Voucher incentives to improve viral suppression among HIV-positive people who inject drugs and men who have sex with men in India: a cluster randomised trial.

BACKGROUND: Progress on HIV treatment outcomes for people who inject drugs and men who have sex with men in India has been slow compared with that in other populations. We assessed whether HIV treatment incentives would improve outcomes among these groups. METHODS: We did a matched-pair, cluster randomised trial in 16 sites (eight for people who inject drugs and eight for men who have sex with men) across 15 cities in India. We recruited cohorts of HIV-positive people who inject drugs or men who have sex with men who were antiretroviral therapy (ART)-naive or had less than 12 months of ART exposure. We randomised sites to provide incentives or usual care. At intervention sites, we provided incentive vouchers, which could be exchanged for food or household goods, for attending motivational interviewing sessions and timely appointments at government ART clinics. An ART-naive participant meeting all targets could earn the equivalent to 14 days' wages over 12 months. The primary outcome was survival with viral suppression at 12 months. We used an intention-to-treat analytic approach appropriate for matched-pair cluster randomised trials, adjusting for baseline viral suppression. This study was registered with ClinicalTrials.gov, NCT02969915, and is complete. FINDINGS: Between Oct 30, 2017, and Oct 12, 2018, we recruited 1200 people who inject drugs and 1114 men who have sex with men living with HIV. Among people who inject drugs, 154 (12·8%) identified as female gender and 1046 (87·2%) as male. The site median percentage of participants earning one or more incentives was 96·1% (IQR 93·7-98·1). At 12 months, HIV viral suppression was 31·9% (n=383) among people who inject drugs and 52·1% (n=580) among men who have sex with men. The incentive intervention was not associated with significantly improved survival with viral suppression compared with usual care (adjusted prevalence difference 9·6 percentage points, 95% CI -4·4 to 23·7). INTERPRETATION: Despite high intervention engagement, incentives did not improve survival with viral suppression among people who inject drugs and men who have sex with men living with HIV in India. The poor outcomes overall underscore the need for innovative, multilevel approaches to engage marginalised people living with HIV in low-income and middle-income settings. FUNDING: US National Institutes of Health, Elton John AIDS Foundation.

Cumulative violence exposures among men who have sex with men living with HIV in India: Psychosocial correlates of HIV care continuum outcomes.

Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.

Respondent-driven sampling is more efficient than facility-based strategies at identifying undiagnosed people who inject drugs living with HIV in India.

INTRODUCTION: Injection drug use drives HIV epidemics in many low-resource settings, yet many people who inject drugs (PWID) living with HIV are not diagnosed. We assessed the ability of respondent-driven sampling (RDS) - which uses peer network connections - to identify undiagnosed PWID living with HIV compared to a facility-based strategy in India. METHODS: In six Indian cities from 2014 to 2017, integrated care centers (ICCs) provided HIV testing. From 2016 to 2017, RDS samples of PWID in these same cities were conducted. Using biometric matching, characteristics associated with identification by RDS only and both RDS and ICC, compared to ICC only were explored. Undiagnosed individuals tested positive and did not report a prior diagnosis. The number needed to recruit (NNR) (average number recruited to find one undiagnosed PWID living with HIV) and the identification rate (average number undiagnosed PWID identified per week) assessed the efficiency of RDS vs. ICCs. RESULTS: There were 10,759 ICC clients and 6012 RDS participants; 40% of RDS participants were also ICC clients resulting in 14,397 unduplicated PWID. PWID identified by RDS vs. ICC only were more likely to be male (adjusted odds ratios [aOR] RDS only: 6.8, both: 2.7) and living with HIV but undiagnosed (aOR RDS only: 2.5, both: 1.5). Overall, the RDS NNR was 11 and the ICC NNR was 26. The RDS identification rate (18.6/week) was faster than the ICC identification rate (2.7/week) overall and in all cities. CONCLUSIONS: RDS required screening fewer PWID and more rapidly identified undiagnosed PWID living with HIV as compared to ICCs.

