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There is some evidence that female sex workers (FSWs) receive greater earnings for providing unprotected sex. In 2003, the landscape of the fight against HIV/AIDS dramatically changed in India with the introduction of Avahan, the largest HIV prevention programme implemented globally. Using a unique, cross-sectional bio-behavioural dataset from 3591 FSWs located in the four Indian states where Avahan was implemented, we estimate the economic loss faced by FSWs who always use condoms. We estimate the causal effect of condom use on the price charged during the last paid sexual intercourse using the random targeting of Avahan as an instrumental variable. Results indicate that FSWs who always use condoms face an income loss of 65% (INR125, US$2.60) per sex act compared to peers providing unprotected sex, consistent with our expectations. The main finding confirms that clients have a preference for unprotected sex and that policies aiming at changing clients’ preferences and at improving the bargaining power of FSWs are required to limit the spread of HIV.

In a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter-variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but not significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a co-infection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time-points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy.

Interferon-α (IFN-α) plays a vital role in combating viral infections especially in the early control after infection. However, the HIV infection has shown substantial level of suppression of IFN-α secretion during initial phase of infection. The reasons behind this impairment are still obscure. As plasmacytoid dendritic cells (pDCs) are the major producers of this cytokine, the mechanisms of HIV-1-mediated suppression of IFN-α production by pDCs using the primary pDCs were explored. The nuclear translocation of the interferon regulatory factor (IRF)-7, a transcription factor for IFN-α genes, is essential for the initiation of IFN-α production in pDCs. The HIV-1-exposed pDCs did not show the translocation of IRF-7 into the nucleus in our experiments. Furthermore, it was also observed that HIV-1 inhibited AKT phosphorylation of PI3K/akt pathway in pDCs, an important step for IRF-7 translocation to nucleus. HIV-1-induced inhibition of AKT phosphorylation and IRF-7 translocation was evident even in the presence of Toll-like receptor-7 agonist stimulation and correlated with IFN-α suppression. The findings suggest that HIV-1 may alter AKT phosphorylation to inhibit the translocation of IRF-7 into pDC nucleus, leading to IFN-α suppression, and this may be the reason for IFN-α abrogation observed in recently infected HIV patients. Understanding of interactions between HIV-1 and signaling pathways leading to IFN-α secretion may provide targets for immune intervention.

OBJECTIVE The activation of effector immune cells at the cervicovaginal mucosa (CVM) might influence the cervical HIV load and thus the secondary transmission; however, limited information is available about the innate effector cells at CVM during HIV infection. In this study, we quantified and assessed the activation of the effector immune cells at the CVM of HIV-infected women with different disease outcomes: nonprogressive HIV disease (LTNPs) and chronic HIV-infected (CHI) and their relationship with cervical viral shedding. METHOD The phenotype and frequency of cytobrush-derived effector immune cells like natural killer cells, T cells, and dendritic cells and their degranulation status (CD107a expression as a surrogate marker of activation) was determined using flow cytometry in age-matched HIV- infected and uninfected women and their association with cervical HIV load was determined. RESULT The frequencies of dendritic cells, CD56, CD56 natural killer cell subsets were similar in both the study groups and also within the HIV-infected women with and without progressive disease. The frequencies of CD56CD16 natural killer cells (P = 0.04) and degranulating CD56 natural killer cells were significantly higher among HIV-infected women (P

Bone marrow stromal cell antigen 2 (BST2) is an interferon induced host restriction factor for HIV-1 that blocks the release of nascent virions from infected T cells. We aimed to characterize BST2 gene variants in HIV-1 positive individuals in Indian cohort and study the association of these variants with disease progression in long term non progressors (LTNPs) and progressors. Archived samples of 32 LTNPs, 17 progressors, and 78 controls were screened for BST2 gene polymorphisms using Sanger's sequencing method. Frequency distribution, survival analysis and bioinformatics tools were used to study the association of BST2 variants with disease progression. Eighteen variants of BST2 gene were observed in Indian cohort. Intronic SNP rs919267T/C (OR = 4.489 [0.8494–27.03], p = .04157) and exonic SNP rs13485C/G (OR = 3.887 [0.8262–25.56], p = .0488) were found to be significantly associated with disease progression. Also, rs13485C/C genotype in combination with rs919267C/T (OR = 9.406 [1.384–111], p = .0085) and rs145303329 Δ19bp (OR = 3.887 [0.826–25.5], p = .048) were found to be significantly associated with disease progression. 19 bp indel rs145303329 and its allele c.1-443_1–442insCGCCCCCAGAC[C/T]CAGGCCC from BST2 promoter also showed association with disease progression (OR = 12.97 [0.9731–850.5], p = .026). Docking of AP2 repressor with above allele showed the total binding energy of LTNPs and progressors to be −2581.42 kcal/mol and −3563.27/−3562.84 kcal/mol respectively. We have identified the novel association of three BST2 gene SNPs; rs919267, rs13485 and indel rs145303329 from Indian cohort to be associated with the risk of HIV-1 disease progression for the first time.

