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1.  Molecular Characterization of Unique Intersubtype HIV Type 1 A1/C Recombinant Strain Circulating in Pune, India 
AIDS Research and Human Retroviruses  2013;29(9):1245-1253.
Abstract
An increasing number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) all over the world has necessitated being vigilant about new recombinants. Since the first report of a recombinant virus with an A1/C mosaic in 1998 more and more B/C and A/C recombinant viruses are being reported from India. Here we report the identification and characterization of a unique HIV-1 A1/C recombinant circulating in Western India. Analysis of the full-length genome using RIP, SimPlot, and jpHMM@Gobics has confirmed its mosaic structure with insertion of subtype A1 in the backbone of subtype C at three positions: gag-pol (1973±15–2617±47), pol-vif (4879±37–5582±32), and gp41 (8437±106–8811±8); however, RIP and SimPlot showed one more small insertion in integrase (4343–4519). Phylogenetic analysis confirmed that the recombinant virus has an insertion of clade A1 in the backbone of subtype C, which has come from Indian subtype C.
doi:10.1089/aid.2013.0150
PMCID: PMC3749696  PMID: 23742670
2.  Clinical profile of HIV infected patients attending a HIV referral clinic in Pune, India 
Background & objectives:
Human immunodeficiency virus (HIV) has infected several million individuals in India. Various interventions have been implemented for early detection and prevention of transmission of HIV infection. This has progressively changed the clinical profile of HIV infected individuals and this study documents the clinical presentation of individuals positive for HIV in 2010, in Pune, Maharashtra, India.
Methods:
This cross-sectional study included subjects who had come to the HIV referral clinic for HIV testing from January to December 2010. Children as well as individuals with indeterminate HIV result were excluded from the study, and data for 1546 subjects were finally analysed.
Results:
The HIV positivity rate among all referred cases for the year 2010 was 35 per cent (male 55% and females 45%). The median age (Q1, Q3) was 31 (25.75, 39) yr. The median CD4 cell count for all HIV infected individuals (whose CD4 count was available n= 345) was 241 cells/µl and for asymptomatic HIV infected individuals was 319 cells/µl. There were 673 (43.5%) symptomatic and 873 (56.5%) asymptomatic participants. Fever, breathlessness, cough with expectoration, weight loss, loss of appetite, generalized weakness, pallor and lymphadenopathy (axillary and cervical) were found to be associated (P< 0.001) with HIV positivity. On multivariate analysis, history of Herpes zoster [AOR 11.314 (6.111-20.949)] and TB [AOR 11.214 (6.111-20.949)] was associated with HIV positivity.
Interpretation & conclusions:
Signs and symptoms associated with HIV positivity observed in this study can be used by health care providers to detect HIV infection early. Moreover, similar to HIV testing in patients with tuberculosis, strategies can be developed for considering Herpes zoster as a predictor of HIV infection.
PMCID: PMC4216502  PMID: 25297361
Clinical profile; herpes zoster; HIV; Pune, India; TB
4.  Emergence of Drug Resistance in Human Immunodeficiency Virus Type 1 Infected Patients from Pune, India, at the End of 12 Months of First Line Antiretroviral Therapy Initiation 
ISRN AIDS  2014;2014:674906.
Introduction. In India, 4,86,173 HIV infected patients are on first line antiretroviral therapy (ART) as of January 2012. HIV drug resistance (HIVDR) is drug and regimen-specific and should be balanced against the benefits of providing a given ART regimen. Material & Methods. The emergence of HIVDR mutations in a cohort of 100 consecutive HIV-1 infected individuals attending ART centre, on first line ART for 12 months, was studied. CD4+ T-cell counts and plasma HIV-1 RNA level were determined. Result. Out of the 100 HIV-1 infected individuals, 81 showed HIVDR prevention (HIV-1 RNA level < 1000/mL), while the remaining 19 had HIV-1 viral RNA level > 1000/mL. HIVDR genotyping was carried out for individuals with evidence of virologic failure (HIV-1 RNA level > 1000/mL). The most frequent NRTI-associated mutation observed was M184V, while K103N/S was the commonest mutation at NNRTI resistance position. Conclusion. Our study has revealed the emergence of HIVDR in HIV-1 infected patients at the end of 12 months of first line ART initiation. For NRTIs, the prevalence of HIVDR mutations was 9% and 10% for NNRTIs. Our findings will contribute information in evidence-based decision making with reference to first and second line ART delivery and prevention of HIVDR emergence.
doi:10.1155/2014/674906
PMCID: PMC4003797  PMID: 25006528
5.  Evaluation of a Cost Effective In-House Method for HIV-1 Drug Resistance Genotyping Using Plasma Samples 
PLoS ONE  2014;9(2):e87441.
