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Lack of HIV-1 viral load monitoring in resource-limited settings leads to the development of HIV drug resistance mutations, although WHO recommends viral load testing for monitoring as this helps in preserving future treatment options and also avoid unnecessary switching to more expensive drugs. A total of 101 patients attaining first-line treatment failure (FTF) were followed until second-line treatment failure (STF) to study the rate of accumulation of thymidine analogue mutations (TAMs), their future drug options, and genetic evolution. The result shows that predominant nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations were M184V/I (87.3% in FTF and 79% in STF) followed by TAMs (53.4% in FTF and 54.5% in STF). The rate of accumulation of TAMs was higher for a patient with TAMI [0.015 TAM per person-month (TPPM)], TAMII (0.042 TPPM), and 1 (0.005 TPPM) or 2 TAMs (0.008 TPPM) compared with a patient with both TAMs and 3 or >3 TAMs. Future ART options show that >50% of the patients can be considered for choices to recycle NRTIs in the second-line, and third-line therapy. We conclude that the patients who initiated thymidine analogue-based first-line before 2010 can be very well opted for AZT- and TDF-based second-line regimen in the future.

According to 2013 WHO guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. A total of 167 HIV-1-infected patients attaining immunological failure after TDF-based first-line HAART were included in this study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database were used for mutation interpretation. REGA V3.0 was used for HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). Genotypically predicted level of drug resistance based on mutation pattern shows 88% can be opted for azidothymidine (AZT) and still 65% can be opted for TDF. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself.

Background: Ritonavir-boosted atazanavir (ATV/r) is the preferred second-line protease inhibitor (PI) option for HIV patients in resource-limited settings; its pattern of adverse drug reactions (ADRs) has not been much reported from India; hence, in this study, we have analyzed the incidence of ATV/r-associated ADRs in Southern Indian HIV-1-infected patients., Methods: In this prospective study, 111 HIV patients treated with ATV/r were included with at least 2 years follow-up visits for the emergence of hyperbilirubinemia, hypertransaminasemia, and serum creatinine elevation. The causality assessment was done based on the WHO scale for the causality assessment of suspected ADR., Results: The incidence of severe hyperbilirubinemia, hypertransaminasemia, and creatinine elevation was 28.6, 0.76, and 1.62 cases/100 person years, respectively. 3TC/FTC + TDF (odds ratio [OR]: 6.07, confidence interval [CI]: 1.31-27.98, P = 0.015) nucleos (t) ide reverse transcriptase inhibitor backbone and male sex (OR: 18.64, CI: 2.13-162.93, P = 0.0082) were found to be significantly associated with hypertransaminasemia and creatinine elevation, respectively. The causality assessment of ADR was "possible" for all the participants. Kaplan-Meier analysis showed hyperbilirubinemia to emerge earlier (mean duration: 32.18 months, CI: 24.9-39.4 months) followed by hypertransaminasemia and creatinine elevation. Hyperbilirubinemia is an expected side effect associated with ATV/r which is benign, transient, and does not predispose to hypertransaminasemia., Conclusion: Our study results show that patients starting ATV/r should be counseled for a good adherence in spite of the emergence of hyperbilirubinemia which generally reverts to normal range.