Under India’s National AIDS Control Program (NACP), WHO recommended strategy of using three rapid tests is adopted for diagnosis of HIV in an asymptomatic individual. Since the NACP has a stringent kit evaluation procedure and due to the availability of newer third generation Rapid Diagnostic Tests (RDTs) it may be possible to adapt two test strategy for HIV diagnosis instead of the recommended three test strategy. The authors reviewed programmatic data on HIV testing to explore whether use of two rapid tests for HIV diagnosis as against three tests could be a feasible approach without compromising the quality and readability of testing. Data on the HIV diagnosis performed on serum specimens collected for the period of one year (2011-12) from 82 Integrated Testing and Counselling Centers (ICTCs) or Prevention of Parent to Child Transmission Centers (PPTCTs) associated with State reference Laboratories (SRLs) was analysed. Out of 654258 results that were analysed 25168 (3.84%) specimens were positives. It was observed that both two and three test algorithms provided similar results for majority (>99%) of the HIV positive specimens. Discordance was observed in labelling of specimen with inconclusive status (N = 21), however the true status of these samples could not be obtained. The analysis indicated that the use of two test algorithm will have programmatic benefits in terms of reduced financial burden to the programme and ease of procurement, shipment and storage before and after distribution without comprising the quality of the testing. The prospective study would confirm this observation.

Plasmacytoid dendritic cells (pDCs) play an important role in innate immune response against viruses, mainly through interferon-α (IFN-α) secretion. Impaired IFN-α secretion has been observed in patients with acute human immunodeficiency virus type 1 (HIV-1) infection and the reasons for this impairment are still obscure. To know the grounds behind this situation, HIV-1 viral copy numbers similar to those found in primary HIV-1 infection were used to stimulate peripheral blood mononuclear cells (PBMCs) and pDCs in this study. Intracellular IFN-α production was seen as early as 2 h in pDCs with TLR-7 agonist (imiquimod) stimulation, but HIV-1 required 48 h to induce secretion of IFN-α in supernatants and it was 10 times less compared to imiquimod. Thus, it shows that HIV-1 delays and impairs IFN-α production from pDCs. Furthermore, the IFN-α inhibitory activity of HIV-1 was checked by stimulating PBMCs and pDCs with imiquimod either simultaneously with HIV-1 or after 2 h pre-exposure to HIV-1. Pre-exposure to HIV-1 resulted in significant reduction in IFN-α secretion by pDCs and PBMCs when compared to imiquimod alone. In addition, simultaneous stimulation of these populations with HIV-1 and imiquimod resulted in significant impairment in IFN-α production in pDCs but not in PBMCs. HIV-1 not only fails to induce IFN-α in adequate quantities but also inhibits IFN-α secretary capacity of pDCs. HIV-1 particles were found to bind CD303 receptor on pDC surface probably blocking initiation of cascade leading to IFN-α impairment. The understanding of the pathways that lead to this suppression may help in devising the HIV control strategies.

Although HIV-1 epidemic in India is mainly driven by subtype C, subtype A has been reported for over two decades. This is the first comprehensive analysis of sequences of HIV-1 subtype A from India, based on the near full-length genome sequences of six different HIV-1 subtype A Indian isolates along with available partial gene sequences from India and global sequences. The phylogenetic analyses revealed the convergence of all Indian whole-genome sequences and majority of the partial gene sequences to a single node with the sequences most closely related to African sub-subtype A1. The presence of the signature motifs consistent with those observed in subtype A and CTL epitopes characterized specifically for subtype A1 were observed among the study sequences. Deletion of LY amino acid of LYPXnL motif of p6gag and one amino acid in V3 loop have been observed among the study isolates, which have also been observed in a few sequences from East Africa. Overall, the results are indicative of a monophyletic lineage or founder effect of the Indian epidemic due to sub-subtype A1 and supportive of a possible migration of subtype A1 into India from East Africa.

Background and objectives: Respondent-driven sampling (RDS) is widely used to sample hidden populations and RDS data are analyzed using specially designed RDS analysis tool (RDSAT). RDSAT estimates parameters such as proportions. Analysis with RDSAT requires separate weight assignment for individual variables even in a single individual; hence, regression analysis is a problem. RDS-analyst is another advanced software that can perform three methods of estimates, namely, successive sampling method, RDS I and RDS II. All of these are in the process of refinement and need special skill to perform analysis. We propose a simple approach to analyze RDS data for comprehensive statistical analysis using any standard statistical software. Methods: We proposed an approach (RDS-MOD - respondent driven sampling-modified) that determines a single normalized weight (similar to RDS II of Volz-Heckathorn) for each participant. This approach converts the RDS data into clustered data to account the pre-existing relationship between recruits and the recruiters. Further, Taylor's linearization method was proposed for calculating confidence intervals for the estimates. Generalized estimating equation approach was used for regression analysis and parameter estimates of different software were compared. Results: The parameter estimates such as proportions obtained by our approach were matched with those from currently available special software for RDS data. Interpretation & conclusions: The proposed weight was comparable to different weights generated by RDSAT. The estimates were comparable to that by RDS II approach. RDS-MOD provided an efficient and easy-to-use method of estimation and regression accounting inter-individual recruits’ dependence.

In the current study we investigated the prevalence of the TNF-α 238G/A single nucleotide polymorphism (SNP) of the TNF-α gene in the development of lipodystrophy among HIV-1 infected individuals who had been receiving antiretroviral therapy (ART) in the immunodeficiency clinics of the National AIDS Research Institute (NARI) at Pune, India. We assessed the association of this SNP with the development of lipoatrophy/dyslipidemia and insulin resistance in these patients and measured carotid intima thickening which is a surrogate marker for chronic cardiac morbidity. Our results show that the incidence of the TNF-α 238G/A SNP is ~ two fold higher in patients with lipodystrophy as compared to those without lipodystrophy. Patients with lipodystrophy demonstrated a higher likelihood of the development of metabolic syndrome as evident by increased insulin sensitivity and increased percentage (%) β cell function. Further, a significant increase in left carotid intima thickness was observed in patients with lipodystrophy. Our study validates the association of the TNF-α 238G/A SNP allelic variant with the development of HIV- lipodystrophy via the modulation of TNF-α production, which contributes to dyslipidemia, increased lipolysis, increased insulin resistance, altered differentiation of adipocytes and increased carotid intima thickness. The contribution of genetic determinants such as the TNF-α 238G/A SNP to lipodystrophy, may provide insight into the mechanisms that underlie this disease condition and may be useful in the future for personalized therapy. Additionally, these findings will be useful in monitoring chronic cardiac morbidities among HIV infected individuals who express this SNP.