Integration of a geospatially targeted community-based testing approach with respondent-driven sampling to identify people who inject drugs living with HIV and HCV in Patti and Gorakhpur, India.

BACKGROUND: Respondent-driven sampling (RDS), a network recruitment approach, is effective at reaching people who inject drugs (PWID), but other strategies may be needed to reach PWID at risk or living with HIV and/or Hepatitis C (HCV). We examined the impact of integrating geospatially targeted community-based HIV/HCV testing with an RDS survey. METHODS: PWID were recruited between 2019 and 2021 in Patti and Gorakhpur, India, in a two-phased approach for identifying PWID living with HIV/HCV. Phase 1 was an RDS survey, in which participants reported injection venues. Venues with the highest prevalence of HIV/HCV viremia were selected for Phase 2: community-based testing. All participants underwent rapid HIV and HCV testing and viral load quantification. Using Pearson's chi-squared test, two-sided exact significance tests, and t-tests, we compared prevalence and identification rates for each of the primary outcomes: the number of PWID 1) living with HIV/HCV, 2) undiagnosed, and 3) viremic. RESULTS: Both approaches identified large numbers of PWID (n∼500 each; N=2011) who were living with HIV/HCV and had transmission potential (i.e., detectable viremia). The community-based approach identified a higher proportion of individuals living with HCV (76.4% vs. 69.6% in Gorakhpur and 36.3% vs. 29.0% in Patti). Community-based testing was also faster at identifying PWID with detectable HIV viremia. Both approaches identified PWID with varying demographic characteristics. CONCLUSIONS: Community-based testing was more efficient than RDS overall, but both may be required to reach PWID of varying characteristics. Surveillance should collect data on injection venues to facilitate community-based testing and maximize case identification.

Antiretroviral Drug Resistance in HIV Sequences From People Who Inject Drugs and Men Who Have Sex With Men Across 21 Cities in India.

Background: Drug resistance testing is limited in public-sector human immunodeficiency virus (HIV) care in India, and there are few systematic samplings for prevalent drug resistance mutations (DRMs), particularly among men who have sex with men (MSM) and people who inject drugs (PWID). Methods: We conducted genotypic resistance testing on 915 HIV sequences sampled from viremic self-reported antiretroviral therapy (ART) experienced and naive PWID and MSM recruited from 21 cities across India in 2016-2017. We analyzed factors associated with resistance using logistic regression and evaluated evidence for transmitted resistance using phylogenetic analyses. Results: Of the 915 participants sequenced, median age was 31, 436 were MSM, and 191 were ART experienced. Overall, 62.8% of ART-experienced participants and 14.4% of ART-naive participants were found to have low-level resistance or higher to 1 or more classes of drugs. Prevalence of tenofovir disoproxil fumarate resistance was 25.7% in ART-experienced participants and 1.11% in ART-naive participants. The highest proportion of drug resistance was seen across nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, and resistance was significantly more common among MSM participants than PWID. Phylogenetic analyses revealed that 54.6% of ART-naive participants with resistance who clustered had shared DRMs, suggesting transmitted resistance may have occurred. Conclusions: Patients experiencing virologic failure on first-line therapy switched blindly to tenofovir/lamivudine/dolutegravir may effectively be receiving dolutegravir monotherapy due to resistance to tenofovir and lamivudine. While dolutegravir is expected to have full activity in the majority of patients in India, follow-up is needed to understand how resistance may affect long-term outcomes.

Impact of the COVID-19 pandemic on HIV prevention and care services among key populations across 15 cities in India: a longitudinal assessment of clinic-based data.