Background: HIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations., Methods: We analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis., Findings: Between Oct 1, 2012, and Dec 19, 2013, we recruited 26,503 participants, 12,022 men who have sex with men and 14,481 people who inject drugs. Median incidence of HIV was 0·87% (IQR 0·40-1·17) in men who have sex with men and 1·43% (0·60-4·00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0·81, 95% CI 0·62-0·91; p<0·0001) than all other measures, although correlation was significant with aware viral load (0·59, 0·27-0·79; p=0·001), population viral load (0·51, 0·16-0·74; p=0·007), and population ART coverage (-0·54, -0·76 to -0·20; p=0·004). In-care viral load was not correlated with HIV incidence (0·29, -0·10 to 0·60; p=0·14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4·34%, and ART use in HIV-positive individuals would need to increase by 19·5%., Interpretation: Prevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme., Funding: US National Institutes of Health, Elton John AIDS Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Drug users (DUs), a population that accounts for some of the fastest-growing human immunodeficiency virus (HIV) epidemics globally, lag behind other populations with regard to HIV-related outcomes. We evaluated the role of voucher incentives on linkage and retention in care among DUs in India., Methods: In this randomized clinical trial, 120 DUs who were aged ≥18 years, HIV-infected, antiretroviral therapy (ART) naive, and ART eligible and who reported drug use in the prior month were randomized to incentive (INC) or control (CTL) conditions for 12 months. Participants randomized to the INC arm received incentives (redeemable for food/household goods) ranging in value from USD4 to USD8 for achieving prespecified targets (eg, ART initiation, visits to ART center). Subjects in the CTL group could win vouchers in prize-bowl drawings, but HIV care behaviors were not incentivized. The primary endpoint was time to ART initiation., Results: Sixty participants each were randomized to the INC and CTL arms between December 2009 and September 2010. Participants in the INC arm were more likely to visit the government ART center (49 vs 33; P = .002); 27 participants in the INC and 16 participants in the CTL arm initiated ART (P = .04; hazard ratio for ART = 2.33 [95% confidence interval, 1.15-4.73]). Participants in the INC arm also had significantly more visits to the ART center (median number of visits, 8 vs 3.5; P = .005). However, no difference in viral suppression was observed., Conclusions: Modest voucher incentives improved linkage to and retention in HIV care, but did not significantly impact viral suppression among DUs in India, a disenfranchised and difficult-to-treat population., Clinical Trials Registration: NCT01031745., (© The Author 2014. 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.)

Long-term follow-up of persons infected with HIV infection is essential to optimize clinical outcomes. However, limited data exist on the rates of dropout (DO) from HIV care and factors associated with DO especially from resource-limited settings. We conducted a retrospective analysis of the data available at YRGCARE, a private HIV care provider in south India that has registered over 15,000 HIV-infected persons since its inception in 1993. We included 7995 patients who registered for care between 1 January 2004 and 31 December 2009. A dropout was defined as a person who registered for care during this period and had not been seen in the clinic for >1 year. Logistic regression was used to examine factors associated with DO from clinical care. The median age of the patients registered for care was 34 years; 66% were male and 83% were married. The overall DO rate was 38.1 per 100 person-years - the majority of the DOs occurred within 6 months from registration. In multivariate analyses, patients who were enrolled in clinical studies/projects entitling them to free medications and retention staff (Odds Ratio [OR]: 0.65) or were on antiretroviral therapy (ART; OR: 0.37) or had a CD4 > 350 at the last visit (OR: 0.20) were significantly less likely to DO from clinical care. We observed a high rate of DO from clinical care at this tertiary HIV clinic in Chennai, India. Making ART available free of charge in the private sector and providing incentives/benefits for attending clinic visits as is routinely done in clinical trials might help improve retention.

Background: The role of T-cell responses against Mycobacterium tuberculosis antigens in tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is unclear., Methods: Peripheral blood mononuclear cells from 45 HIV patients with treated TB, of whom 12 developed TB-IRIS, were collected at weeks 0, 2, and 6 of antiretroviral therapy (ART). Production of interferon-gamma (IFN-γ) and interleukin-2 by T cells after stimulation with purified protein derivative (PPD) or early secretory antigenic target-6 (ESAT-6) and T-cell expressions of CCR5 and CXCR3 were assessed by flow cytometry. IFN-γ and CXCL10 were assayed by enzyme-linked immunosorbent assay., Results: TB-IRIS patients had higher proportions of PPD- and ESAT-6-reactive IFN-γ⁺CD4⁺ and CD3⁺CD4⁻ T cells at weeks 0, 2, and 6. IFN-γ levels were also higher in peripheral blood mononuclear cell culture supernatants at all times with PPD but only at weeks 2 and 6 with ESAT-6. There were few differences for interleukin-2. CXCL10 levels in supernatants after PPD and ESAT-6 stimulation were only higher at week 6. CXCR3⁺/CCR5⁺CD4⁺ T cells were higher at week 2, and CCR5⁺CD4⁺ T cells were higher at week 6., Conclusions: TB-IRIS is associated with Th1 responses against M. tuberculosis antigens by CD4⁺ and CD3⁺CD4⁻ T cells that are present before ART and amplified afterward. It is unclear if these cause immunopathology or reflect a high pathogen load.

