therapies are underused in low-income and high-burden settings. ART development has benefited from patient-centred simplification with several effective regimens now available as a one per day pill. We argue that co-trimoxazole and isoniazid should also be combined into a single fixed-dose pill, along with pyridoxine (vitamin B6), that would be taken once per day to help with individual uptake and national scale-up of therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins.

PubMed

Allen, Lindsay H; Hampel, Daniela; Shahab-Ferdows, Setareh; York, Emily R; Adair, Linda S; Flax, Valerie L; Tegha, Gerald; Chasela, Charles S; Kamwendo, Debbie; Jamieson, Denise J; Bentley, Margaret E

2015-12-01

Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation. The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi. Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum. Women were assigned to receive antiretrovirals and LNSs, antiretrovirals only, LNSs only, or a control. Antiretrovirals and LNSs were given to the mothers from weeks 0 to 28. The antiretrovirals were zidovudine/lamivudine and nelfinavir or lopinavir/ritonavir. LNSs provided 93-118% of the Recommended Dietary Allowances of thiamin, riboflavin, niacin, pyridoxine, and vitamin B-12. Infants were exclusively breastfed. LNSs increased milk concentrations of all vitamins except thiamin, whereas antiretrovirals lowered concentrations of nicotinamide, pyridoxal, and vitamin B-12. Although antiretrovirals alone had no significant effect on riboflavin concentrations, they negatively affected the LNS-induced increase in this vitamin. Thiamin was not influenced by the study interventions. Concentrations of all B vitamins were much lower than usually accepted values. All B vitamins were low in milk, and all but thiamin were increased by maternal supplementation with LNSs. Antiretrovirals alone decreased concentrations of some B vitamins in milk. When LNS was given in addition to antiretrovirals, the negative effect of antiretrovirals offset the positive effect of LNSs for all vitamins except thiamin. This trial was registered at clinicaltrials.gov as NCT00164762. © 2015 American Society for Nutrition.

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

PubMed

Maganda, Betty A; Minzi, Omary M S; Kamuhabwa, Appolinary A R; Ngasala, Billy; Sasi, Philip G

2014-05-30

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. 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. 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 < 0.001). In all three arms, the

Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment

PubMed Central

Bor, Jacob; Herbst, Abraham J; Newell, Marie-Louise; Bärnighausen, Till

2013-01-01

The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000–2011. In 2003, the year before ART became available in the public sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years – an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for investment decisions of individuals, governments, and donors. PMID:23430655

Predictors of CD4:CD8 ratio normalization and its effect on health outcomes in the era of combination antiretroviral therapy.

PubMed

Leung, Victor; Gillis, Jennifer; Raboud, Janet; Cooper, Curtis; Hogg, Robert S; Loutfy, Mona R; Machouf, Nima; Montaner, Julio S G; Rourke, Sean B; Tsoukas, Chris; Klein, Marina B

2013-01-01

HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death. A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000-2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥ 1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models. 4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm(3), baseline CD8+ T-cells <500 cells/mm(3), time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death. In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.

Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)–Associated Tuberculous Meningitis

PubMed Central

Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James

2015-01-01

Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680

Changes in Body Fat Distribution on Dual-Energy X-Ray Absorptiometry in Black South Africans Starting First-Line Antiretroviral Therapy.

PubMed

Abrahams, Zulfa; Levitt, Naomi; Lesosky, Maia; Maartens, Gary; Dave, Joel

2016-10-01

Long-term use of antiretroviral therapy (ART) increases the risk of developing lipodystrophy. Few studies from Africa have used longitudinal data to assess the development of lipoatrophy and lipohypertrophy. We use clinical anthropometry and dual-energy X-ray absorptiometry (DEXA) to describe changes in body fat distribution over a 24-month period in individuals initiated on ART. A convenience sample of black South Africans (55 men and 132 women) were recruited and followed for 24 months after commencing ART. Body fat distribution was assessed using anthropometric measurements and DEXA scans at baseline and then at 3, 6, 12, 18, and 24 months after commencing ART. DEXA was also used to estimate abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Women gained more overall weight and more regional fat in all areas analyzed on DEXA scans. Women, not men, experienced a significant increasing trend in trunk fat and a significant decreasing trend in limb fat, when expressed as a percentage of total body fat. In men, the risk of developing lipoatrophy was more than two times greater than that of women, after adjusting for age, baseline body mass index, and ART regimen. Lipohypertrophy occurred similarly in men and women. VAT and SAT increased significantly in men and women, with women gaining considerably more than men. These findings are of great concern as an increased waist circumference is associated with increased mortality in HIV-infected populations. Further investigation is required to understand the mechanisms underlying the sex differences in changes in body fat distribution and its effects on cardiovascular risk.

Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey.

PubMed

Ávila-Ríos, Santiago; García-Morales, Claudia; Matías-Florentino, Margarita; Romero-Mora, Karla A; Tapia-Trejo, Daniela; Quiroz-Morales, Verónica S; Reyes-Gopar, Helena; Ji, Hezhao; Sandstrom, Paul; Casillas-Rodríguez, Jesús; Sierra-Madero, Juan; León-Juárez, Eddie A; Valenzuela-Lara, Marisol; Magis-Rodríguez, Carlos; Uribe-Zuñiga, Patricia; Reyes-Terán, Gustavo

2016-12-01

WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods. Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9·4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression. Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15·5%, 95% CI 11·4-20·5) had pretreatment resistance to any antiretroviral drug and 28 (10·6%, 7·2-15·0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score ≥15) was noted in 13 (4 · 9%) of participants to efavirenz and in 23 (8·7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14·4%, 95% CI 10·4-19·2) had pretreatment resistance to any antiretroviral drug and 26 (9·8%, 6·5

Later Start, Longer Sleep: Implications of Middle School Start Times.

PubMed

Temkin, Deborah A; Princiotta, Daniel; Ryberg, Renee; Lewin, Daniel S

2018-05-01

Although adolescents generally get less than the recommended 9 hours of sleep per night, research and effort to delay school start times have generally focused on high schools. This study assesses the relation between school start times and sleep in middle school students while accounting for potentially confounding demographic variables. Seventh and eighth grade students attending 8 late starting schools (∼8:00 am, n = 630) and 3 early starting schools (∼7:23 am, n = 343) from a diverse suburban school district completed online surveys about their sleep behaviors. Doubly robust inverse probability of treatment weighted regression estimates of the effects of later school start time on student bedtimes, sleep duration, and daytime sleepiness were generated. Attending a school starting 37 minutes later was associated with an average of 17 additional minutes of sleep per weeknight, despite an average bedtime 15 minutes later. Students attending late starting schools were less sleepy than their counterparts in early starting schools, and more likely to be wide awake. Later school start times were significantly associated with improved sleep outcomes for early adolescents, providing support for the movement to delay school start times for middle schools. © 2018, American School Health Association.

Antiretroviral therapy-induced mitochondrial toxicity: potential mechanisms beyond polymerase-γ inhibition.

PubMed

Selvaraj, S; Ghebremichael, M; Li, M; Foli, Y; Langs-Barlow, A; Ogbuagu, A; Barakat, L; Tubridy, E; Edifor, R; Lam, W; Cheng, Y-C; Paintsil, E

2014-07-01

We hypothesized that competition between nucleotide reverse-transcriptase inhibitor triphosphate and endogenous deoxyribonucleotide triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of polymerase-γ (pol-γ) inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected patients with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median values for the RN pools were 10,062 (interquartile range (IQR): 7,090-12,590), 4,360 (IQR: 3,058-6,838), and 2,968 (IQR: 2,538-4,436) pmol/10(6) cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mitochondrial DNA copy number as compared with negative controls (P < 0.05). Moreover, cases had significantly higher expression levels of pol-γ, nucleotide transporters, cellular kinases, and adenosine triphosphate (ATP)-binding cassette (ABC) proteins as compared with controls. Antiretroviral therapy (ART) perturbs RN and dRN pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of pol-γ inhibition.

Diminishing availability of publicly funded slots for antiretroviral initiation among HIV-infected ART-eligible patients in Uganda.

PubMed

Geng, Elvin H; Bwana, Mwebesa B; Kabakyenga, Jerome; Muyindike, Winnie; Emenyonu, Nneka I; Musinguzi, Nicholas; Mugyenyi, Peter; Martin, Jeffrey N; Bangsberg, David R

2010-11-24

The impact of flat-line funding in the global scale up of antiretroviral therapy (ART) for HIV-infected patients in Africa has not yet been well described. We evaluated ART-eligible patients and patients starting ART at a prototypical scale up ART clinic in Mbarara, Uganda between April 1, 2009 and May 14, 2010 where four stakeholders sponsor treatment - two PEPFAR implementing organizations, the Ugandan Ministry of Health - Global Fund (MOH-GF) and a private foundation named the Family Treatment Fund (FTF). We assessed temporal trends in the number of eligible patients, the number starting ART and tabulated the distribution of the stakeholders supporting ART initiation by month and quartile of time during this interval. We used survival analyses to assess changes in the rate of ART initiation over calendar time. A total of 1309 patients who were eligible for ART made visits over the 14 month period of the study and of these 819 started ART. The median number of ART eligible patients each month was 88 (IQR: 74 to 115). By quartile of calendar time, PEPFAR and MOH sponsored 290, 192, 180, and 49 ART initiations whereas the FTF started 1, 2, 1 and 104 patients respectively. By May of 2010 (the last calendar month of observation) FTF sponsored 88% of all ART initiations. Becoming eligible for ART in the 3(rd) (HR = 0.58, 95% 0.45-0.74) and 4(th) quartiles (HR = 0.49, 95% CI: 0.36-0.65) was associated with delay in ART initiation compared to the first quartile in multivariable analyses. During a period of flat line funding from multinational donors for ART programs, reductions in the number of ART initiations by public programs (i.e., PEPFAR and MOH-GF) and delays in ART initiation became apparent at the a large prototypical scale-up ART clinic in Uganda.