INTRODUCTION: The COVID-19 pandemic has threatened to diminish gains in HIV epidemic control and impacts are likely most profound among key populations in resource-limited settings. We aimed to understand the pandemic's impact on HIV-related service utilization among men who have sex with men (MSM) and people who inject drugs (PWID) across India. METHODS: Beginning in 2013, we established integrated care centres (ICCs) which provide HIV preventive and treatment services to MSM and PWID across 15 Indian sites. We examined utilization patterns for an 18-month period covering 2 months preceding the pandemic (January-February 2020) and over the first and second COVID-19 waves in India (March 2020-June 2021). We assessed: (1) unique clients accessing any ICC service, (2) ICC services provided, (3) unique clients tested for HIV and (4) HIV diagnoses and test positivity. Among an established cohort of PWID/MSM living with HIV (PLHIV), we administered a survey on the pandemic's impact on HIV care and treatment (June-August 2020). RESULTS: Overall, 13,854 unique clients visited an ICC from January 2020 to June 2021. In January/February 2020, the average monthly number of clients was 3761. Compared to pre-pandemic levels, the number of clients receiving services declined sharply in March 2020, dropping to 25% of pre-pandemic levels in April/May 2020 (first wave), followed by a slow rebound until April/May 2021 (second wave), when there was a 57% decline. HIV testing followed a similar trajectory. HIV test positivity changed over time, declining in the first wave and reaching its nadir around July 2020 at ∼50% of pre-pandemic levels. Positivity then increased steadily, eventually becoming higher than pre-pandemic periods. The second wave was associated with a decline in positivity for MSM but was relatively unchanged for PWID. Among 1650 PLHIV surveyed, 52% of PWID and 45% of MSM reported the pandemic impacted their ability to see an HIV provider. MSM had barriers accessing sexually transmitted infection testing and partner HIV testing. CONCLUSIONS: The COVID-19 pandemic led to significant decreases in HIV-related service utilization among key populations in India. This presents an opportunity for increased transmission and patients presenting with advanced disease among groups already disproportionately impacted by HIV.

Optimizing respondent-driven sampling to find undiagnosed HIV-infected people who inject drugs.

OBJECTIVE: We evaluated whether identification of undiagnosed HIV-infected people who inject drugs (PWID) via respondent-driven sampling (RDS) can be enhanced through a precision RDS (pRDS) approach. DESIGN/METHODS: First, using prior RDS data from PWID in India, we built a prediction algorithm for recruiting undiagnosed HIV-infected PWID. pRDS was tested in Morinda, Punjab where participants were randomly assigned to standard or pRDS. In the standard RDS approach, all participants received two recruitment coupons. For pRDS, the algorithm determined an individual's probability of recruiting an undiagnosed PWID, and individuals received either two (low probability) or five (high probability) coupons. Efficiency in identifying undiagnosed HIV-infected PWID for the RDS approaches was evaluated in two ways: the number needed to recruit (NNR) and identification rate/week. RESULTS: Predictors of recruiting undiagnosed PWID included HIV/HCV infection, network size, syringe services utilization, and injection environment. 1631 PWID were recruited in Morinda. From the standard RDS approach, 615 were recruited, including 39 undiagnosed; from pRDS, 1012 were recruited, including 77 undiagnosed. In pRDS, those with higher predicted probability were more likely to recruit others with HIV/HCV co-infection, undiagnosed and viremic HIV, and who utilized services. pRDS had a significantly higher identification rate of undiagnosed PWID (1.5/week) compared with the standard (0.8/week). The NNR for pRDS (13.1) was not significantly lower than the standard approach (15.8). CONCLUSION: pRDS identified twice as many undiagnosed and viremic PWID significantly faster than the standard approach. Leveraging RDS or similar network-based strategies should be considered alongside other strategies to ensure meeting UNAIDS targets.

Psychosocial Barriers to Viral Suppression in a Community-based Sample of Human Immunodeficiency Virus-infected Men Who Have Sex With Men and People Who Inject Drugs in India.

