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We assessed the impact of pre-exposure prophylaxis (PrEP) in the context of a community-based HIV program among female sex workers (FSWs) in Kolkata, India. This was an open-label, uncontrolled demonstration trial. HIV seronegative FSWs over 18 years were eligible. Participants were administered daily tenofovir/emtricitabine (TDF-FTC) with follow-up visits at months 1, 3, 6, 9, 12, and 15. Drug adherence was monitored by self-report, and a random subset of participants underwent plasma TDF testing. 843 women were screened and 678 enrolled and started on PrEP. Seventy-nine women (11%) did not complete all scheduled visits: four women died of reasons unrelated to PrEP and 75 withdrew, for a 15-month retention rate of 89%. Self-reported daily adherence was over 70%. Among those tested for TDF, the percentage of women whose level reached ≥40 ng/mL was 65% by their final visit. There were no HIV seroconversions, and no evidence of significant changes in sexual behavior. This study demonstrated the feasibility and effectiveness of PrEP for FSWs in Kolkata, with very high levels of adherence to PrEP and no HIV seroconversions. The integration of PrEP into an existing community-based HIV prevention program ensured community support and facilitated adherence.

We evaluated the prevalence and determinants of bacterial vaginosis (BV) in HIV-infected women from Maharashtra, India. Among 912 HIV-infected women enrolled, BV was diagnosed in 191 (20.9%) and intermediate BV was diagnosed in 258 (28.3%) women. Women with more than two pregnancies had 1.6 times increased risk of BV (95% CI 1.0, 2.5, p-value 0.038), women who were menopausal had 6.2 times increased risk of BV (95% CI 2.4, 15.6, p-value

Transgenders (TGs) are highly affected by HIV with high prevalence of 3.14% in India. Since 2017, targeted preventive efforts have been initiated by the government and HIV-infected TGs are being provided the antiretroviral (ART) treatment. Information on the primary HIV drug resistance is crucial for appropriate treatment selection to curb further spread of HIV in this population. In this study, we analyzed HIV-1 pol gene sequences from 36 TGs for presence of drug resistance mutations. To our knowledge, this first study from India reports high-level primary drug resistance (13.8%) among the TG population. Mutations M184V, A98G, K103N, G190A, and Y318F associated with resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitors were observed. All pol gene sequences revealed HIV-1 subtype C in all study TG. High-level HIV-1 drug resistance warrant nationwide larger studies on TGs to understand the level of primary ART drug resistance among this population.

Background:IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production.Methods:Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method.Results:In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16).Conclusion:Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

Background: Immunological non-responders (INR) represent a unique category of HIV-infected patients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections. Methods: Twenty-three INR patients (CD4 increase 100 cells/mm3, viral load

Background: High-quality data are of prime importance in any health survey because survey data are considered as a gold standard for nationally representative data. The quality of data collection largely depends on the design of the questionnaire, training, and skills of the interviewer. Objectives: In the present study, we tried to evaluate three key components, such as questionnaire design, human resource and training of the field staff for Integrated Biological and Behavioural Surveillance carried out among the HIV high-risk subpopulation. Methods: A mixed-methods approach was used. Qualitative and quantitative data collection was carried out in the year 2015 with cross-sectional survey design in western states of India. The in-depth interviews of 10 stakeholders, structured interviews of the survey respondents (n = 560), and field investigators (n = 71) were conducted. Data triangulation was used to find out the concurrence of the qualitative and quantitative data. Results: Comprehensive and standardized survey questionnaire, structured training agenda, and strategic preparation for recruiting human resources were the overall strengths of the survey. However, during the implementation of the survey, there were some difficulties reported in data collection process. Overall, the respondents and investigators felt that the questionnaire was long and exhaustive. Difficulties were faced while collecting data on sexual history. The field staffs were not adequately experienced to work with sensitive population. Conclusions: In order to have accurate, reliable data, especially on sexual behavior; emphasis should be given on simple questionnaire with the use of community-friendly language, skilled and experienced interviewers for data collection, and extensive field training.