Objectives
Validation of a cost effective in-house method for HIV-1 drug resistance genotyping using plasma samples.
Design
The validation includes the establishment of analytical performance characteristics such as accuracy, reproducibility, precision and sensitivity.
Methods
The accuracy was assessed by comparing 26 paired Virological Quality Assessment (VQA) proficiency testing panel sequences generated by in-house and ViroSeq Genotyping System 2.0 (Celera Diagnostics, US) as a gold standard. The reproducibility and precision were carried out on five samples with five replicates representing multiple HIV-1 subtypes (A, B, C) and resistance patterns. The amplification sensitivity was evaluated on HIV-1 positive plasma samples (n = 88) with known viral loads ranges from 1000–1.8 million RNA copies/ml.
Results
Comparison of the nucleotide sequences generated by ViroSeq and in-house method showed 99.41±0.46 and 99.68±0.35% mean nucleotide and amino acid identity respectively. Out of 135 Stanford HIVdb listed HIV-1 drug resistance mutations, partial discordance was observed at 15 positions and complete discordance was absent. The reproducibility and precision study showed high nucleotide sequence identities i.e. 99.88±0.10 and 99.82±0.20 respectively. The in-house method showed 100% analytical sensitivity on the samples with HIV-1 viral load >1000 RNA copies/ml. The cost of running the in-house method is only 50% of that for ViroSeq method (112$ vs 300$), thus making it cost effective.
Conclusions
The validated cost effective in-house method may be used to collect surveillance data on the emergence and transmission of HIV-1 drug resistance in resource limited countries. Moreover, the wide applications of a cost effective and validated in-house method for HIV-1 drug resistance testing will facilitate the decision making for the appropriate management of HIV infected patients.
doi:10.1371/journal.pone.0087441
PMCID: PMC3922725  PMID: 24533056
6.  Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India 
Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/μL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART.
doi:10.1093/cid/cis005
PMCID: PMC3338312  PMID: 22544202
7.  Use of first line antiretroviral therapy from a free ART programme clinic in Pune, India - A preliminary report 
Background & objectives:
The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India.
Methods:
Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients.
Results:
One hundred and forty two patients with median CD4 count of 109 cells/μl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/μl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8).
Interpretation & conclusions:
The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.
PMCID: PMC3734687  PMID: 23760381
AIDS; ART Centre; CD4 counts; HIV; viral load
8.  Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings 
PLoS Medicine  2012;9(8):e1001290.
Thomas Campbell and colleagues report findings of a randomized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing.
Background
Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.
Methods and Findings
1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.
An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007).
Conclusion
EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.
Trial Registration
www.ClinicalTrials.gov NCT00084136
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Despite the enormous gains in reducing HIV-related illness and death over the past decade, there are still considerable challenges to meeting the global goal of universal access to highly active antiretroviral treatment—a combination of effective drugs that attack the HIV virus in various ways—to everyone living with HIV/AIDS who could benefit from treatment. In recognition of the related financial, technical, and system obstacles to providing universal access to HIV treatment, in 2010 the UN agency responsible for HIV/AIDS—UNAIDS—launched an ambitious plan called Treatment 2.0, which aims to simplify the way HIV treatment is currently provided. One of the main focuses of Treatment 2.0 is to simplify drug regimes for the treatment of HIV and to make treatment regimes less toxic. In line with Treatment 2.0, the World Health Organization currently recommends that antiretroviral regimens for the initial treatment of HIV should include two nucleoside reverse transcriptase inhibitors (zidovudine or tenofovir disoproxil fumarate [DF] with lamivudine or emtricitabine) and a non-nucleoside reverse transcriptase inhibitor (efavirenz or nevirapine.)
Why Was This Study Done?
Most of the evidence about the safety and effectiveness of clinical trials come from clinical trials in high-income countries and thus is not generally representative of the majority of people with HIV. So in this study, the researchers conducted a randomized controlled trial in diverse populations in many different settings to investigate whether antiretroviral regimens administered once daily were as effective as twice-daily regimens and also whether a regimen containing the drug atazanavir administered once daily was as safe and effective as a regimen containing efavirenz—data from previous studies have suggested that atazanavir has characteristics, such as its side effect profile, which may make it more suitable for low income settings.
What Did the Researchers Do and Find?