BACKGROUND: Little is known about the impact of psychosocial factors and substance use on viral suppression among human immunodeficiency virus (HIV)-infected key populations in resource-limited settings. Accordingly, we examined the association and interactions between depression, alcohol use, and recreational drug use on viral suppression among men who have sex with men (MSM) and people who inject drugs (PWID) in India. METHODS: MSM and PWID were recruited across India using respondent-driven sampling (RDS). Correlates of viral suppression were determined using Poisson regression models incorporating RDS-II weights. Two-way multiplicative interactions were assessed with separate models of all combinations of the 3 variables of interest using interaction terms; 3-way interactions were evaluated by stratifying 2-way interactions by the third variable. RESULTS: Among 1454 treatment-eligible HIV-infected MSM and 1939 PWID, older age (adjusted prevalence ratio [aPR], 1.14 for MSM; 1.41 for PWID) and higher HIV treatment literacy (aPR, 1.58 for MSM; 3.04 for PWID) were positively associated with viral suppression. Among MSM, there was evidence of a synergistic negative association between severe depression and recreational drug use (aPR, 0.37 [95% confidence interval {CI}, .16-.84]), alcohol dependence and recreational drug use (aPR, 0.45 [95% CI, .20-.99]), and severe depression, alcohol dependence, and recreational drug use (aPR, 0.23 [95% CI, .09-.57]). Among PWID, daily injection (aPR, 0.51 [95% CI, .31-.82]) was the primary barrier to suppression. CONCLUSIONS: Incorporating psychosocial and harm-reduction services into differentiated care models targeting MSM and PWID in low-resource settings is critical to achieving the 90-90-90 HIV/AIDS targets.

Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial.

BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.

Young people who inject drugs in India have high HIV incidence and behavioural risk: a cross-sectional study.

INTRODUCTION: There are limited data on young people who inject drugs (PWID) from low- and middle-income countries where injection drug use remains a key driver of new HIV infections. India has a diverse injection drug use epidemic and estimates suggest that at least half of PWID are ≤30 years of age. We compared injection and sexual risk behaviours and HIV incidence between younger and older PWID and characterized uptake of HIV testing and harm reduction services to inform targeted HIV prevention efforts. METHODS: We analysed cross-sectional data from 14,381 PWID recruited from cities in the Northeast and North/Central regions of India in 2013 using respondent driven sampling (RDS). We compared "emerging-adult" (18 to 24 years, 26% of sample) and "young-adult" PWID (25 to 30 years, 30% of sample) to older PWID (>30 years, 44% of sample) using logistic regression to evaluate factors associated with three recent risk behaviours: needle-sharing, multiple sexual partners and unprotected sex. We estimated age-stratified cross-sectional HIV incidence using a validated multi-assay algorithm. RESULTS: Compared to older adults, emerging-adults in the Northeastern states were significantly more likely to share needles (males adjusted odds ratio [aOR] 1.82; females aOR 2.29, p < 0.01), have multiple sexual partners (males aOR 1.56; females aOR 3.75, p < 0.01), and engage in unprotected sex (males aOR 2.29, p < 0.01). In the North/Central states, young-adult males were significantly more likely to needle-share (aOR 1.23, p < 0.05) while emerging-adult males were significantly more likely to have multiple sexual partners (aOR 1.74, p < 0.05). In both regions, emerging-adults had the lowest HIV testing. Participation in harm reduction services was low across all age groups. Annual HIV incidence was higher in emerging- and young-adult PWID in the North/Central region: emerging-adults: 4.3% (95% confidence interval [CI] 3.0, 5.6); young-adults: 4.9% (95% CI 3.7, 6.2); older adults: 2.1% (95% CI 1.4, 2.8). CONCLUSIONS: Higher HIV incidence and engagement in risky behaviours among younger PWID compared to older PWID, coupled with low utilization of harm reduction services highlight the importance of targeting this population in HIV programming. Age-specific interventions focused on addressing the needs of young PWID are urgently needed to curb the HIV epidemic in this vulnerable population.

Integrated HIV testing, prevention, and treatment intervention for key populations in India: a cluster-randomised trial.