Hepatic CYP2D6 enzyme metabolizes antiretroviral drugs (ARVs) including nevirapine. Polymorphism in CYP2D6 gene affects drug metabolism and displays distinctive phenotypes in the population. Hence, we investigated the prevalence of CYP2D6*4 1934G/A polymorphism in a total of 165 HIV patients that include 34 with and 131 without hepatotoxicity and 160 unrelated healthy controls by the PCR-RFLP method. The prevalence of CYP2D6*4 1934AA genotype was higher in total HIV patients as compared to healthy controls (1.81% vs 0.6%, OR = 2.86). Similarly, CYP2D6*4 1934AA genotype was much more prevalent in HIV patients without hepatotoxicity as compared to healthy controls (2.3% vs 0.6%, OR = 2.87). Likewise, CYP2D6*4 1934AA genotype was predominant in advanced HIV disease stage as compared to healthy controls (3.8% vs 0.6%, OR = 6.15). CYP2D6*4 1934GA genotype was distributed higher in HIV patients taking tobacco and nevirapine as compared to non-users (23.3% vs 19.3%, OR = 1.21, 21.0% vs 16.7%, OR = 1.2). Likewise, CYP2D6*4 1934GA genotype was overrepresented in patients with hepatotoxicity taking alcohol + nevirapine as compared to alcohol non-users + nevirapine users (20.00% vs 16.67%, OR = 1.25). Thus, there was no significant difference in genotype or allele frequencies of CYP2D6*4 1934G/A polymorphism between the patients with hepatotoxicity and those without or healthy controls.

The genetic variations in APOBEC3G gene are correlated with HIV disease progression. These variations differ in different ethnic groups. The prevalence of APOBEC3G (-90C/G, −571G/C) variations have not been studied in Indian population. Hence, we assessed the occurrence of APOBEC3G polymorphisms in HIV patients and its association with acquisition of HIV and disease progression. Polymorphisms in APOBEC3G were genotyped in a total of 153 HIV patients, naive to ARV and 156 healthy controls by PCR-RFLP method. In single locus model, the frequency of distribution of APOBEC3G −90CG, −571 GC genotypes were higher in HIV patients as compared to healthy controls (57.5% vs. 50.0%, OR = 1.22; 17.0% vs. 12.8%, OR = 1.39). In double locus model, the dominant −571 GC + CC genotype was distributed at a much higher frequency in HIV patients as compared to healthy controls (18.3% vs. 14.1%, OR = 1.50). The frequency of APOBEC3G −571CC and CC + GC genotypes were higher in early HIV disease stage as compared to healthy controls (23.9% vs. 12.8%, OR = 2.23, P = 0.08; 28.3% vs. 14.1%, OR = 2.40, P = 0.04). APOBEC3G-571 GC and GC + CC genotypes were more prevalent in HIV patients consuming tobacco and alcohol as compared to non-users (22.7% vs. 15.3%, OR = 1.71, P = 0.56; 27.3% vs. 16.5%, OR = 1.90, P = 0.39 and 31.6% vs. 13.6%, OR = 2.31, P = 0.08; 36.8% vs14.8%, OR = 2.49, P = 0.04, respectively). In conclusion, APOBEC3G-571G/C polymorphism was associated with the early stage of HIV infection and could potentially influence HIV disease progression in alcohol users. The distribution of APOBEC3G polymorphisms and its haplotypes were not significantly different between HIV patients and healthy controls.