objective To investigate associations between background characteristics (psychosocial adversity, risk behaviours/perception of risk and HIV-related knowledge, perceptions and beliefs) and psychological and cognitive morbidity among people coming for testing for HIV/AIDS in Goa, India. methods Analysis of cross-sectional baseline data (plus HIV status) from a prospective cohort study. Participants were recruited at the time of coming for HIV testing. results Consistent with associations found among general population samples, among our sample of 1934 participants, we found that indicators of psychosocial adversity were associated with CMD (common mental disorder – major depression, generalised anxiety and panic disorder) among people coming for testing for HIV. Similarly, perpetration of intimate partner violence was associated with AUD (alcohol use disorder). Two STI symptoms were associated with CMD, and sex with a non-primary partner was associated with AUD. Suboptimal knowledge about HIV transmission and prevention was associated with low cognitive test scores. In contrast with other studies, we found no evidence of any association between stigma and CMD. There was no evidence of modification of associations by HIV status. conclusions Among people coming for testing for HIV/AIDS in Goa, India, we found that CMD occurred in the context of social and economic stressors (violence, symptoms of STI, poor education and food insecurity) and AUD was associated with violence and risky sexual behaviour. Further research is necessary to understand the role of gender, stigma and social norms in determining the relationship between sexual and mental health. Understanding associations between these background characteristics and psychological morbidity may help inform the design of appropriate early interventions for depression among people newly diagnosed HIV/AIDS.

Manipur is a geographically isolated state of India characterised by a high HIV prevalence among people who inject drugs (PWID). A low-to-moderate lifetime rate of HIV testing has been documented amongst PWID in Manipur. Little is known about the extent of undiagnosed HIV in this setting and whether uptake of HIV testing (and knowledge of a positive diagnosis) leads HIV-positive PWID to change their risk behaviours. The cross-sectional data (n = 821) analysed for this paper were collected in 2009 for the Integrated Behavioural and Biological Assessment (IBBA) using interviewer-administered questionnaires and the collection of de-linked blood and urine samples. Almost one-third (30.7%) of the participants tested HIV positive. The majority knew where to obtain a confidential HIV test (80.7%), however, half of the HIV-positive participants had either never had an HIV test (37.7%), or had undertaken a test without collecting the result (12.7%). Almost one-quarter (23.4%) of the HIV-positive participants and 17.4% of the HIV-negative participants had shared a needle/syringe with at least one other injector during the preceding month. Encouragingly, HIV-positive participants were significantly more likely than HIV-negative participants to use condoms with their regular sexual partners, however, there was still a high proportion of HIV-positive participants who did not use a condom at last sex with their regular (47.2%) or casual (48.0%) partners. Having taken an HIV test and collected the result was associated with a reduction in HIV-risk behaviours among HIV-positive participants, but not among HIV-negative participants. In conclusion, we found that a substantial proportion of the HIV-positive PWID in Manipur were not aware of their positive status, and risky injecting and sexual practices were commonplace. However, HIV-positive PWID appear to reduce their high-risk behaviours when they become aware of their HIV status highlighting the importance of taking HIV testing coverage to scale.

The TNF-α-238G/A single nucleotide polymorphism (SNP) independently increases the risk of lipodystrophy progression. The current study evaluates the contribution of the different antiretroviral treatments (ART) regimens administered to HIV infected individuals in Pune to the development of lipodystrophy and insulin resistance in patients having TNF-α-238G/A polymorphism. A total of 172 HIV-1 infected patients were enrolled in the study and were subdivided into patients with [HIV+LIPODYS+ (cases)] and without lipodystrophy [HIV+LIPODYS- (controls)]. We assessed the contribution of the typical 2NRTI+1 NNRTI based ART regimens prescribed in our clinics with the development of dyslipidemia and insulin resistance in both the above study group. A significantly higher percentage of patients with lipodystrophy expressed the TNF-α-238G/A polymorphism. Significant correlations were observed between Adiponectin, TNF-α protein levels and type of ART-ART regimen. Our results showed that the NNRTI efavirenz contributed more to the lipodystrophy syndrome as compared to other antiretroviral drugs tested. The TNF-α 238G/A SNP contributes to changes in insulin sensitivity and lipodystrophy. Key words: HIV-1, antiretroviral drugs, single nucleotide polymorphism, lipodystrophy, dyslipidemia, adiponectin, insulin resistance, metabolic syndrome.