The researchers recruited eligible patients from centers in Brazil, Haiti, India, Malawi, Peru, South Africa, Thailand, the United States, and Zimbabwe—almost half (47%) were women. Then the researchers randomly assigned participants to one of three regimens: efavirenz 600 mg daily plus co-formulated lamivudine-zidovudine 150 mg/300 mg twice daily (EFV+3TC-ZDV); or atazanavir 400 mg once daily, plus didanosine-EC 400 mg once daily, plus emtricitabine 200 mg once daily (ATV+DDI+FTC); or efavirenz 600 mg once daily plus coformulated emtricitabine-tenofovir-DF 200 mg/300 mg once daily (EFV+FTC-TDF). During the study period ATV+DDI+FTC was found to be inferior to EFV+3TC-ZDV, so the Multinational Data Safety Monitoring Board ordered this arm of the trial to stop. Then a year later, due to the low number of treatment failures (deaths, severe HIV disease, or serious opportunistic infections) in the remaining two arms, the board advised the trial to stop early. So the researchers analyzed the data obtained up to this point and pooled the results from all of the centers.
The researchers found that during an average of 184 weeks of follow-up, there were 95 treatment failures (18%) among 526 participants taking EFV+FTC-TDF compared to 98 failures among 519 participants taking EFV+3TC-ZDV. During an average 81 weeks follow-up, there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV. As for safety, 243 (46%) participants assigned to EFV+FTC-TDF reached a safety endpoint (grade 3 disease, abnormal lab measurement, or the need to change drug) compared to 313 (60%) in the EFV+3TC-ZDV group. Importantly, the researchers found that there was greater risk of safety events for women assigned to EFV+3TC-ZDV and also that the atazanavir-based regimen had a higher relative efficacy in women compared to men.
What Do These Findings Mean?
These findings suggest that in diverse populations, EFV+FTC-TDF is as effective as EFV+3TC-ZDV but importantly, the once-daily dosing of EFV+FTC-TDF makes this regimen useful for the initial treatment of HIV, especially in low-income countries. Therefore, as per the guidance in Treatment 2.0, EFV+FTC-TDF in a single combination tablet that can be taken once a day is an attractive option. These findings also indicate that as ATV+DDI+FTC was found to be inferior to the other regimens, this combination should not be used in the initial treatment of HIV. These findings also add to the evidence that antiretroviral efficacy and safety can differ between women and men and support further development of sex-specific recommendations for antiretroviral regimen options.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001290.
The UNAIDS website has more information about Treatment 2.0; and the WHO website provides technical information
For an introduction to the treatment of HIV/AIDS see http://www.avert.org/treatment.htm; the AVERT site also has personal stories from women living with HIV/AIDS
AIDSmap provides information for individuals and communities affected by HIV/AIDS
The ACTG website provides information about research to improve treatment of HIV and related complications
doi:10.1371/journal.pmed.1001290
PMCID: PMC3419182  PMID: 22936892
9.  Maternal Tuberculosis: A Risk Factor for Mother-to-Child Transmission of Human Immunodeficiency Virus 
The Journal of Infectious Diseases  2011;203(3):358-362.
Background. Maternal human immunodeficiency virus (HIV) RNA load, CD4 cell count, breast-feeding, antiretroviral use, and malaria are well-established factors associated with mother-to-child transmission (MTCT) of HIV; the role of maternal tuberculosis (TB), however, has not been well established.
Methods. The study population was 783 HIV-infected Indian mother-infant pair participants in randomized and ancillary HIV-infected cohorts of the Six Week Extended-Dose Nevirapine (SWEN) Study, a study comparing extended nevirapine versus single-dose nevirapine, to reduce MTCT of HIV among breast-fed infants. Using multivariable logistic regression, we assessed the impact of maternal TB occurring during pregnancy and through 12 months after delivery on risk of MTCT.
Results. Of 783 mothers, 3 had prevalent TB and 30 had incident TB at 12 months after delivery. Of 33 mothers with TB, 10 (30%) transmitted HIV to their infants in comparison with 87 of 750 mothers without TB (12%; odds ratio [OR], 3.31; 95% confidence interval [CI], 1.53–7.29; P = .02). In multivariable analysis, maternal TB was associated with 2.51-fold (95% CI, 1.05–6.02; P = .04) increased odds of HIV transmission adjusting for maternal factors (viral load, CD4 cell count, and antiretroviral therapy) and infant factors (breast-feeding duration, infant nevirapine administration, gestational age, and birth weight) associated with MTCT of HIV.