Matrix metalloproteinases (MMPs) are well-known as mediators of neuroinflammation in HIV-associated neurocognitive disorder (HAND). Increased levels of MMP-8 have been observed in the HIV-infected patients. Thus, the aim of this study was to evaluate the association of MMP-8 gene polymorphisms with modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. We enrolled a total of 150 HIV-infected individuals, 50 HAND patients, 100 HIV-infected and 150 healthy individuals. MMP-8 (-799C/T, + 17C/G) polymorphisms were genotyped by PCR-RFLP. MMP-8 − 799TT genotype and + 17G allele showed the higher risk for modulation of HAND severity (OR = 2.20, P = 0.19; OR = 1.97, P = 0.23). MMP-8 − 799TT genotype differed significantly in HIV-infected individuals compared to healthy controls (20.0% vs. 11.3%, OR = 2.36, P = 0.048). Haplotype TG increased the risk for modulation of HAND severity (OR = 2.29, P = 0.29). MMP-8 − 799TT and + 17CG genotypes were overrepresented in the intermediate HIV disease stage compared with healthy controls (25.9% vs. 11.3%, OR = 4.34, P = 0.021, 14.8% vs. 9.3%, OR = 2.88, P = 0.11). MMP-8 + 17CG genotype enhanced the risk for modulation of HAND severity in tobacco using HAND patients (OR = 5.01, P = 0.17). MMP-8 − 799TT genotype was more frequent in tobacco using HIV-infected individuals compared with nonusers (26.3% vs. 16.7%, OR = 2.08, P = 0.32). MMP-8 + 17CG genotype increased the risk for modulation of HAND severity in alcohol using HAND patients (OR = 4.99, P = 0.18). In conclusion, MMP-8 polymorphisms independently and with alcohol and tobacco usage revealed a trend of higher risk for the modulation of HAND severity. MMP-8 − 799TT genotype was associated with the advancement of HIV disease.

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.

BackgroundThe first case of HIV infection in Sri Lanka was reported in 1987 and at the end of 2018 there were 3500 people living with HIV. There have been commendable efforts made towards the detection, treatment, and prevention of HIV in the country. Even though the genetic diversity of HIV has been shown to affect the parameters ranging from detection to vaccine development, there is no data available with respect to the molecular epidemiology of HIV-1 in Sri Lanka.MethodsIn this report we have performed the ancillary analysis of pol gene region sequences (n = 85) obtained primarily for the purpose of HIV-1 drug resistance genotyping. Briefly, dried blood spot specimens (DBS) collected from HIV-1 infected individuals between December 2015 and August 2018 were subjected to pol gene amplification and sequencing. These pol gene sequences were used to interpret the drug resistance mutation profiles. Further, sequences were subjected to HIV-1 subtyping using REGA 3.0, COMET, jPHMM and, RIP online subtyping tools. Moreover, Bayesian phylogenetic analysis was employed to estimate the evolutionary history of HIV-1 subtype C in Sri Lanka.ResultsOur analysis revealed that the majority (51.8%) of pol gene sequences were subtype C. Other than subtype C, there were sequences categorized as subtypes A1, B, D and G. In addition to pure subtypes there were sequences which were observed to be circulating recombinant forms (CRFs) and a few of the recombinants were identified as potential unique recombinants (URFs). We also observed the presence of drug resistance mutations in 56 (65.9%) out of 85 sequences. Estimates of the Bayesian evolutionary analysis suggested that the HIV-1 subtype C was introduced to Sri Lanka during the early 1970s (1972.8).ConclusionThe findings presented here indicate the presence of multiple HIV-1 subtypes and the prevalence of drug resistance mutations in Sri Lanka. The majority of the sequences were subtype C, having their most recent common ancestor traced back to the early 1970s. Continuous molecular surveillance of HIV-1 molecular epidemiology will be crucial to keep track of drug resistance, genetic diversity, and evolutionary history of HIV-1 in Sri Lanka.

The flat-lining of HIV incidence in India has raised concerns about the presence of emerging risk groups. As HIV prevalence among pregnant women is reflective of the situation in general population, its closer scrutiny provides valuable insights about the evolving epidemic. The present study assesses temporal trends of sero-discordance (where woman is HIV infected and husband is uninfected), among pregnant women living with HIV (pWLHIV) from India. Data of program for prevention of parent to child transmission of HIV was analyzed. Statistical analysis was done using Cochrane-Armitage trend test and logistic regression. Of the 1209 currently married pWLHIV, 302 (25%) were sero-discordant. The proportion increased from 16% in 2007 to 36% in 2016-17 (p = 0.000). The likelihood of sero-discordance was higher for women aged 18-20 (OR: 2.68, CI: 1.30-5.83) and 21-23 (OR: 1.98, CI: 1.01-4.15) years compared to 36-40 years; and for primi-parous women (OR: 1.84, CI: 1.31-2.58) compared to women pregnant for second/third time. The findings are indicative of changing HIV transmission dynamics. Steeper rise in sero-discordance in younger women implies an increasing risk of HIV in unmarried women population. A better understanding of HIV specific vulnerabilities of young women, married and unmarried, is warranted.