Tumor growth factor (TGF)-β1 is a cytokine with potent immunoinhibitory functions and is known to be secreted by vaginal epithelial cells. The present study was designed to determine the association of cervicovaginal levels of TGF- β1 with various innate immune secretions such as cytokines and antimicrobial polypeptides [Trappin-2/Elafin and secretory leukocyte protease inhibitor (SLPI)] and cervical HIV shedding in HIV-infected Indian women. TGF- β1, antimicrobial polypeptides, and cytokine levels were estimated in the cervicovaginal lavages (CVLs) of 36 age-matched HIV-infected and 31 HIV-uninfected asymptomatic Indian women using an ELISA and Bio-Plex Assay, respectively. The nonparametric Mann-Whitney test and Spearman's test were used to compare the levels from both the groups and to determine the association of the TGF-β1 levels with cervical viral shedding and antimicrobial peptides. The levels of Trappin-2/Elafin and SLPI were similar in the CVLs of HIV-infected and HIV-uninfected women, but were significantly associated with a low cervical viral load (r=-0.501, p=0.005 for Trappin-2/Elafin and r=-0.488, p=0.007 for SLPI). Eleven (30.5%) of the 36 HIV-infected women showed 5- to 30-fold higher levels of TGF-β1 as compared to the levels in uninfected women. The TGF-β1 levels were significantly associated with higher cervical viral load (r=0.425, p=0.03) and with lower levels of Trappin-2/Elafin (r=-0.407, p=0.03) and SLPI (r=-0.405, p=0.04). The findings indicate a possible interdependent mechanism driving the identified higher TGF-β1 and lower antimicrobial peptide (Trappin-2/Elafin and SLPI) levels at the genital mucosa surface in HIV-infected women. We postulate that a combination of increased TGF-β1 secretion and altered levels of Trappin-2/Elafin and SLPI contributes to increased HIV shedding. The observation warrants further studies to identify the underlying mechanisms linking increased mucosal TGF-β1 levels and genital HIV shedding. Considering the known association of HIV and cervical cancers, it will also be important to assess the predictive capacity of TGF-β1 levels in HIV-associated cervical malignancies.

A series of novel thiazolidin-4-one analogues, characterized by different substitution patterns at positions C-2 and N-3 of the thiazolidin-4-one scaffold for anti-HIV-1 activity has been investigated. Most of the compounds showed anti-HIV-1 activity at micromolar concentrations when tested in TZM-bl cells in vitro. Among the thirty-three compounds tested, compound 16 was the most potent inhibitor of HIV-1 replication against HIV-1IIIB, HIV-1ADA5, HIV-1UG070 and HIV-1VB59 (EC50 = 0.02, 0.08, 0.08 and 0.08 μM, respectively) with selectivity index (SI = 6940, 1735, 1692 and 1692) against tested viral strains, respectively. The results of the present study suggested that the substitution of the nitro group at 6′ position of the C-2 phenyl ring and 4,6-dimethylpyridin-2-yl at the N-3 position of thiazolidin-4-one had a major impact on the anti-HIV-1 activity and was found to lower cytotoxicity. The substitution of the heteroaryl ring with bromo group and bicyclic heteroaryl ring at N-3 thiazolidin-4-one was found to lower anti-HIV-1 activity and increase cytotoxicity. The undertaken docking studies thus facilitated the identification of crucial interactions between the HIV-1 RT enzyme and thiazolidin-4-one inhibitors, which can be used to design new potential inhibitors.

A multilevel analysis of 2 surveys (2005, 2009) among female sex workers in India shows that increased prevention program coverage between surveys was associated with a decrease in HIV prevalence., Background As one way of assessing the impact of Avahan, the India AIDS Initiative of the Bill & Melinda Gates Foundation, we examined the association between HIV prevention program indicators and changes in HIV prevalence among female sex workers (FSWs) between 2005 and 2009. Methods We conducted a secondary data analysis from 2 large cross-sectional surveys (2005–2006 and 2008–2009) across 24 districts in south India (n = 11,000 per round). A random-effect multilevel logistic regression analysis was performed using HIV as the outcome, with individual independent variables (from both surveys) at level 1 and district-level FSW-specific program indicators and contextual variables at level 2. Program indicators included their 2006 value, the difference in their values between 2008 and 2006, and the interaction between this difference and study round. Results HIV prevalence among FSWs decreased from 17.0% to 14.2% (P < 0.001). This decline varied significantly (P = 0.006) across levels of difference in program coverage (% of FSWs contacted by the program in a given year). Odds ratios comparing HIV prevalence between rounds changed with the level of increase in coverage and were statistically significant with coverage increase ≥ quartile (Q) 1: odds ratio, 0.85 at Q1; 0.78 at Q2; 0.66 at Q3; and 0.51 at Q4. Conclusions These findings suggest that increased program coverage was associated with declining HIV prevalence among FSWs covered by the Avahan program. The triangulation of our results with those from other approaches used in evaluating Avahan suggests a major impact of this intervention on the HIV epidemic in southern India.

Objective To assess the impact of the Avahan HIV prevention programme for female sex workers (FSWs) in south India on reducing syphilis prevalence among their clients, by comparing rates of syphilis over time as reported in two large-scale surveys of FSWs’ clients. Methods A random-effect multilevel logistic regression analysis was performed using syphilis as the dependent variable, with individual independent variables (from the two survey rounds) at level 1 and the district-level programme (from the Avahan computerised monitoring and information system) and contextual variables (from Indian government datasets) at level 2. Programme variables included their 2006 value and their difference in value between 2008 and 2006, as well as the interaction between the latter and the study round. The analysis also controlled for baseline syphilis prevalence and its interaction with the study round. Results Syphilis decreased significantly among FSWs’ clients, from 4.8% (round 1) to 2.6% (round 2), p

Quality of life including the domains of physical health and mental health are influenced by HIV infection. Coping strategies and their relationships with various domains of quality of life (QOL) were assessed among 97 HIV-infected individuals in Pune, India. Most of the infected individuals adopted emotion-focused strategies through cognitive reframing and acceptance of their HIV status. One-third adopted problem-focused coping and sought health care, scientific information and social support. Significant associations of coping strategies were observed with marital status and work and earning domains of the QOL questionnaire. Findings can help decide appropriate care and support strategies and psycho-social interventions for HIV-infected individuals.