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

PubMed

Chammartin, Frédérique; Zürcher, Kathrin; Keiser, Olivia; Weigel, Ralf; Chu, Kathryn; Kiragga, Agnes N; Ardura-Garcia, Cristina; Anderegg, Nanina; Laurent, Christian; Cornell, Morna; Tweya, Hannock; Haas, Andreas D; Rice, Brian D; Geng, Elvin H; Fox, Matthew P; Hargreaves, James R; Egger, Matthias

2018-06-08

Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/μL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV

PubMed Central

Kahana, Shoshana Y.; Jenkins, Richard A.; Bruce, Douglas; Fernandez, Maria I.; Hightow-Weidman, Lisa B.; Bauermeister, Jose A.

2016-01-01

Background The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States. Methods The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer–assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability). Results Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single

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

PubMed

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

2017-07-20

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had

Systemic and topical drugs for the prevention of HIV infection: antiretroviral pre-exposure prophylaxis

PubMed Central

Baeten, Jared; Celum, Connie

2013-01-01

Pre-exposure prophylaxis (PrEP), in which HIV uninfected persons use oral or topical antiretroviral medications to protect against HIV acquisition, is a promising new HIV prevention strategy. The biologic rationale for evaluation of PrEP for sexual HIV prevention included non-human primate models and antiretroviral prophylaxis for HIV-exposed infants. Proof-of-concept that PrEP protects against sexual HIV acquisition has been demonstrated in four clinical trials, which used the antiretroviral medication tenofovir, either as a vaginal gel or as daily oral tenofovir disoproxil fumarate, alone or co-formulated with emtricitabine. Importantly, however, two trials failed to demonstrate HIV protection with PrEP, with low adherence to daily use of PrEP the leading hypothesis for lack of efficacy. Next steps in the field include rigorous evaluation of uptake and adherence to PrEP in implementation settings and research into ‘next-generation’ PrEP agents with longer half-life and less user-dependence. PMID:23020883

Family matters: Co-enrollment of family members into care is associated with improved outcomes for HIV-infected women initiating antiretroviral therapy.

PubMed

Myer, Landon; Abrams, Elaine J; Zhang, Yuan; Duong, Jimmy; El-Sadr, Wafaa M; Carter, Rosalind J

2014-12-01

Although there is widespread interest in understanding how models of care for delivering antiretroviral therapy (ART) may influence patient outcomes, family-focused approaches have received little attention. In particular, there have been few investigations of whether the co-enrollment of HIV-infected family members may improve adult ART outcomes over time. We examined the association between co-enrollment of HIV-infected family members into care and outcomes of women initiating ART in 12 HIV care and treatment programs across sub-Saharan Africa. Using data from the mother-to-child transmission-(MTCT) Plus Initiative, women starting ART were categorized according to the co-enrollment of an HIV-infected partner and/or HIV-infected child within the same program. Mortality and loss to follow-up were assessed for up to 5 years after women's ART initiation. Of the 2877 women initiating ART included in the analysis, 31% (n = 880) had at least 1 HIV-infected family member enrolled into care at the same program, including 24% (n = 689) who had an HIV-infected male partner, and 10% (n = 295) who had an HIV-infected child co-enrolled. There was no significant difference in the risk of death of women by family co-enrollment status (P = 0.286). However, the risk of loss to follow-up was greatest among women who did not have an HIV-infected family member co-enrolled (19% after 36 months on ART) compared with women who had an HIV-infected family member co-enrolled (3%-8% after 36 months on ART) (P < 0.001). These associations persisted after adjustment for demographic and clinical covariates and were consistent across countries and care programs. These data provide novel evidence for the association between adult outcomes on ART and co-enrollment of HIV-infected family members into care at the same program. Interventions that build on women's family contexts warrant further consideration in both research and policies to promote retention in ART services across sub-Saharan Africa.

Monitoring virologic responses to antiretroviral therapy in HIV-infected adults in Kenya: evaluation of a low-cost viral load assay.