SETTING Little is known about outcomes of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) who are treated in the private sector in India. OBJECTIVE To describe the treatment outcomes of daily anti-tuberculosis treatment (ATT) and their determinants among HIV-TB co-infected patients treated at a private clinic in Pune, India. DESIGN Data on adult HIV-TB co-infected patients treated with daily ATT were analysed using logistic regression and Cox model to assess risk factors for default and death. RESULTS Of 769 cases, 78% were aged 2 months) and 3.9% died during ATT. The risk of default was higher among males (aOR 1.67, 95%CI 1.17-2.39), ART-naive patients (aOR 1.91, 95%CI 1.34-2.73) and those with a past history of TB (aOR 1.86, 95%CI 1.15-3.01). Survival probability at 365 days was 95% (95%CI 93-97). The risk of death was higher among patients with CD4 200 cells/mm3. CONCLUSIONS Low overall mortality was seen with daily ATT in HIV-TB co-infected patients. High default rates in private facilities warrant urgent attention.

In India, the roll out of the free antiretroviral therapy (ART) program completed a decade of its initiation in 2014. The success of first-line ART is influenced by prevalence of HIV pretreatment drug resistance (PDR) in the population. In this cross-sectional study, we sought to determine the prevalence of PDR among adults attending the state-sponsored free ART clinic in Pune in western India. Fifty-two individuals eligible for ART as per national guidelines with median CD4 cell count of 253 cells/mm(3) (inter quartile range: 149-326) were recruited between January 2014 and April 2015. Population-based sequencing of partial pol gene sequences from plasma specimen revealed predominant HIV-1 subtype C infection (96.15%) and presence of single-drug resistance mutations against non-nucleoside reverse transcriptase inhibitor in two sequences. The study supports the need for periodic surveillance, when offering PDR testing at individual level is not feasible.

The allelic variations in the AIDS restriction genes have been associated with the acquisition of HIV-1 and its progression. The distribution of antiviral gene variants significantly differs between populations. Therefore, we aimed to evaluate the distribution of variant allele of 186H/R in exon4 of APOBEC3G between HIV infected individuals and healthy controls among western Indian.In the present cross-sectional study, we enrolled a total of 153 HIV-infected patients confirmed and 156 unrelated healthy individuals. Polymorphism for 186H/R in exon4 of APOBEC3G gene was genotyped by PCR-RFLP. With the frequency of 186HR heterozygous genotype of APOBEC3G was found to be 13% in healthy controls and none in HIV infected cases. The frequency of 186HH common genotype of APOBEC3G was observed higher in HIV infected individuals compared with healthy controls (100% vs 91.7%). The variant genotype 186RR in APOBEC3G was not found in both the groups. The frequency of 186R allele of APOBEC3G was found 4.16% in healthy controls and nil in HIV-infected cases. The frequency of 186H allele of APOBEC3G was found to be higher in HIV-infected cases compared with healthy controls (100% vs 95.83%). The frequency of 186R allele in exon4 of APOBEC3G was found to be 4.16% in healthy controls. This observation differs from the previous report published from North India stating the absence of 186R allele of APOBEC3G in the North Indian individuals. The variant 186H/R in exon4 of APOBEC3G was neither associated with risk of acquisition of HIV-1 nor its progression.

HIV-2 is important due to its unique challenges in diagnosis, treatment, and drug resistance. The data on Indian HIV-2