Background: India has scaled up ART programme very rapidly. Though there are reports on retention of patients in the national programme, data on transfer out patients within the ART centers are scanty in India. Methods: This is a retrospective study of patients receiving antiretroviral treatment between January 2006 and July 2013. The patients who were transferred out from the ART center at National AIDS Research Institute in Pune were included in the study. The data on whether they reached the respective ART centers were collected either by making telephonic calls to the patients and/or to the respective ART centers. Results: Of the total 3015 patients ever started on treatment from the ART center, 158 (5.24%) were transferred out to other ART centers. Of these, 123 (77.8%) patients reached other centres and they were “transferred in”. However, 15 (9.5%) did not reach to respective ART centers and information could not be obtained for 20 (12.7%) transferred out patients. The analysis showed that those who were not living with their partners were 4.53 times more likely to not to reach the preferred ART centre after taking transfer [OR, 95% CI: (1.24 - 16.51), p = 0.022]. Conclusion: Our data suggest that significant number of transfer out patients is lost in HIV treatment cascade. Considering the total PLHIV on treatment in the country, this group adds significantly to the burden of lost to follow up patients. It is important to strengthen the system of tracking the transfer out patients in the programme which will help in patching an important leak in the cascade of HIV care.

This paper examines the association between alcohol use and HIV-related sexual risk behaviors among men who have sex with men (MSM). A cross-sectional bio-behavioral survey was conducted among 3,880 MSM, recruited using time-location cluster sampling from cruising sites in three Indian states. Nearly three-fifths of the participants reported alcohol use. Among frequent users (40 % of the sample), defined as those who consumed alcohol daily or at least once a week, 66 % were aged 25 years and above, 53 % self-identified as kothi (feminine/receptive), and 63 % consistently used condoms with male paying partners. Multivariate logistic regression demonstrated that frequent users were more likely to be aged 25 years and above, less likely to self-identify as kothi, and less likely to consistently use condoms with male paying (AOR = 0.7; 95 % CI 0.5–0.9) and male regular (AOR = 0.7; 95 % CI 0.6–0.9) partners. HIV prevention interventions for MSM need to provide tailored information on alcohol use-related sexual risk, especially for MSM in sex work and MSM with male regular partners.

Summary Background Avahan, the India AIDS initiative of the Bill & Melinda Gates Foundation, was a large-scale, targeted HIV prevention intervention. We aimed to assess its overall effectiveness by estimating the number and proportion of HIV infections averted across Avahan districts, following the causal pathway of the intervention. Methods We created a mathematical model of HIV transmission in high-risk groups and the general population using data from serial cross-sectional surveys (integrated behavioural and biological assessments, IBBAs) within a Bayesian framework, which we used to reproduce HIV prevalence trends in female sex workers and their clients, men who have sex with men, and the general population in 24 South Indian districts over the first 4 years (2004–07 or 2005–08 dependent on the district) and the full 10 years (2004–13) of the Avahan programme. We tested whether these prevalence trends were more consistent with self-reported increases in consistent condom use after the implementation of Avahan or with a counterfactual (assuming consistent condom use increased at slower, pre-Avahan rates) using a Bayes factor, which gave a measure of the strength of evidence for the effectiveness estimates. Using regression analysis, we extrapolated the prevention effect in the districts covered by IBBAs to all 69 Avahan districts. Findings In 13 of 24 IBBA districts, modelling suggested medium to strong evidence for the large self-reported increase in consistent condom use since Avahan implementation. In the remaining 11 IBBA districts, the evidence was weaker, with consistent condom use generally already high before Avahan began. Roughly 32 700 HIV infections (95% credibility interval 17 900–61 600) were averted over the first 4 years of the programme in the IBBA districts with moderate to strong evidence. Addition of the districts with weaker evidence increased this total to 62 800 (32 000–118 000) averted infections, and extrapolation suggested that 202 000 (98 300–407 000) infections were averted across all 69 Avahan districts in South India, increasing to 606 000 (290 000–1 193 000) over 10 years. Over the first 4 years of the programme 42% of HIV infections were averted, and over 10 years 57% were averted. Interpretation This is the first assessment of Avahan to account for the causal pathway of the intervention, that of changing risk behaviours in female sex workers and high-risk men who have sex with men to avert HIV infections in these groups and the general population. The findings suggest that substantial preventive effects can be achieved by targeted behavioural HIV prevention initiatives. Funding Bill & Melinda Gates Foundation.

Cytokines and chemokines are the cell signaling proteins which are considered as important biomarkers of inflammation and immunity. However the fragile nature of these markers results in the concentration variation due to various external factors. We assessed the influence of commonly used anticoagulants (EDTA and heparin) on various cytokine levels from 32 paired plasma samples using highly sensitive multiple cytokine estimation assay. Out of 17 cytokines estimated, 15 were detectable in more than 80% of the samples from both the groups. TNF-α, IFN-γ, IL-4, IL-5, and G-CSF levels were significantly higher (p values0.05 for all) in plasma with EDTA, whereas the levels of IL-6, IL-8, IL-10, IL-17, MIP-1β, GM-CSF and MCP-1 were found to be significantly higher (p values0.05 for all) in plasma with heparin. There was no significant difference in the levels of IL-7, IL-12 (P70) and IL-13 in both the groups. The study showed that the anticoagulants significantly affect the measurement of certain cytokines. Hence, it is important to choose an appropriate anticoagulant before the estimation of cytokines for reliable use of plasma cytokines as biomarkers in patient management.