PubMed

Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S; Valentine, Fred

2009-08-28

A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure.

Monitoring Virologic Responses to Antiretroviral Therapy in HIV-Infected Adults in Kenya: Evaluation of a Low-Cost Viral Load Assay

PubMed Central

Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S.; Valentine, Fred

2009-01-01

Background A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. Methodology/Principal Findings We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log10 copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of ≥400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. Conclusion The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure. PMID:19714253

Initiation of antiretroviral therapy in patients with a CD4 count of less than 350 cells: a retrospective audit against key indicators from the CQUIN payment framework.

PubMed

Mercer, R M; Olarinde, O; Ryan, C; Greig, J; Yeeles, H; Walker, A; Walker, H; Meardon, N C

2011-12-01

A proportion of funding for the South Yorkshire HIV Network is dependant on meeting the targets of the Commissioning for Quality and Innovation (CQUIN) payment framework. This states that 85% of patients with a CD4 count below 350 should be on antiretroviral therapy (ART). We also audited how many patients we started on treatment within six weeks. We found 88% of the 243 patients were on ART at the end of the audit, but significantly less had been started on treatment within six weeks of their CD4 count falling below 350. Although the target was achieved, there were patients who should be excluded as shown by other clinical guidelines, for example patients on treatment for tuberculosis. If these patients were excluded and the threshold level increased, it would help emphasize the at-risk patient group and lead to a fairer allocation of funding.

Impact of Risk Factors for Specific Causes of Death in the First and Subsequent Years of Antiretroviral Therapy Among HIV-Infected Patients

PubMed Central

Ingle, Suzanne M.; May, Margaret T.; Gill, M. John; Mugavero, Michael J.; Lewden, Charlotte; Abgrall, Sophie; Fätkenheuer, Gerd; Reiss, Peter; Saag, Michael S.; Manzardo, Christian; Grabar, Sophie; Bruyand, Mathias; Moore, David; Mocroft, Amanda; Sterling, Timothy R.; D'Arminio Monforte, Antonella; Hernando, Victoria; Teira, Ramon; Guest, Jodie; Cavassini, Matthias; Crane, Heidi M.; Sterne, Jonathan A. C.

2014-01-01

Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Methods. Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. Results. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0–1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2–52.7] during the first year of ART and 9.1 [95% CI, 5.8–14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management. PMID:24771333

2007 costs and coverage of antiretrovirals under Medicare Part D for people with HIV/AIDS living in North Carolina.

PubMed

Sengupta, Sohini

2008-01-01

Effective January 1, 2006 Medicare Part D became a new source of prescription drug coverage for people with HIV/AIDS in the United States. The implementation of Part D has affected access to antiretrovirals for people with HIV/AIDS. In North Carolina, access can be difficult because of the state's struggling safety net programs and the growing HIV-infected populations among Blacks and in poor rural counties. This analysis examines Medicare Part D antiretroviral coverage in 2007 for beneficiaries with HIV/AIDS in North Carolina, particularly those who did not qualify as dual eligibles or for a full low-income subsidy. Data describing program coverage were obtained from the Web site www.medicare.gov and descriptive analyses were performed to assess changes in antiretroviral coverage in Part D prescription drug plans in North Carolina. Most of the 26 antiretrovirals are covered in some way by 76 North Carolina prescription drug plans. There may be variability in coverage however associated with (a) antiretroviral classification within formularies; (b) drug premiums; (c) whether premiums can be waived; (d) annual deductibles; and (e) whether coverage is provided in the "doughnut hole." The data may not reflect actual patterns of drug use and realized access to the drugs. The findings are limited to antiretroviral coverage in North Carolina's Part D offerings but could be generalized to other states with similar prescription drug plan costs and coverage. These concerns continue to pose significant challenges to accessing antiretrovirals for Part D beneficiaries with HIV/AIDS in North Carolina. Variability demonstrated within prescription drug plans will continue, and beneficiaries with HIV/AIDS who do not qualify as dual eligibles or for low-income subsidies will need to evaluate these issues when selecting a prescription drug plan in future enrollment periods.

Rates of Initial Virological Suppression and Subsequent Virological Failure After Initiating Highly Active Antiretroviral Therapy: The Impact of Aboriginal Ethnicity and Injection Drug Use

PubMed Central

Martin, L.J.; Houston, S.; Yasui, Y.; Wild, T.C.; Saunders, L.D.