BACKGROUND Although HIV incidence has declined in India, men and transgender women who have sex with men (MSM) continue to have high rates of HIV and sexually transmitted disease (STD). Indian MSM face substantial pressures to marry and have families, but the HIV/STD burden among married Indian MSM is not well characterized. METHODS A diverse sample of Indian MSM were recruited through respondent-driven sampling. Independent variables that produced a P value of 0.10 or less were then added to a multivariable logistic regression model. RESULTS Most of the 307 MSM (95 married and 212 unmarried) recruited into the study were younger than 30 years, and less than one-third had more than a high school education. Almost two-thirds of the married men had children, compared with 1.4% of the unmarried men (P < 0.001). The numbers of condomless anal sex acts did not differ by marriage status. Although unmarried MSM more often identified themselves as "kothi" (receptive role), their rates of HIV or bacterial STD were similar to married MSM, with 14.3% being HIV infected. The respondent-driven sampling-adjusted prevalence of any bacterial STD was 18.3% for married MSM and 20% for unmarried MSM (not significant). Participants reported high levels of psychological distress, with 27.4% of married and 20.1% of unmarried MSM reporting depressive symptoms (not significant). CONCLUSIONS Men who have sex with men in Mumbai had high rates of HIV, STD, and behavioral health concerns. Clinicians need to become more comfortable in eliciting sexual histories so that they can identify MSM who need HIV/STD treatment and/or prevention services.

Introduction The HIV sentinel surveillance [HSS] conducted in 2010–11 among female sex workers [FSW] in the state of Maharashtra, India provided an opportunity to assess characteristics of different types of FSWs and their HIV risk. It is important for India’s National AIDS Control Program, to understand the differences in vulnerability among these FSW, in order to define more specific and effective risk reduction intervention strategies. Therefore, we analyzed data from HSS with the objective of understanding the HIV vulnerability among different types of FSW in Maharashtra. Material and methods Cross sectional data collected as a part of HSS among FSWs in year 2010–11 from 21 sentinel sites in the state of Maharashtra were analyzed to understand the vulnerability and characteristics of different types of female sex workers based on their place of solicitation using multinomial logistic regression. Results While the HIV prevalence was 6.6% among all FSWs, it was 9.9% among brothel based [BB], 9% among street based [SB] and 3.1% and 3.7% among home based [HB], and bar based [Bar-B] sex workers respectively. SB FSWs were least likely to be located in HIV low burden districts [ANC] [ARRR: 0.61[95% CI: 0.49, 0.77]], but were 6 times more likely to be recently [1%). We identify them as a group to be focused on for prevention interventions and it is likely that they would be easily amenable to novel interventions due to their higher literacy rate as compared to other typologies.

Objective The objective of this review was to assess the burden of HIV drug resistance mutations (DRM) in Indian adults exposed to first-line antiretroviral therapy (ART) as per national guidelines. Methods An advanced search of the published literature on HIV drug resistance in India was performed in the PubMed and Scopus databases. Data pertaining to age, sex, CD4 count, viral load, and prevalence of nucleoside reverse transcriptase inhibitor (NRTI)/non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM were extracted from each publication. Year-wise Indian HIV-1 reverse transcriptase (RT) sequences were retrieved from the Los Alamos HIV database and mutation analyses were performed. A time trend analysis of the proportion of sequences showing NRTI resistance mutations among individuals exposed to first-line ART was conducted. Results Overall, 23 studies (1046 unique RT sequences) were identified indicating a prevalence of drug resistance to NRTI and NNRTI. The proportion of RT sequences with any DRM, any NRTI DRM, and any NNRTI DRM was 78.39%, 68.83%, and 73.13%, respectively. The temporal trend analysis of individual DRM from sequences retrieved during 2004–2014 indicated a rising trend in K65R mutations ( p =0.013). Conclusions Although the overall burden of resistance against first-line ART agents remained steady over the study decade, periodic monitoring is essential. There is the need to develop an HIV-1 subtype C-specific resistance database in India.

Background Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. Methods A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. Results The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p