HIV-specific antibody-dependent cell cytotoxicity (ADCC) is likely to be important in governing protection from human immunodeficiency virus (HIV) and slowing disease progression. Little is known about the ADCC responses to HIV-1 subtype C. We characterized ADCC responses in HIV-1 subtype C-infected Indian subjects with slow disease progression and identified the dominant antigenic regions recognized by these antibodies. ADCC responses were measured in plasma from 34 long-term non-progressors (LTNPs), who were asymptomatic and maintained CD4 count above 500 cells/mm3 for the last 7 years in the absence of antiretroviral therapy (ART), and 58 ART naïve progressors with CD4 count

Rapid emergence of drug resistance is crucial in management of HIV infection limiting implementation of efficacious drugs in the ART regimen. Designing new molecules against HIV drug resistant strains is utmost essential. Based on the anti-HIV-1 activity, we selected four 4-thiazolidinone derivatives (S009-1908, S009-1909, S009-1911, S009-1912) and studied their interaction with reverse transcriptase (RT) from a panel of 10 clinical isolates (8 nevirapine resistant and two susceptible) using in silico methods, and inhibition pattern using in vitro cell based assays. On the basis of binding affinity observed in in silico analysis, 2-(2-chloro-6-nitrophenyl)-3-(4, 6-dimethylpyridin-2-yl) thiazolidin-4-one (S009-1912) was identified as the lead molecule followed by S009-1908, S009-1909 and S009-1911. The in vitro activity against the same panel was assessed using TZM-bl assay (IC50: 0.4–11.44 µg/ml, TI: 4–126) and subsequently in PBMC assay against a nevirapine resistant clinical isolate (IC50: 0.8–6.65 µg/ml, TI: 8.31–11.43) and standard strain from NIH ARRRP (IC50: 0.95–3.6 µg/ml, TI: 9–26). The study shows analogue with pyrimidin-2-yl amino substitution at N-3 position of thiazolidin-4-one ring (S009-1908, S009-1909, S009-1911) exhibited enhanced activity as compared to pyridin-2-yl substituted derivatives (S009-1912), suggesting the use 4-thiazolidinones for developing potent inhibitors against HIV-1 drug resistant strains.

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.

This case series reports three infants diagnosed with HIV-1 infection using DNA polymerase chain reaction (PCR) testing. The three children were initiated on antiretroviral therapy (ART) at ten, four and six months of age. Their serological tests at 18 months of age were negative for HIV-1. The first child was discontinued from ART. The other two children were HIV-negative after 18 months, but were continued on ART. Such seroreversion may be either due to viral suppression or false-positive DNA PCR results. There is a need to develop guidelines to address such discordant cases.

The first cases of HIV infection in India were detected in 1986 among female sex workers in Chennai. A rapid increase followed in many states. The current national prevalence is about 0.26% compared with a global average of 0.2%, but the figure in most high-risk groups including female sex workers is much higher (up to 7%). New HIV infections reached a peak in 1998 and have since declined by 60%, although the total number of HIV-positive persons remains stable at 2.1 million, largely probably due to the increased life expectancy following antiretroviral therapy. The Indian epidemic is characterized by low levels in the general population and elevated concentrations among high-risk groups. Transmission is mainly heterosexually driven, with differential burdens across the states. The four main drivers of HIV infection in India differ in order from those elsewhere in the world and are commercial sex work, general heterosexual intercourse, injecting drug use and unprotected anal sex between men who have sex with men. There are distinct differences from state to state in the prevalence of HIV, with some around the national norm of 0.21% but others with over 1% infected. India has embarked on a targeted HIV prevention strategy in recent years which is strongly associated with a fall in infection rate in both low- and high-risk groups.

In the present study, we investigated genetic divergence between complete autologous HIV-1 env genes amplified directly from plasma of two antiretroviral-naive, slow progressing Indian patients with broad neutralizing antibody response. All the envelope (Env) clones obtained from one patient (LT1) belonged to subtype C; the second patient (LT5) harbored quasispecies comprised of pure B, C, and B/C recombinants with distinct breakpoints indicative of dual infection with genetically distinct strains. Further characterization of these Envs would provide insight into the biological properties under strong humoral immune response.

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

The World Health Organizations HIV Drug Resistance (WHO HIVDR) Threshold survey method was used to assess transmitted HIVDR in newly diagnosed HIV-1-infected primigravida women attending the Prevention of Parent to Child Transmission (PPTCT) centers in Kakinada, in whom it is likely that the infection had recently occurred. Out of the 56 consecutively collected eligible specimens, 51 were tested using the ViroSeq RT-PCR method (Abbott Germany) to obtain 47 consecutive sequences for the HIV-1 protease (PR) and reverse transcriptase (RT) region. As per the 2009 WHO list of mutations for surveillance of transmitted HIVDR, only one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation was detected at K101E from all specimens tested, suggesting a low prevalence (5%) of resistance to NNRTIs and no mutations were detected at other sites, suggesting a low prevalence (5%) of resistance to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) drug classes as well. Phylogenetic analysis showed all sequences belonged to HIV-1 subtype C. In the wake of antiretroviral treatment (ART) scale-up, future evaluation of transmitted HIVDR is essential in Kakinada as well as in other regions of India.