BACKGROUND: To achieve reductions in HIV incidence, we need strategies to engage key population at risk for HIV in low-income and middle-income countries. We evaluated the effectiveness of integrated care centres in India that provided single-venue HIV testing, prevention, and treatment services for people who inject drugs (PWID) and men who have sex with men (MSM). METHODS: We did baseline respondent-driven sampling surveys in 27 sites across India, and selected 22 of these (12 PWID and ten MSM) for a cluster randomised trial on the basis of high HIV prevalence and logistical considerations. We used stratified (by PWID and MSM), restricted randomisation to allocate sites to either the integrated care intervention or usual care (11 sites per group). We implemented integrated care centres in 11 cities (six PWID integrated care centres embedded within opioid agonist treatment centres and five MSM centres within government-sponsored health services), with a single integrated care centre per city in all but one city. After a 2-year intervention phase, we did respondent-driven sampling evaluation surveys of target population members who were aged 18 years or older at all sites. The primary outcome was self-reported HIV testing in the previous 12 months (recent testing), determined via the evaluation survey. We used a biometric identification system to estimate integrated care centre exposure (visited an integrated care centre at least once) among evaluation survey participants at intervention sites. This trial is registered with ClinicalTrials.gov, number NCT01686750. FINDINGS: Between Oct 1, 2012, and Dec 19, 2013, we recruited 11 993 PWID and 9997 MSM in the baseline survey and, between Aug, 1 2016, and May 27, 2017, surveyed 11 721 PWID and 10 005 MSM in the evaluation survey using respondent-driven sampling, across the 22 trial sites. During the intervention phase, integrated care centres provided HIV testing for 14 698 unique clients (7630 PWID and 7068 MSM. In the primary population-level analysis, recent HIV testing was 31% higher at integrated care centres than at usual care sites (adjusted prevalence ratio [PR] 1·31, 95% CI 0·95-1·81, p=0·09). Among survey participants at intervention sites, integrated care centre exposure was lower than expected (median exposure 40% at PWID sites and 24% at MSM sites). In intervention sites, survey participants who visited an integrated care centre were more likely to report recent HIV testing than were participants who had not (adjusted PR 3·46, 2·94-4·06). INTERPRETATION: Although integrated care centres increased HIV testing among visitors, our low exposure findings suggest that the scale-up of a single integrated care centre in most cities was insufficient to serve the large PWID and MSM populations. Future work should address the use of population size estimates to guide the dose of combination HIV interventions targeting key populations. FUNDING: US National Institutes of Health and the Elton John AIDS Foundation.

Is there synergy in syndemics? Psychosocial conditions and sexual risk among men who have sex with men in India.

Syndemic theory describes the clustering and synergistic interaction of disease driven by contextual and social factors, which worsen health outcomes for a population, and has been applied to men who have sex with men (MSM) and their risk for HIV and other sexually transmitted infections. Recent reviews, however, have critiqued prevailing approaches in syndemic studies that assess only additive associations without evaluation of synergy. Following these suggestions, we compared the traditional additive approach with a test for synergistic association of 5 syndemic conditions (alcohol dependence, illicit drug use, depression, intimate partner violence (IPV), and childhood sexual abuse (CSA)) with unprotected anal intercourse (UAI) and active syphilis infection among 11,771 MSM recruited through respondent driven sampling from 12 cities in India. UAI was assessed via self-report and active syphilis infection was diagnosed by RPR and THPA tests. An additive association was explored using a condition count (range 0-5), and synergy was tested using relative excess risk due to interactions (RERIs) calculated from all 2-way and common 3-way interactions between conditions in adjusted regression models. There was a significant dose response associated with the syndemic count and UAI, and a similar pattern for syphilis, though not statistically significant. RERIs showed synergy for only one pair of conditions for UAI and syphilis, respectively: IPV + depression and alcohol dependence + illicit drug use. In this study, we found an additive association between syndemic conditions and UAI with evidence of synergistic interaction between a pair of psychosocial conditions, and no significant additive association, but a synergistic interaction between another pair of psychosocial conditions for syphilis. Our results lend further support to a critical reassessment of syndemic analyses. Closer attention to the cumulative development, underlying causal pathways, and possible synergistic interaction of co-occurring epidemics through combined qualitative and quantitative methodologies may yield more effective interventions for vulnerable, marginalized populations.