2010-01-01

Objectives: To compare rates of initial virological suppression and subsequent virological failure by Aboriginal ethnicity after starting highly active antiretroviral therapy (HAART). Methods: We conducted a retrospective cohort study of antiretroviral-naïve HIV-patients starting HAART in January 1999-June 2005 (baseline), followed until December 31, 2005 in Alberta, Canada. We compared the odds of achieving initial virological suppression (viral load <500 copies/mL) by Aboriginal ethnicity using logistic regression and, among those achieving suppression, rates of virological failure (the first of two consecutive viral loads > 1000 copies/mL) by Aboriginal ethnicity using cumulative incidence curves and Cox proportional hazards models. Sex, injection drug use as an HIV exposure category (IDU), baseline age, CD4 cell count, viral load, calendar year, and HAART regimen were considered as potential confounders. Results: Of 461 study patients, 37% were Aboriginal and 48% were IDUs; 71% achieved initial virological suppression and were followed for 730.4 person-years. After adjusting for confounding variables, compared to non-Aboriginals with other exposures, the odds of achieving initial virological suppression were lower for Aboriginal IDUs (odds ratio (OR)=0.33, 95% CI=0.19-0.60, p=0.0002), non-Aboriginal IDUs (OR=0.30, 95% CI=0.15-0.60, p=0.0006), and Aboriginals with other exposures (OR=0.38, 95% CI=0.21-0.67, p=0.0009). Among those achieving suppression, Aboriginals experienced higher virological failure rates ≥1 year after suppression (hazard ratio=3.35, 95% CI=1.68-6.65, p=0.0006). Conclusions: Future research should investigate adherence among Aboriginals and IDUs treated with HAART and explore their treatment experiences to assess ways to improve outcomes. PMID:21187007

Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration

PubMed Central

Kantor, Rami; Katzenstein, David A; Efron, Brad; Carvalho, Ana Patricia; Wynhoven, Brian; Cane, Patricia; Clarke, John; Sirivichayakul, Sunee; Soares, Marcelo A; Snoeck, Joke; Pillay, Candice; Rudich, Hagit; Rodrigues, Rosangela; Holguin, Africa; Ariyoshi, Koya; Bouzas, Maria Belen; Cahn, Pedro; Sugiura, Wataru; Soriano, Vincent; Brigido, Luis F; Grossman, Zehava; Morris, Lynn; Vandamme, Anne-Mieke; Tanuri, Amilcar; Phanuphak, Praphan; Weber, Jonathan N; Pillay, Deenan; Harrigan, P. Richard; Camacho, Ricardo; Schapiro, Jonathan M; Shafer, Robert W

2005-01-01

Background The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. Methods and Findings To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Conclusion Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. PMID:15839752

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

PubMed

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

2016-02-01

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

Social, Cultural, and Environmental Challenges Faced by Children on Antiretroviral Therapy in Zimbabwe: a Mixed-Method Study

PubMed Central

Macherera, Margaret; Moyo, Lindani; Ncube, Mkhanyiseli; Gumbi, Angella

2012-01-01

Objectives Despite the advent of antiretroviral therapy (ART), many children, particularly in the rural communities of Zimbabwe, remain vulnerable. The purpose of this study was to determine the factors and challenges facing children on antiretroviral therapy (ART) in Brunapeg area of Mangwe District, Zimbabwe. Methods A mixed-method approach involving interviewer-guided focus group discussions and piloted semi-structured questionnaires was utilized to collect data from different key population groups. The data obtained were analyzed through content coding procedures based on a set of predetermined themes of interest. Results A number of challenges emerged as barriers to the success of antiretroviral therapy for children. Primary care givers were less informed about HIV and AIDS issues for people having direct impact on the success of antiretroviral therapy in children whilst some were found to be taking the antiretroviral drugs meant for the children. It also emerged that some primary care givers were either too young or too old to care for the children while others had failed to disclose to the children why they frequently visited the Opportunistic Infections (OI) clinic. Most primary care givers were not the biological parents of the affected children. Other challenges included inadequate access to health services, inadequate food and nutrition and lack of access to clean water, good hygiene and sanitation. The lack of community support and stigma and discrimination affected their school attendance and hospital visits. All these factors contributed to non-adherence to antiretroviral drugs. Conclusions and Public Health Implications Children on ART in rural communities in Zimbabwe remain severely compromised and have unique problems that need multi-intervention strategies both at policy and programmatic levels. Effective mitigating measures must be fully established and implemented in rural communities of developing countries in the fight for universal

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

PubMed Central

Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

2010-01-01

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes. PMID:21178968

Generic substitution of antiretrovirals: patients' and health care providers' opinions.

PubMed

Kieran, Jennifer A; O'Reilly, Eimear; O'Dea, Siobhan; Bergin, Colm; O'Leary, Aisling

2017-10-01

There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.

Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014-2018.