The study was carried out to assess the factors associated with HIV seropositivity among female sex workers (FSWs) in Dimapur, Nagaland, a high HIV prevalence state of India. A total of 426 FSWs were recruited into the study using respondent driven sampling (RDS). Data on demographic characteristics, sexual and injecting risk behaviours were collected from them and were tested for HIV, Syphilis, Neisseria gonorrhoeae and Chlamydia trachomatis. RDS-weighted univariate and multivariate logistic regression analysis was performed to assess the factors associated with HIV seropositivity. Consistent condom use with regular and occasional sexual clients was 9% and 16.4%, respectively. About 25% of the participants ever used and 5.7% ever injected illicit drugs. RDS adjusted HIV prevalence was 11.6%. In the univariate analysis, factors associated with HIV were initiating sexual intercourse before the age of 15 years, ≥2 years duration of sex work, serving clients at lodge/hotel, positive test result for one or more sexually transmitted infections (STIs), lifetime history of injecting drug use, lifetime history of consuming illicit drugs, ever having exchanged sex for drugs, having sexual partners who engaged in risky injecting practices and having been widowed or divorced. In multivariate analysis, factors found to be independently associated with HIV included lifetime injecting drug use, initiating sexual intercourse before the age of 15 years, positive test result for one or more STIs and having been widowed. Injecting drug use was found to be most potent independent risk factor for HIV (OR: 3.17, CI: 1.02-9.89). Because of lower consistent condom use among them, FSWs may act as bridge for HIV transmission to general population from injecting drug users (IDU) through their sexual clients. The informations from this study may be useful for enriching the HIV preventions effort for FSWs in this region.

Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4–2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped viruses to autologous and heterologous plasma antibodies. When tested against monoclonal antibodies targeting different sites in gp120 and gp41, Envs expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.

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.

Problem statement: The presence of a p6 domain at the C-terminus of the Gag polyprotein is a characteristic feature of HIV-1 and other primate lentiviruses. The p6Gag protein is considered as a major phosphoprotein in mature HIV-1 virions and is involved in the viral assembly and budding process. Sequence variation in the p6gag region in HIV-1 has been associated with changes in viral replication capacity and antiretroviral drug susceptibility. Approach: We examined sequence variation in the HIV-1 p6gag region using 38 isolates or infected Peripheral Blood Mononuclear Cells of HIV-1 subtype C and 20 additional Indian subtype C gag sequences from the Los Alamos database. Different patterns of insertions and deletions were observed in different motifs present in the p6 region. PTAP duplication was found in three strains. Results: We found PAP/TAP/LEPTAP/LPTVPTAP/ PAVPAAP like insertions at PTAP duplication site. KQE motif (84%) was observed as one of the most conserved motif in p6Gag while LYP motif was absolutely absent in Indian clade C sequences. Insertion of T/H/TT /PYRE/PYKE/EPKDRE was found instead of LYP motif. Conclusion: Further studies are needed to determine whether p6gag polymorphisms found in different motifs influence viral replication capacity, antiretroviral drug susceptibility, or other phenotypic properties of these strains.

Objective This paper evaluates Avahan programme9s coverage of female sex workers (FSWs), focus on high-risk FSWs and intermediate outcomes. Methods First round of cross-sectional survey data, Integrated Behavioral and Biological Assessments (IBBA), conducted in 22 districts, were aggregated into district categories: Solo, where Avahan was the sole service provider covering all FSWs and Major or Minor where Avahan was not the sole provider, but intended coverage was >50% or ≤ 50% of FSWs respectively. Multivariate logistic regression was applied to compare exposure by district categories, vulnerability factors and intermediate outcomes associated with exposure. Results Reported exposure, evaluated on basis of having received any of three core services, was higher in Solo (75%) compared with Minor (66%) districts. Logistic regression showed that FSWs in solo districts were more likely to be exposed (adjusted odds ratio (AOR)=1.5; 95% CI 1.20 to 1.86) compared with FSWs in Minor districts. Multivariate analysis in Solo districts revealed that FSW with ≥15 clients in the past week had a higher chance of being exposed to core services (AOR=1.56; 95% CI 1.03 to 2.35). Exposure to the three services in Solo Avahan districts was significantly associated with correct knowledge on condom use (AOR=1.36; 95% CI 1.05 to 1.78), consistent condom use with occasional clients (AOR=3.17; 95% CI 2.17 to 4.63) and regular clients (AOR=2.47; 95% CI 1.86 to 3.28) and STI treatment-seeking behaviour (AOR=3.00; 95% CI 1.94 to 4.65). Conclusions Higher coverage of FSWs was achieved in districts where Avahan was the only intervention compared with districts having multiple and longstanding non-Avahan programmes. Exposure in Solo districts was associated with intermediate outcomes; this need to be further evaluated in comparison with non Avahan areas and substantiated through data from next IBBA.

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.

The mucosal immune system acts as a first line of defense against infection caused by luminal pathogens. Because HIV is transmitted primarily via mucosal associated tissues, particularly with sexual transmission, understanding antiviral immunity present at these sites is important. As most of the peptide antigens show poor immunogenicity when immunized alone but after incorporating the same peptide antigens along with adjuvant CpG ODN in microparticles has shown enhanced immunogenicity in the murine model. In the present study we have investigated the immunomodulatory effects of two adjuvants, CpG 1826 and CpG 2006 (Class B, Also known as type K) to the four peptide antigens of HIV such as envelope glycoproteins gp41 Leucine Zipper, gp41 fusion domain and gp120-C2 as well as regulatory protein (Nef) in microparticles, exploring nasal route with single immunization schedule. Peptide (s) alone in the microparticles elicited low peptide specific IgG and IgA peak titres in the sera, whereas the inclusion of CpG ODN with peptides in microparticles significantly enhanced peptide specific IgG and IgA peak titres and such responses were sustained for longer durations. Similarly higher SIgA response was achieved in the mucosal washes with CpG encapsulated in microparticles. Such presence of SIgA in washes was further correlated with the presence of secretory component (SC) in the respective washes. Both adjuvants induced excellent peptide specific IgG and IgA immune responses. Thus the overall study highlighted the importance of CpG ODNs as a mucosal adjuvant for weaker peptide antigens and thus can explore for developing peptide based vaccine against HIV.

