Ramesh Paranjape

Determinants of HIV prevalence among female sex workers in four south Indian states: analysis of cross-sectional surveys in twenty-three districts

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 ≤ 0.001] and for public place-based FSW (AOR 1.32, P = 0.005). Unmarried FSW and those who were widowed/divorced/separated, or from the devadasi tradition, had higher odds of being HIV positive (AOR 1.79, P ≤ 0.001 and 1.98, P < 0.001, respectively), than those currently married. The estimated district level variance in HIV prevalence was lowest (0.152) for brothel-based unmarried FSW, followed by brothel-based widowed/divorced/separated or devadasi FSW (0.192). Conclusion:Heterogeneity in the organization and structure of sex work is an important determinant of variations in HIV prevalence among FSW across districts in India, much more so than the districts themselves. This understanding should help to improve the design of HIV preventive interventions.

Sexual practices HIV and sexually transmitted infections among self-identified men who have sex with men in four high HIV prevalence states of India.

Objective:To describe the sociodemographic characteristics, prevalence of high-risk sexual behaviours, HIV, sexually transmitted infections (STI), and perception of risk in self-identified men who have sex with men (MSM) in four south Indian states. Methods:A cross-sectional probability-based survey of 4597 self-identified MSM in selected districts from four states in south India was undertaken. Self-defined sexual identity, sexual behaviour, and STI/HIV knowledge were assessed using a structured questionnaire. Blood and urine samples were tested for HIV and STI. Recruitment criteria differed slightly across states. Results:When grouped by self-identity, the HIV prevalence was: hijra (transgender) 18.1%; bisexuals 15.9%; kothis (anal-receptive) 13.5%; double-deckers (both anal-insertive/anal-receptive) 10.5%; and panthis (anal-insertive) 7.6%. Reported condom use with last paid male partner was over 80% in all states and categories. Consistent condom use was overall low among self-identified MSM, with less than 29% with non-commercial non-regular male partners and less than 49% with regular male partners. The percentage of self-identified MSM with regular female partners was 4–43% and with commercial female partners was 14–36% across states, and consistent condom use differed by self-identity. Syphilis prevalence was high among kothis and hijras (15.8 and 13.6%, respectively). Urethral gonorrhoea prevalence was less than 1% and chlamydia prevalence ranged from 0.4 to 4.0%. Conclusion:HIV prevalence and risk behaviour within these self-identified MSM communities in south India is high. Moreover, a significant proportion of them had female partners, both regular and commercial. The national programmes focus on HIV prevention services for these high-risk MSM is justified.

Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

Background Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. Methods and Findings We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. Conclusions Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Baseline integrated behavioural and biological assessment among most at-risk populations in six high-prevalence states of India: design and implementation challenges

Objective:This paper presents key methodological approaches and challenges in implementing and analysing the first round of the integrated biobehavioural assessment of most-at-risk populations, conducted in conjunction with evaluation of Avahan, the India AIDS initiative. Methods:The survey collected data on HIV risk behaviours, sexually transmitted infections and HIV prevalence in 29 districts in six high-prevalence states of India. Groups included female sex workers and clients, men who have sex with men, injecting drug users and truck drivers. Strategies for overcoming some challenges of the large-scale surveys among vulnerable populations, including sampling hidden populations, involvement of the communities targeted by the survey, laboratory and quality control in remote, non-clinic field settings, and data analysis and data use are presented. Discussion:Satisfying the need for protocols, guidelines and tools that allowed for sufficient standardization, while being tailored enough to fit diverse local situations on such a large scale, with so many implementing partners, emerged as a major management challenge. A major lesson from the first round is the vital importance of investing upfront time in tailoring the sampling methods, data collection instruments, and analysis plan to match measurement objectives. Conclusion:Despite the challenges, the integrated biobehavioural assessment was a huge achievement, and was largely successful in providing previously unavailable information about the HIV situation among populations that are critical to the curtailment of HIV spread in India. Lessons from the first round will be used to evolve the second round into an exercise with increased evaluative capability for Avahan.

Feasibility of pooling sera for HIV-1 viral RNA to diagnose acute primary HIV-1 infection and estimate HIV incidence.

ObjectiveTo develop a pooling method for detection of viral RNA for diagnosis of acute HIV infection and estimation of HIV-1 incidence. MethodsSera from 700 consecutive seronegative patients attending sexually transmitted disease clinics in Pune, India, were screened individually for p24 antigen, and pooled into seven pools of 100 for detection of HIV-1 RNA by reverse transcriptase-polymerase chain reaction. HIV-1 incidence was calculated by the traditional cohort method, the p24 antigen method, and a multistage pooling method in which RNA-positive pools were re-analyzed in smaller pools. ResultsSera from 700 individuals were grouped into seven pools of 100, of which four were positive. These four positive pools were subdivided into eight pools of 50, of which seven were positive. The seven positive pools were subdivided into 35 pools of 10, of which 10 were positive. Based on the 10 RNA-positive pools, the point estimate of HIV-1 incidence was 19.9% per year [95% confidence interval (CI), 7.3–31.8%]. Of the 700 samples analyzed for p24 antigen, eight were positive, resulting in a point estimate of incidence of 18.5%/year (8.0–36.5%). In contrast, the incidence rate based on the traditional cohort method of follow-up was lower at 9.4%/year (4.8–16.4%) due to a low follow-up rate. Testing of individual samples from the 10 RNA-positive pools identified 10 individuals with acute primary HIV-1. ConclusionThe multistage pooling method for detection of HIV-1 RNA was more sensitive than the p24 antigen method, and was five-fold less expensive than the p24 antigen assays. Pooling samples for RNA detection was effective in estimating current incidence rates with cost savings that would be practical for use in developing countries.

Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India

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. 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.

Injecting and sexual risk behaviours, sexually transmitted infections and HIV prevalence in injecting drug users in three states in India.

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 (<2%). HCV prevalence was more than 50% in Mumbai/Thane and Manipur. Conclusion:Irrespective of regional differences, high-risk behaviour of needle sharing and low condom use makes IDU a critical subpopulation for HIV prevention interventions. Interventions need to address the differing drug use patterns in the regions and transmission prevention among non-paid regular and casual female partners of IDU in the northeast districts and paid female partners in Mumbai/Thane.

Risk behaviour, sexually transmitted infections and HIV among long-distance truck drivers: a cross-sectional survey along national highways in India

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 Indias 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.

Sensitivity and specificity of rapid HIV testing of pregnant women in India

OBJECTIVE Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women. METHODS Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA). RESULTS Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests. CONCLUSION In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.

Assessment of the population-level effectiveness of the Avahan HIV-prevention programme in South India: a preplanned, causal-pathway-based modelling analysis

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 32700 HIV infections (95% credibility interval 17900-61600) 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 62800 (32000-118000) averted infections, and extrapolation suggested that 202000 (98300-407000) infections were averted across all 69 Avahan districts in South India, increasing to 606000 (290000-1 193000) 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.