Eleven protease mutations have been associated with reduced susceptibility to darunavir. In this study of 87 HIV-1-infected patients experiencing virological failure to second-line regimens containing protease inhibitors boosted with ritonavir (viral load >1,000 HIV RNA copies/ml), we observed a low prevalence (3%) of ≥3 darunavir resistance-associated mutations, indicating that this drug may be a good option for third-line antiretroviral therapy in southern India.

We report a high frequency of drug resistance mutations among patients with unusual insertions or deletions at the β(3)-β(4) hairpin-loop-coding region of HIV-1 subtype C reverse transcriptase, during failure of first-line antiretroviral therapy containing only reverse transcriptase inhibitors in Chennai, India.

Background: A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs)., Methods: PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8., Results: Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (interquartile range, 169-1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/mL: 33 patients (73%) had 1 of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance to lopinavir, 58% showed resistance to atazanavir, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir., Conclusions: The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that darunavir might be the drug of choice for third-line regimens in India.

Background: Little is known about patients' health literacy regarding antiretroviral therapy (ART) adherence and drug resistance and patient-provider communication about these topics., Design and Methods: The AIDS Treatment for Life International Survey was a multicountry cross-sectional study (January-March 2010) including 2035 HIV-infected adults. A 40-minute interview was conducted using a standardized self-report adherence questionnaire., Results: Overall, 57% of patients reported a 30-day recall of 100% adherence (Latin America: 89%; Africa: 73% vs North America: 45% and Asia Pacific: 47%; P < .01). Overall, 18% identified HIV drug resistance as a "good thing" in North America (35%) and Africa (24%). Only 71% said their health care providers had offered practical recommendations about adherence, 62% of the patients in North America and 80% in Latin America and Africa., Conclusions: Optimal ART adherence remains a challenge globally. There is a critical need to improve patient-provider communication about the importance of ART adherence and its benefits for patient's health.

Context: In the era of free HAART, accessibility and availability of ARV has been dramatically increased in India. However, rates of treatment literacy and adherence appear to be sub-optimal. Therefore, it is essential to monitor the extent of primary drug resistance in such settings., Materials and Methods: Between July and October 2006, 18 anti-retroviral-naοve individuals were identified as recent infected by the BED-Capture enzyme immunoassay in a VCTC clinic in Chennai. Specimens from these individuals were subjected to genotypic drug resistance testing. Phylogenetic trees were generated using MEGA for Windows version 4.0 using neighbor-joining method. The significant differences in polymorphic mutation frequencies between the study specimens and established subtype C-specific polymorphisms were examined using the Chi-square test., Results: Amino acid substitution (K103N and V106MV) at drug resistance positions occurred in two (11%) isolates, conferring high-level resistance to the non-nucleoside reverse-transcriptase inhibitors nevirapine (NVP), efavirenz (EFV), delavirdine (DLV) and notably extensive genetic variations were observed. K122E (94.4%) and K49R/KR (11.1%) polymorphisms identified in this study have not been previously described in established subtype-C specific polymorphisms. The rate of polymorphisms showed marked difference at the locations V60, D121, V35, and D123 (P < 0.0001). All the sequences showed maximum homology with Indian HIV-1 subtype C reference strain C.IN.95IN21068., Conclusions: The finding of resistance to NNRTIs is of public health importance. There is an urgent need to establish surveillance for primary drug resistance in large scale. Further studies are required to determine the phenotype impact of newer polymorphic mutations in relation to drug resistance and viral fitness.