PubMed

Hill, Andrew; Hill, Teresa; Jose, Sophie; Pozniak, Anton

2014-01-01

In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single-tablet regimens do not expire until after 2026. The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database). Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 - all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 - all people switch from patented to generic drugs when available, after patent expiry (dates shown above). There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises). The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC) (69%), efavirenz (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC) (18%), darunavir (DRV) (21%) and atazanavir (ATV) (16%). The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily) was £1018 per person-year. Costs of patented single-tablet regimens ranged from £5000 to £7500 per person-year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from £425 million in 2014 to £459 m in 2015, £495 m in 2016, £536 m in 2017 and £578 m in 2018. With a 100% switch to generics, total predicted costs were £337 m in 2014, £364 m in 2015, £382 m in 2016, £144 m in 2017 and £169 m in 2018. The total predicted saving over five years from a

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

PubMed

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

2012-08-02

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

Long-term impact of highly active antiretroviral therapy on HIV-related health care costs.

PubMed

Keiser, P; Nassar, N; Kvanli, M B; Turner, D; Smith, J W; Skiest, D

2001-05-01

Highly active antiretroviral therapy (HAART) is associated with decreased opportunistic infections, hospitalization, and HIV-related health care costs over relatively short periods of time. We have previously demonstrated that decreases in total HIV cost are proportional to penetration of protease inhibitor therapy in our clinic. To determine the effects of HAART on HIV health care use and costs over 44 months. A comprehensive HIV service within a Veterans Affairs Medical Center. A cost-effectiveness analysis of HAART. The mean monthly number of hospital days, infectious diseases clinic visits, emergency room visits, non-HIV-related outpatient visits, inpatient costs, and antiretroviral treatment costs per patient were determined by dividing these during the period from January 1995 through June 1998 into four intervals. Viral load tests were available from October 1996. Cost-effectiveness of HAART was evaluated by determining the costs of achieving an undetectable viral load over time. Mean monthly hospitalization and associated inpatient costs decreased and remained low 2 years after the introduction of protease inhibitors (37 hospital days per 100 patients). Total cost decreased from $1905 per patient per month during the first quarter to $1090 per patient per month in the third quarter but increased to $1391 per patient per month in the fourth quarter. Antiretroviral treatment costs increased throughout the entire observation period from $79 per patient per month to $518 per patient per month. Hospitalization costs decreased from $1275 per patient per month in the first quarter to less than $500 per patient per month in each of the third and fourth quarters. The percentage of patients with a viral load <500 copies/mL increased from 21% in October 1996 to 47% in June of 1997 (p =.014). The cost of achieving an undetectable viral load decreased from $4438 per patient per month to $2669 per patient per month, but this trend did not reach statistical significance

High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

PubMed

Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

2009-05-01

To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

Rates and drivers of progression to pre-diabetes and diabetes mellitus among HIV-infected adults on antiretroviral therapy: a global systematic review and meta-analysis protocol.

PubMed

Nansseu, Jobert Richie N; Bigna, Jean Joel R; Kaze, Arnaud D; Noubiap, Jean Jacques N

2016-09-15

With the new 'test and treat' policy of the WHO, it is obvious that the number of HIV-infected patients taking antiretroviral therapy (ART) will grow exponentially, with consequential increase in the burden of diabetes mellitus (DM). Our aim is to summarise existing data on the incidence of pre-diabetes and DM, and associated risk factors among HIV-infected adults. This systematic review will include cohort studies reporting the incidence of pre-diabetes and/or DM, and associated risk factors among HIV-infected adults on ART, with these patients being free of any impaired glucose metabolism at study baseline. We will perform electronic searches in PubMed, Excerpta Medica Database (EMBASE), Web of Science and WHO Global Health Library, supplemented with manual searches. Articles published from 1 January 2000 to 31 July 2016, in English or French languages, and without any geographical restriction will be eligible for inclusion. 3 authors will independently screen, select studies, extract data and assess the risk of bias with discrepancies resolved by consensus. We will assess clinical heterogeneity by examining the study design and setting, criteria and cut-offs used to define pre-diabetes or DM, process of calculation of incidence and outcomes in each study. We will also assess statistical heterogeneity using the χ(2) test of homogeneity and quantify it using the I(2) statistic. A random effects meta-analysis will be used to estimate the overall cumulative incidence of pre-diabetes/DM and risk factors. This systematic review will use data from published studies and does not require ethics approval. Its results are expected to help putting in place action plans and preventive measures to curb the growing burden of DM in the HIV population on ART. Findings will be published in a peer-reviewed journal and presented at scientific conferences. CRD42016039651. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Likelihood of Starting Dialysis after Incident Fistula Creation