Conclusions. Maternal TB is associated with increased MTCT of HIV. Prevention of TB among HIV-infected mothers should be a high priority for communities with significant HIV/TB burden.
doi:10.1093/jinfdis/jiq064
PMCID: PMC3071111  PMID: 21208928
10.  High Rates of All-cause and Gastroenteritis-related Hospitalization Morbidity and Mortality among HIV-exposed Indian Infants 
BMC Infectious Diseases  2011;11:193.
Background
HIV-infected and HIV-exposed, uninfected infants experience a high burden of infectious morbidity and mortality. Hospitalization is an important metric for morbidity and is associated with high mortality, yet, little is known about rates and causes of hospitalization among these infants in the first 12 months of life.
Methods
Using data from a prevention of mother-to-child transmission (PMTCT) trial (India SWEN), where HIV-exposed breastfed infants were given extended nevirapine, we measured 12-month infant all-cause and cause-specific hospitalization rates and hospitalization risk factors.
Results
Among 737 HIV-exposed Indian infants, 93 (13%) were HIV-infected, 15 (16%) were on HAART, and 260 (35%) were hospitalized 381 times by 12 months of life. Fifty-six percent of the hospitalizations were attributed to infections; gastroenteritis was most common accounting for 31% of infectious hospitalizations. Gastrointestinal-related hospitalizations steadily increased over time, peaking around 9 months. The 12-month all-cause hospitalization, gastroenteritis-related hospitalization, and in-hospital mortality rates were 906/1000 PY, 229/1000 PY, and 35/1000 PY respectively among HIV-infected infants and 497/1000 PY, 107/1000 PY, and 3/1000 PY respectively among HIV-exposed, uninfected infants. Advanced maternal age, infant HIV infection, gestational age, and male sex were associated with higher all-cause hospitalization risk while shorter duration of breastfeeding and abrupt weaning were associated with gastroenteritis-related hospitalization.
Conclusions
HIV-exposed Indian infants experience high rates of all-cause and infectious hospitalization (particularly gastroenteritis) and in-hospital mortality. HIV-infected infants are nearly 2-fold more likely to experience hospitalization and 10-fold more likely to die compared to HIV-exposed, uninfected infants. The combination of scaling up HIV PMTCT programs and implementing proven health measures against infections could significantly reduce hospitalization morbidity and mortality among HIV-exposed Indian infants.
doi:10.1186/1471-2334-11-193
PMCID: PMC3161884  PMID: 21762502
Infant; HIV; India; Hospitalization; In-hospital Mortality; gastroenteritis; pneumonia
11.  T-cell Epitopes Identified by BALB/c Mice Immunized with Vaccinia Expressing HIV-1 Gag lie within immunodominant Regions Recognized by HIV-infected Indian Patients 
Background:
Human immunodeficiency virus (HIV) antigens from transmitted strains of HIV would prove crucial in vaccine designing for prevention of HIV infection. Immune response generated by Vaccinia construct expressing the HIV-1 gag gene from transmitted Indian HIV-1 subtype C strain (Vgag) in BALB/c mice is reported in the present study along with the identification of epitopes responsible for induction of the immune response.
Aims:
The aim of this study was to determine immune response generated by the constructs in a mouse model and to understand the epitope specificities of the response.
Settings and Design:
This was an observational study carried out in BALB/c mice.
Materials and Methods:
The immunogenecity of Vgag construct was evaluated in BALB/c mice after multiple immunizations. T-cell response was monitored by the interferon-γ ELISPOT assay using HIV-1 C Gag overlapping peptides and anti-P24 antibodies were estimated by ELISA.
Statistical Analysis Used:
Graphpad prism software was used for statistical analysis and for plotting graphs.
Results:
IFN-γ-secreting T cells and antibodies were detected against HIV Gag in mice after immunization. Although after repeated immunizations, antibody-mediated immune response increased or remained sustained, the magnitude of IFN-γ-secreting T cell was found to be decreased over time. The Gag peptides recognized by mice were mainly confined to the P24 region and had a considerable overlap with earlier reported immunodominant regions recognized by HIV-infected Indian patients.
Conclusion:
Vaccinia construct with a gag gene from transmitted HIV-1 virus was found to be immunogenic. The Gag regions identified by mice could have important implications in terms of future HIV vaccine designing.
doi:10.4103/0974-777X.83530
PMCID: PMC3162811  PMID: 21887056
Cellular immune response; T-cell epitopes; Vgag
12.  Mortality in HIV infected individuals in Pune, India 
Background & objectives:
With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India
Methods:
A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death.