Little is known about the neutralization properties of HIV-1 in India to optimally design and test vaccines. For this reason, a functional Env clone was obtained from each of ten newly acquired, heterosexually transmitted HIV-1 infections in Pune, Maharashtra. These clones formed a phylogenetically distinct genetic lineage within subtype C. As Env-pseudotyped viruses the clones were mostly resistant to IgG1b12, 2G12 and 2F5 but all were sensitive to 4E10. When compared to a large multi-subtype panel of Env-pseudotyped viruses (subtypes B, C and CRF02_AG) in neutralization assays with a multi-subtype panel of HIV-1-positive plasma samples, the Indian Envs were remarkably complex antigenically. With the exception of the Indian Envs, results of a hierarchical clustering analysis showed a strong subtype association with the patterns of neutralization susceptibility. From these patterns we were able to identify 19 neutralization cluster-associated amino acid signatures in gp120 and 14 signatures in the ectodomain and cytoplasmic tail of gp41. We conclude that newly transmitted Indian Envs are antigenically complex in spite of close genetic similarity. Delineation of neutralization-associated amino acid signatures provides a deeper understanding of the antigenic structure of HIV-1 Env.

Objective: To report HIV and sexually transmitted infection (STI) prevalence and sexual behaviour of long-distance truckers on four national highway routes from a large, cross-sectional, national-level trucker survey in India. Methods: Seven trans-shipment locations covering the bulk of India’s transport volume along four routes, north-west (NW), north-south (NS), north-east (NE) and south-east (SE) were identified as survey sites. A total of 2066 long-distance truckers were selected using a two-stage, time–location cluster sampling approach and, after consent, interviewed about their sexual behaviour. Urine and blood sample were tested for selected STIs. Results: Overall, HIV prevalence among truckers was found to be 4.6%, with prevalence highest on the SE route (6.8%) and lowest on the NS (2.4%). Positive HSV-2 serology, which was tested in a 10% subsample, was low along three routes, 10.0%, 12.8% and 6.7% for the NE, NS and NW, respectively, but 38.7% in the SE. The truckers from the SE were found to be more likely to have sex with paid partners than the NE route. Moreover, truckers who owned their trucks were more likely than those who did not use condoms consistently with paid partners, and truckers who drive trucks owned by their relatives/friends are more likely than others to have any STI. Conclusions: Low self-risk perception for HIV (9.9%), low consistent condom use with non-paid partners (18.6%) and wives (3%), low reported exposure to any interventions (25.6%) and low levels of ever having taken an HIV test (16.5%) make truckers an important bridge population requiring strengthened interventions.

OBJECTIVE: In four states in southern India we explored the determinants of HIV prevalence among female sex workers (FSW) as well as factors associated with district-level variations in HIV prevalence among FSW. METHODS: Data from cross-sectional surveys in 23 districts were analysed with HIV prevalence as the outcome variable and sociodemographic and sex work characteristics as predictor variables. Multilevel logistic regression was applied to identify factors that could explain variations in HIV prevalence among districts. RESULTS: HIV prevalence among the 10 096 FSW surveyed was 14.5% (95% confidence interval 14.0-15.4) with a large interdistrict variation ranging from 2% to 38%. Current marital status and the usual place of solicitation emerged as important factors that determine individual probability of being HIV positive as well as the HIV prevalence within districts. In multivariate analysis compared with home-based FSW the odds of being HIV positive was greater for brothel-based FSW [adjusted odds ratio (AOR) 2.17 P

OBJECTIVE: To describe and compare sexual and injecting risk behaviours and sexually transmitted infections (STI) hepatitis C virus (HCV) and HIV prevalence in injecting drug users (IDU) in six districts in three states of India: Manipur Nagaland and Maharashtra. METHOD: The respondent-driven sample consisted of 2075 IDU. Consenting participants were administered a structured questionnaire and samples of blood and urine were collected to test for HIV and STI. Data were analysed using RDSAT. RESULTS: In two districts in Manipur 77 and 98% of IDU injected heroin whereas the main injecting drug in Nagaland was dextropropoxyphene (99%). In Mumbai/Thane Maharashtra the majority of respondents reported using chlorpheniramine (87%) and heroin (99%). In all districts almost half of IDU reported generally sharing needles and syringes; consistent condom use with non-paid female partners was also low. Approximately one-quarter of IDU in Mumbai/Thane visited a paid partner in the past year. IDU with reactive syphilis serology were higher in Nagaland (7 and 19%) than in Manipur and Maharashtra. HIV in two districts of Manipur (23% 32%) and Mumbai/Thane (16%) was greater than Nagaland (

The year 1986 saw first case of HIV infection as well as first report of AIDS case in India. Since then the epidemic has spread throughout the country. In the recent years there is evidence of epidemic being stabilized with decrease in new infections reported from some parts of the country. The absolute number of HIV infections in the country is expected to be close to 2.5 million and National AIDS Control Programme, phase III is geared to contain the epidemic. HIV viruses circulating in India predominantly belong to HIV-1 subtype C. However, there have been occasional reports of HIV-1 subtype A and B. Matter of concern is reports of A/C and B/C mosaic viruses that are being reported from different parts of the country. The data on HIV drug resistance from India is rather limited. Most of the studies have shown that the virus strains from drug naive patients do not show significant level of drug resistance mutations. The few immunological studies in Indian patients show that the Indian HIV infected patients show both HIV-specific CTL responses as well as neutralizing antibody response. Mapping of CTL epitopes showed that while Indian patients identify same regions of Gag antigen as recognized by South African subtype C infected patients, some regions are uniquely recognized by Indian patients. There are very few studies on host genetic factors in India in context with HIV infection. However there are evidences reported of association of host genetic factors such as HLA types and haplotypes and HIV disease.

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 ...