PubMed Central

Quinn, Robert R.; Garg, Amit X.; Kim, S. Joseph; Wald, Ron; Paterson, J. Michael

2012-01-01

Summary Background and objectives Guidelines promote early fistula creation to avoid central venous catheter use. This practice may lead to fistula creations in patients who never receive dialysis. The objective of this study was to estimate the risk of fistula nonuse with long-term follow-up. Design, setting, participants, & measurements Administrative health data identified 1929 predialysis adults who had their first fistula creation between April of 2002 and March of 2006. Patients were followed for a minimum of 2 years or until they began dialysis, received a kidney transplant, or died. Results The median follow-up times in patients who started dialysis, died without receiving dialysis, and remained in predialysis were 6.1, 11.5, and 38.7 months, respectively. Eighty-one percent of patients initiated dialysis; 9% of patients died without receiving dialysis, and 10% of patients remained predialysis. Forty percent of patients had their first fistula creation 3–12 months before initiating dialysis (the recommended window). Thirty percent were created within 90 days of starting dialysis; 30% were created more than 1 year before starting dialysis, and 10% were created more than 2 years before starting dialysis. Older patients, females, and patients with less comorbidity were not as likely to initiate dialysis after incident fistula creation. Conclusions Most patients who underwent fistula creation before starting dialysis eventually received dialysis with extended follow-up, but the risk was significantly modified by age, sex, and comorbidity. Many patients had fistula creations earlier or later than recommended. PMID:22344512

Attrition from antiretroviral treatment services among pregnant and non-pregnant patients following adoption of Option B+ in Haiti

PubMed Central

Domercant, Jean Wysler; Puttkammer, Nancy; Young, Paul; Yuhas, Krista; François, Kesner; Grand’Pierre, Reynold; Lowrance, David; Adler, Michelle

2017-01-01

ABSTRACT Background: Access to antiretroviral therapy (ART) has expanded in Haiti because of the adoption of Option B+ and the revision of treatment guidelines. Retention in care and treatment varies greatly and few studies have examined retention rates, particularly among women enrolled in Option B+. Objective: To assess attrition among pregnant and non-pregnant patients initiating ART following adoption of Option B+ in Haiti. Methods: Longitudinal data of adult patients initiated on ART from October 2012 through August 2014 at 73 health facilities across Haiti were analyzed using a survival analysis framework to determine levels of attrition. The Kaplan–Meier method and Cox proportional hazards regression were used to examine risk factors associated with attrition. Results: Among 17,059 patients who initiated ART, 7627 (44.7%) were non-pregnant women, 5899 (34.6%) were men, and 3533 (20.7%) were Option B+ clients. Attrition from the ART program was 36.7% at 12 months (95% CI: 35.9–37.5%). Option B+ patients had the highest level of attrition at 50.4% at 12 months (95% CI: 48.6–52.3%). While early HIV disease stage at ART initiation was protective among non-pregnant women and men, it was a strong risk factor among Option B+ clients. In adjusted analyses, key protective factors were older age (p < 0.0001), living near the health facility (p = 0.04), having another known HIV-positive household member (p < 0.0001), having greater body mass index (BMI) (p < 0.0001), pre-ART counseling (p < 0.0001), and Cotrimoxazole prophylaxis during baseline (p < 0.01). Higher attrition was associated with rapidly starting ART after enrollment (p < 0.0001), anemia (p < 0.0001), and regimen tenofovir+lamivudine+nevirapine (TDF+3TC+NVP) (p < 0.001). Conclusions: ART attrition in Haiti is high among adults, especially among Option B+ patients. Identifying newly initiated patients most at risk for attrition and providing appropriate interventions could help

Hybrid: Starting

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: gray bar STARTING When the vehicle is started, the gasoline engine "warms up." If necessary assists the gasoline engine when additional power is needed. It also acts as a generator, converting also starts the gasoline engine instantly when needed. Main stage: See through car with battery, engine

High uptake of antiretroviral therapy among HIV-positive TB patients receiving co-located services in Swaziland.

PubMed

Pathmanathan, Ishani; Pasipamire, Munyaradzi; Pals, Sherri; Dokubo, E Kainne; Preko, Peter; Ao, Trong; Mazibuko, Sikhathele; Ongole, Janet; Dhlamini, Themba; Haumba, Samson