Background TRIM5α and BST-2 are cellular restriction factors affecting the HIV-1 infection and its progression. Genetic variability in these genes alters the expression pattern. Hence, we aimed to examine the impact of the TRIM5α (rs10838525, rs7127617 and rs904375) and BST2 (rs3217318 and rs71694748) polymorphisms on the acquisition of HIV-1 and its progression. Methods Genotyping of TRIM5α and BST-2 polymorphisms was performed in a total of 153 HIV-infected patients and 158 unrelated healthy individuals using a polymerase chain reaction-restriction fragment length polymorphism method. Results No significant differences were found in the genotype frequencies of TRIM5α polymorphisms between HIV patients and healthy controls. BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes appeared more frequently in HIV patients compared to healthy controls (10.4% versus 7.0%, p = 0.20; 11.10% versus 7.6%, p = 0.16). The BST-2 i19 allele was associated with the acquisition of HIV-1 [odds ratio (OR) = 2.76, p = 0.030)]. TRIM5α haplotypes ATG and ACA elevated the risk, whereas haplotype ATA reduced the risk for the acquisition of HIV-1 (OR = 1.92, p = 0.026; OR = 4.88, p = 0.016; OR = 0.31, p = 0.014). BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes were more prevalent in patients with early HIV disease stage compared to healthy controls (15.9% versus 7.0%, p = 0.096; 15.9% versus 7.6%, p = 0.12). The prevalence of TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes was observed to be higher in alcohol-using HIV patients compared to non-users (27.8% versus 20.0%, p = 0.35, 22.2% versus 10.0%, p = 0.24). Conclusions TRIM5α haplotypes and the BST-2 i19 allele may significantly affect the modulation of HIV-1 acquisition and its progression. TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes in alcohol-using HIV patients elevated the risk of HIV disease progression.

Background The free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p

Persistent immune activation in human immunodeficiency virus (HIV) infection is responsible for alterations in immune system such as activation, apoptosis, and reduced frequencies. Reduced immune activation is known to be associated with virus control. Limited information is available on the influence of pan-immune activation on memory responses. Hence, we compared the T cell activation and memory profile in HIV-infected individuals exhibiting disease control such as long-term nonprogressors (LTNPs) and progressors. The activated CD4+ and CD8+ T cells were significantly lower and the CD4+ and CD8+ central memory T cell phenotypes were significantly higher in the LTNPs compared to the progressors. In addition, we observed significant inverse association between the T cell activation and frequencies of central memory T cells. Our findings indicate that patients with absence of disease progression have preserved central memory T cell population associated with lesser immune activation.

APOBEC3B deletion polymorphism has been associated with risk of HIV-1 acquisition and its progression. Therefore, we aimed to investigate the association of APOBEC3B ins/del polymorphism with risk of acquisition of HIV-1 and its progression. In the present case-control study, we enrolled a total of 150 HIV-infected individuals and 150 healthy controls. Polymorphism for APOBEC3B gene was genotyped by PCR. APOBEC3B ID, DD genotypes, and D allele were associated with higher risk of acquisition of HIV-1 (p = 0.004, OR = 4.96; p = 0.03, OR = 3.55; and p = 0.004; OR = 1.60). The individuals with ID genotypes and combined genotype ID+DD of APOBEC3B in the presence of tobacco and alcohol showed the higher risk of advancement of HIV disease; however, risk could not reach statistical significance (OR = 1.14, 95% CI: 0.59-2.18; OR = 1.33, 95% CI: 0.83-2.15 and OR = 1.44, 95% CI: 0.77-2.69; OR = 1.50, 95% CI: 0.94-2.40). Individuals in advanced HIV disease stage and ID genotype and combined genotype ID + DD of APOBEC3B were more likely to be associated with advanced HIV disease stage but risk could not reach significant (OR = 1.50, 95% CI: 0.94-2.40; OR = 1.27, 95% CI: 0.88-1.84). Individuals with ID and DD genotype of APOBEC3B had influence on susceptibility to acquisition of HIV-1. This suggests that APOBEC3B deletion may attenuate innate cellular immunity against HIV-1 and thus confer the host persistence for HIV infection.

The objectives of this cross-sectional study were to determine the prevalence of HIV and sexually transmitted infections (STI) in Hijras (self-identified transgenders of South Asia), study associated risk factors, and compare the prevalence with that in heterosexual men and men having sex with men (MSM) in Pune, India, between 1993 and 2002.After informed consent, individuals attending 3 STI clinics were administered a questionnaire regarding their demographic, socioeconomic, and sexual behaviors. Blood samples were collected for STI and HIV diagnosis. Bivariate and multivariate analyses were performed to determine the correlates of HIV infection.The prevalence of HIV (45.2% in Hijras vs 20% in heterosexual men vs 18.9% in MSM, P0.0001) and warts (10.3% vs 4.6% vs 7.0%; P = 0.004) was higher in Hijras as compared with heterosexual men and MSM; whereas that of genital ulcer disease (15.3% vs 32.6% vs 21.5%; P0.0001) and discharge (5.4% vs 13.6% vs 9.0%; P0.0001) was lower. Hijras were more likely to have received money for sex and have an earlier sexual debut than the comparison groups. In multivariate analysis, receiving money for sex (adjusted odds ratio: 4.49; P0.04) and having genital ulcer disease (odds ratio: 3.87; P0.08) were independently associated with high HIV prevalence in Hijras.Considering the high HIV and STI burden, it is important to review current prevention strategies and stress the need to engage Hijra community members through appropriate targeted intervention programs.