In resource-constrained settings, the most frequently cited barrier to optimal antiretroviral therapy (ART) adherence among HIV-infected patients has been the cost of medications. In recent years many subsidized medication programs have been developed to improve ART affordability. A Graduated Cost Recovery program at the largest care center in South India has enrolled 839 eligible patients into four tiers based on an evaluation of their financial information and willingness to pay, of these patients 635 consented to participate in this study. Patients in Tier 1 receive first-line ART at no cost, whereas patients in Tiers 2, 3, and 4 pay 50, 75, and 100%, respectively of the cost of first-line medications based on an assessment of their means. Adherence rates of 95% or greater on 3-day recall were achieved by 84.6% of Tier 1 (n = 156), 71.6% of Tier 2 (n = 141), 72.3% of Tier 3 (n = 242), and 79.2% of Tier 4 (n = 96). These findings suggest patients are highly motivated and that the provision of no-cost ART can promote higher rates of optimal adherence.

Objective: To describe the safe substitution with zidovudine (AZT) among South Indian HIV-infected patients who were initiated with stavudine (d4T)-containing highly active antiretroviral therapy (HAART) due to anemia., Methods: Therapy-naïve patients initiating HAART between January 2006 and December 2007 and who had had d4T substituted for AZT at a tertiary HIV referral center in India were analyzed., Results: Six hundred and nineteen patients initiated d4T-containing HAART (median CD4 110 cells/microl; median hemoglobin 10.4 g/dl) during the study period. Subsequently half of these patients substituted d4T for AZT (median CD4 350 cells/microl; median hemoglobin 12.8 g/dl). After substituting with AZT, three patients (2.7%) who substituted after less than 6 months and one patient (0.6%) who substituted at between 6 and 12 months developed anemia. Patients who substituted after less than 6 months had significantly higher median CD4 cell counts at 1-month and 6-months of follow-up than patients who substituted at between 6 and 12 months (p<0.05). Few patients (1.6%) experienced treatment failure; about a tenth of patients developed d4T-related toxicities., Conclusion: Few patients developed anemia (1.4%) within 6 months of substitution with AZT. In settings where tenofovir is either expensive or not available and where patients are anemic, initiating d4T followed by prompt substitution with AZT can be a safe and tolerable treatment option.

Background and Objective: India has 1.1 million injecting drug users (IDUs) with an HIV prevalence rate as high as 64%. Drug resistance screening before therapy is beneficial to the individual. Here, we have studied primary drug resistance among IDUs in Chennai., Methods: Specimens (n = 55) collected between March 2005 and April 2006 were subjected to genotyping assay. The mutations for the drug resistance were interpreted using the Stanford HIV Drug Resistance Database., Results: M41LM (1.8%), K65KN (1.8%), and G73GS (2.7%) were found to be associated with low-level resistance to zidovudine (ZDV), stavudine (d4T), abacavir (ABC), didanosine (ddI), emtricitabine (FTC), tenofovir (TDF), and saquinavir (SQV) in each specimen. The rate of polymorphisms is significantly different from universally established subtype ''C''-specific polymorphisms (P < .0001)., Conclusion: The presence of drug resistance mutations, though minimal, is alarming as it could spread easily between IDUs and from them to their sexual partners. The genetic variation is of importance in vaccine design.

Continuation of failed highly active antiretroviral therapy regimens can lead to the accumulation of mutations that may limit options for second-line treatment. We studied the pattern of drug resistance mutations among 138 Indian patients who experienced failure of nonnucleotide reverse-transcriptase-containing first-line highly active antiretroviral therapy. This study demonstrates a high frequency of drug resistance mutations in human immunodeficiency virus-infected Indians who experience immunologic treatment failure and suggests the need for viral load monitoring.