2018-01-01

Swaziland has the highest adult HIV prevalence and second highest rate of TB/HIV coinfection globally. Recently, the Ministry of Health and partners have increased integration and co-location of TB/HIV services, but the timing of antiretroviral therapy (ART) relative to TB treatment-a marker of program quality and predictor of outcomes-is unknown. We conducted a retrospective analysis of programmatic data from 11 purposefully-sampled facilities to evaluate timely ART provision for HIV-positive TB patients enrolled on TB treatment between July-November 2014. Timely ART was defined as within two weeks of TB treatment initiation for patients with CD4<50/μL or missing, and within eight weeks otherwise. Descriptive statistics were estimated and logistic regression used to assess factors independently associated with timely ART. Of 466 HIV-positive TB patients, 51.5% were male, median age was 35 (interquartile range [IQR]: 29-42), and median CD4 was 137/μL (IQR: 58-268). 189 (40.6%) were on ART prior to, and five (1.8%) did not receive ART within six months of TB treatment initiation. Median time to ART after TB treatment initiation was 15 days (IQR: 14-28). Almost 90% started ART within eight weeks, and 45.5% of those with CD4<50/μL started within two weeks. Using thresholds for "timely ART" according to baseline CD4 count, 73.3% of patients overall received timely ART after TB treatment initiation. Patients with CD4 50-200/μL or ≥200/μL had significantly higher odds of timely ART than patients with CD4<50/μL, with adjusted odds ratios of 11.5 (95% confidence interval [CI]: 5.0-26.6) and 9.6 (95% CI: 4.6-19.9), respectively. TB cure or treatment completion was achieved by 71.1% of patients at six months, but this was not associated with timely ART. This study demonstrates the relative success of integrated and co-located TB/HIV services in Swaziland, and shows that timely ART uptake for HIV-positive TB patients can be achieved in resource-limited, but integrated

Antiretroviral chemoprophylaxis in children and adolescents victims of rape in Abidjan.

PubMed

Ehui, E; Couitchéré, L S; Kouakou, G A; Doumbia, A; Kassi, A N; Mossou, C M; Guié, P Y; Eholié, S

2015-08-01

We described the use of antiretroviral drugs to prevent HIV transmission among children and adolescents victims of rape in Abidjan (Ivory Coast). We conducted a retrospective and descriptive study on children (0-9 years) and adolescents (10-19 years) victims of rape between 2000 and 2013. We analyzed the patients' socio-demographic characteristics and the modality of the chemoprophylaxis. We included 10 children and 89 adolescents in the study. The median age was 16 years old (3-19 years). The median time to consultation was 23.5 hours (5-152 hours). The antiretroviral chemoprophylaxis was administered to 92 patients (93%). No HIV and HBV seroconversion was observed after a 3-month follow-up. A better management of rape victims is required in Abidjan. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

HIV-1 RNA Levels and Antiretroviral Drug Resistance in Blood and Non-Blood Compartments from HIV-1–Infected Men and Women enrolled in AIDS Clinical Trials Group Study A5077

PubMed Central

Kantor, Rami; Bettendorf, Daniel; Bosch, Ronald J.; Mann, Marita; Katzenstein, David; Cu-Uvin, Susan; D’Aquila, Richard; Frenkel, Lisa; Fiscus, Susan; Coombs, Robert

2014-01-01

Background Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study. Methods Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher’s and McNemar’s exact tests to compare VL between sexes and among compartments. Results Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% ‘untreated’ (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects. Conclusions HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

PubMed Central

Davies, Mary-Ann; Phiri, Sam; Wood, Robin; Wellington, Maureen; Cox, Vivian; Bolton-Moore, Carolyn; Timmerman, Venessa; Moultrie, Harry; Ndirangu, James; Rabie, Helena; Technau, Karl; Giddy, Janet; Maxwell, Nicola; Boulle, Andrew; Keiser, Olivia; Egger, Matthias; Eley, Brian

2013-01-01

Background Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. Methodology/Principal Findings Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<−3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. Conclusions/Significance Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve

Investigation of Starting Romantic Intimacy in Emerging Adulthood in Terms of Self-Esteem, Gender and Gender Roles

ERIC Educational Resources Information Center

Eryilmaz, Ali; Atak, Hasan

2011-01-01

This study aims, firstly, to examine whether gender plays a decisive role in starting romantic intimacy during the emerging adulthood period; secondly, to compare emerging adults who are assigned different gender roles, in terms of starting romantic intimacy; and thirdly, to analyze the level at which self-esteem and gender roles predict the…

Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women

PubMed Central

Todd, Jonathan V.; Cole, Stephen R.; Pence, Brian W.; Lesko, Catherine R.; Bacchetti, Peter; Cohen, Mardge H.; Feaster, Daniel J.; Gange, Stephen; Griswold, Michael E.; Mack, Wendy; Rubtsova, Anna; Wang, Cuiwei; Weedon, Jeremy; Anastos, Kathryn; Adimora, Adaora A.

2017-01-01

Abstract Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998–2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women. PMID:28430844

Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.

PubMed

Huntington, Susie; Thorne, Claire; Newell, Marie-Louise; Anderson, Jane; Taylor, Graham P; Pillay, Deenan; Hill, Teresa; Tookey, Pat A; Sabin, Caroline

2015-04-24