Despite an estimated 70,000 Indian children living with HIV infection, little is known about India's pediatric HIV epidemic. Generalizations about epidemiology, natural history, and treatment outcomes from other resource-limited settings (RLS) may be inaccurate for several biologic and social reasons. A review of the Indian literature is needed to optimize country-specific HIV management and examine these generalizations. MEDLINE and EMBASE were searched for articles published in English by November 2007 on HIV-infected, Indian children (0-18 years) that detailed epidemiology, natural history, or treatment. Articles with original, extractable data were selected and summarized using descriptive statistics. Of 370 citations, 58 studies were included in this review (median study size 24 children). Significant heterogeneity was noted among the studies. HIV infection was reported nearly twice as often in males (male/female ratio 1.9) and diagnosed earlier (4.7 years) than in other RLS. Over 2% of hospitalized children were reported to be HIV-infected. The reported mortality among HIV-infected newborns of 22% at 18 months was lower than other RLS. Improved anthropometrics were the only consistently reported and comparable benefit of short-term HAART to other RLS. Review of the Indian literature yielded potentially unique epidemiology and natural history compared to other RLS. However, important questions about the accuracy and representativeness of the Indian data limit its generalizability and comparability. Targeted interventions to curb India's pediatric HIV epidemic require urgent clarification of these findings. If such differences truly exist, management guidelines should be tailored accordingly.

A recent report suggesting declining HIV transmission rates in southern India has been based on HIV seroprevalence data to estimate HIV incidence. We analyzed HIV incidence rates among 3 cohorts (male female non-sex worker female sex worker [FSW]) presenting to sexually transmitted infection (STI) clinics in Pune India over 10 years. Between 1993 and 2002 consenting HIV-uninfected individuals were enrolled in a prospective study of the risks for HIV seroconversion. Standardized HIV incidence estimates were calculated separately for the 3 cohorts. HIV acquisition risk declined by more than 70% for FSWs (P = 0.02) and men (P < 0.001) attending the STI clinics. There was no significant reduction in HIV incidence among women attending STI clinics (P = 0.74). The decline in HIV acquisition risk among male patients with STIs was associated with an increase in reported condom use with recent FSW contact and a decrease in genital ulcer disease. We report the first direct evidence for a decline in HIV incidence rates in FSWs and male patients with STIs over time. The lack of change in HIV infection risk among non-sex worker women highlights the need for additional targeted HIV prevention interventions. (authors)

A feasibility study for providing single-dose nevirapine (SD-NVP) prophylaxis for prevention of mother-to-child transmission (PMTCT) of HIV infection provided an opportunity to study the emergence of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations as a result of single-dose administration. The study aimed at the detection of NNRTI drug resistance mutations arising as a result of SD-NVP. A total of 19 and 13 samples collected at 48 h and 2 months postpartum, respectively, from infants that were given SD-NVP were studied for the presence of NNRTI drug resistance mutations by PCR amplification and sequencing of the HIV-1 pol gene using HIV proviral DNA. The drug resistance mutational analysis of final sequences was carried out using the Stanford University HIV Drug Resistance database (http://hivdb.stanford.edu/hiv). Mutations associated with NNRTI drug resistance were observed in two (10.5%) and six (46.15%) samples at 48 h and at 2 months, respectively. K103N, one of the most common mutations, was not observed in any of the samples. The emergence of NVP resistance must be weighed against the simplicity, efficacy, and cost effectiveness of SD-NVP prophylaxis in PMTCT settings in developing countries.