Objective: The role of oxidative stress in disease progression has been shown to be more complicated in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) compared to those who remain treatment-naïve. This study examined the changes in the antioxidant profile of HIV-infected subjects who remained HAART-naïve due to a high CD4 cell count and HIV-negative controls, over a 12-month follow-up period at YRG CARE, a tertiary HIV referral centre in southern India., Methods: We prospectively studied 35 HIV-infected participants (18 on d4T+3TC+EFV (stavudine+lamivudine+efavirenz), eight on AZT+3TC+EFV (zidovudine+lamivudine+efavirenz), and nine who were antiretroviral therapy-naïve) and 20 HIV-negative controls. Antioxidant profile (total antioxidant status, glutathione reductase, glutathione peroxidase, uric acid, ceruloplasmin, zinc, and albumin), CD4 cell count, plasma viral load, dietary intake, and history of smoking and alcohol use were determined at baseline and at twelve months., Results: At 12 months, participants on HAART showed a significant increase in glutathione peroxidase (baseline: 1765 vs. 12 months: 2850U/l; p<0.001) and albumin (3.6 vs. 4.4g/dl; p<0.001), and a significant decrease in glutathione reductase (52.6 vs. 50.5U/l; p=0.054) and uric acid (5.4 vs. 4.8mg/dl; p=0.027) compared to baseline. Also HAART-naïve participants had a significant increase in albumin (baseline: 3.7 vs.12 months: 4.3g/dl; p=0.023) and a significant decrease in zinc levels (baseline: 79.0 vs.12 months: 74.5microg/dl; p=0.052) from baseline to 12 months. HIV-negative subjects had a significant increase in glutathione reductase at 12 months from baseline (baseline: 37 vs.12 months: 39U/l; p=0.002). No significant difference in total antioxidant status, ceruloplasmin, and zinc levels were observed in HAART-experienced subjects and negative controls over the 12-month follow-up period., Conclusion: This study documents changes in antioxidants over a period of time in HAART-experienced subjects in a southern India setting.

Background: Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed., Methods: We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site., Results: A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08)., Conclusions: Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.), (2008 Massachusetts Medical Society)

Objective: To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India., Methods: Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database., Results: All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/microL. The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%)., Conclusion: The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.

The number of individuals seeking treatment for infection with human immunodeficiency virus increased as the cost of highly active antiretroviral therapy (HAART) decreased 20-fold after the introduction of generic HAART in India in the year 2000. The incidence of tuberculosis and opportunistic infections decreased to <2 cases per 100 person-years. Death rates decreased from 25 to 5 deaths per 100 person-years between 1997 and 2003.

Antiretroviral therapy (ART) for HIV is increasingly being introduced and utilized in diverse areas of the world. However, little research exists on adherence to ART in different cultural settings, particularly in developing countries such as India. This formative qualitative study examined barriers and facilitators of ART adherence among 60 (49 men, 11 women; 33 taking ART, 27 not currently taking ART) patients receiving HIV primary care at YRG CARE, a nongovernmental organization, in Chennai, India. The average participant reported becoming HIV infected through heterosexual transmission, was between 31 and 40 years old, had over ninth class standard education, was married, and generally had access to medical care; however, we obtained some qualitative data from various other risk categories. Trained ethnographers at the study site conducted in-depth interviews in the local language. These interviews were analyzed for content and ethnographic data. Almost all of the participants discussed the cost of ART as a barrier, with many reporting extended drug holidays, turning to family and/or friends, or taking drastic measures (i.e., selling family jewels, property) for financial assistance. Other barriers centered on privacy and stigma issues, such as disclosure of HIV inhibiting pill-taking and social support. Frequently discussed facilitators of adherence included perceived benefits of ART and proper adherence, perceptions about the consequences of nonadherence, and social support, if available. These data highlight the importance of reducing the cost of antiretroviral medications, involving family members in HIV care, and addressing privacy issues and stigma in counseling interventions in this setting.

We prospectively studied the initial results of 6 months of generic efavirenz-based therapy on the plasma viral load in 40 patients at YRG Centre for AIDS Research and Education, a tertiary HIV referral centre in southern India. The median baseline plasma viral load was 259,000 copies/ml and at 6 months 95% of patients had plasma viral loads less than 400 copies/ml. The data support the use of generic non-nucleoside reverse transcriptase inhibitor-based regimens in resource-limited settings.

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p

Background: HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study.Methods: In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C.Results: In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24-36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years.Conclusion: We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1. [ABSTRACT FROM AUTHOR]