Results:
Median CD4 count in study participants was 218 cells/µl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/µl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09), P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively].
Interpretation & conclusions:
High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme.
PMCID: PMC3103175  PMID: 21537095
ART; CD4 count; HIV; immunosuppression; India; mortality
13.  One-, Two-, and Three-Class Resistance among HIV-Infected Patients on Antiretroviral Therapy in Private Care Clinics: Mumbai, India 
Abstract
HIV-infected patients receiving antiretroviral (ARV) therapy (ART) in India are not all adequately virally suppressed. We analyzed ARV drug resistance in adults receiving ART in three private clinics in Mumbai, India. HIV viral load was measured in 200 patients with the Roche AMPLICOR HIV-1 Monitor Test, v1.5. HIV genotyping was performed with the ViroSeq HIV-1 Genotyping System for 61 participants who had HIV-1 RNA >1000 copies/ml. Genotyping results were obtained for 51 samples. The participants with resistance results were on ART for a median of 24 months and were on their current regimen for a median of 12 months (median CD4 cell count: 217 cells/mm3; median HIV viral load: 28,200 copies/ml). ARV regimens included nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (n = 27), dual nucleoside reverse transcriptase inhibitors (NRTIs, n = 19), protease inhibitor (PI)-based regimens (n = 3), and other regimens (n = 2). Twenty-six participants (51.0%) were on their first ARV regimen and 24 (47%) reported >95% adherence. Forty-nine participants (96.1%) had resistance to at least one ARV drug; 47 (92.2%) had NRTI resistance, 32 (62.7%) had NNRTI resistance, and four (7.8%) had PI resistance. Thirty (58.8%) had two-class resistance and three (5.9%) had three-class resistance. Four (8%) had three or more resistance mutations associated with etravirine resistance and two (4%) had two mutations associated with reduced darunavir susceptibility. Almost all patients with HIV-1 RNA >1000 copies/ml had NRTI resistance and nearly two-thirds had NNRTI resistance; PI resistance was uncommon. Nearly 60% and 6% had two- and three-class resistance, respectively. This emphasizes the need for greater viral load and resistance monitoring, use of optimal ART combinations, and increased availability of second- and third-line agents for patients with ARV resistance.
doi:10.1089/aid.2009.0102
PMCID: PMC2858895  PMID: 20063995
14.  Short Communication: Neutralizing Antibody Responses in Recent Seroconverters with HIV-1 Subtype C Infections in India 
AIDS Research and Human Retroviruses  2008;24(9):1159-1166.
Abstract
The longitudinal heterologous neutralization response against two HIV-1 subtype C isolates was studied in 33 ART-naive individuals recently infected with HIV-1 subtype C from India. Seven of 33 (21%) seroconverters demonstrated a consistent response against both isolates (65–100% neutralization), whereas the remaining 26 (79%) were nonresponders. Four of the seven responders demonstrated a neutralization response (>75% neutralization) within 2–3 months of infection and in the remaining three, the response was demonstrated between 22 and 38 months after infection. In the past, HIV vaccines targeted the V3 region for the development of neutralizing antibodies. However, recent studies have shown that anti-V3 antibodies are generated after HIV-1 infection, but are not effective in neutralizing virus. In this study, the V3 sequences of HIV-1 from seven responders were analyzed and compared with those from nonresponders. The V3 region sequences from early and late responders did show certain mutations that were not found in the nonresponders; however none of these mutations could explain the neutralization responses. This suggested that HIV-1 envelope regions other than the V3 domain may be involved in generating a neutralization response. This is the first report that describes the pattern of emergence and persistence of the heterologous neutralization response in recently HIV-1 subtype C-infected individuals from India and studies its association with sequence variation in the V3 region.
doi:10.1089/aid.2007.0296
PMCID: PMC2928029  PMID: 18665801
15.  Nevirapine Resistance and Breast-Milk HIV Transmission: Effects of Single and Extended-Dose Nevirapine Prophylaxis in Subtype C HIV-Infected Infants 
PLoS ONE  2009;4(1):e4096.
Background
Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the “six-week extended-dose nevirapine” (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.
Methods/Findings
Standard population sequencing and cloning for viral subpopulations present at ≥5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.
Conclusions/Significance
Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.
Trial Registration
ClinicalTrials.gov NCT00061321
doi:10.1371/journal.pone.0004096
PMCID: PMC2606064  PMID: 19119321

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