HIV risks among women who are married to men who have sex with men in India: a qualitative investigation.

In countries such as India, men who have same-sex partnerships may marry women due to cultural pressures regardless of their sexual desires and preferences. The wives of such men may be at risk for HIV but limited existing research addresses this issue. This qualitative study used in-depth interviews to investigate HIV-related risk among married men who have sex with men (n = 34) and women who were aware of their husband's same-sex behaviour (n = 13) from six research sites in five states and a Union Territory in India: Delhi (Delhi), Visakhapatnam (Andhra Pradesh), Hyderabad (Telangana), Bengaluru (Karnataka), Chennai and Madurai (Tamil Nadu). Thematic analysis revealed that wives of men who have sex with men were at risk for HIV from their husbands' sexual practices, which are often hidden to avoid the potential consequences of stigmatisation, as well as from gender-based inequities that make husbands the primary decision-makers about sex and condom use, even when wives are aware of their husband's same-sex behaviour. Innovative interventions are needed to address HIV-related risk in couples where wives remain unaware of their husband's same-sex behaviour, and for wives who are aware but remain within these marriages.

Respondent-driven sampling for identification of HIV- and HCV-infected people who inject drugs and men who have sex with men in India: A cross-sectional, community-based analysis.

BACKGROUND: A major barrier to achieving ambitious targets for global control of HIV and hepatitis C virus (HCV) is low levels of awareness of infection among key populations such as men who have sex with men (MSM) and people who inject drugs (PWID). We explored the potential of a strategy routinely used for surveillance in these groups, respondent-driven sampling (RDS), to be used as an intervention to identify HIV- and HCV-infected PWID and MSM who are unaware of their status and those who are viremic across 26 Indian cities at various epidemic stages. METHODS AND FINDINGS: Data were collected as part of the baseline assessment of an ongoing cluster-randomized trial. RDS was used to accrue participants at 27 sites (15 PWID sites and 12 MSM sites) selected to reflect varying stages of the HIV epidemic among MSM and PWID in India. A total of 56 seeds recruited a sample of 26,447 persons (approximately 1,000 participants per site) between October 1, 2012, and December 19, 2013. Across MSM sites (n = 11,997), the median age was 25 years and the median number of lifetime male partners was 8. Across PWID sites (n = 14,450), 92.4% were male, the median age was 30 years, and 87.5% reported injection in the prior 6 months. RDS identified 4,051 HIV-infected persons, of whom 2,325 (57.4%) were unaware of their HIV infection and 2,816 (69.5%) were HIV viremic. It also identified 5,777 HCV-infected persons, of whom 5,337 (92.4%) were unaware that they were infected with HCV and 4,728 (81.8%) were viremic. In the overall sample (both MSM and PWID), the prevalence of HIV-infected persons who were unaware of their status increased with sampling depth, from 7.9% in participants recruited in waves 1 through 5 to 12.8% among those recruited in waves 26 and above (p-value for trend < 0.001). The overall detection rate of people unaware of their HIV infection was 0.5 persons per day, and the detection rate of HIV-infected persons with viremia (regardless of their awareness status) was 0.7 per day. The detection rate of HIV viremic individuals was positively associated with underlying HIV prevalence and the prevalence of HIV viremia (linear regression coefficient per 1-percentage-point increase in prevalence: 0.05 and 0.07, respectively). The median detection rate of PWID who were unaware of their HCV infection was 2.5 per day. The cost of identifying 1 unaware HIV-infected individual ranged from US$51 to US$2,072 across PWID sites and from US$189 to US$5,367 across MSM sites. The mean additional cost of identifying 1 unaware HCV-infected PWID was US$13 (site range: US$7-US$140). Limitations of the study include the exclusivity of study sites to India, lack of prior HIV/HCV diagnosis confirmation with clinic records, and lack of cost data from other case-finding approaches commonly used in India. CONCLUSIONS: In this study, RDS was able to rapidly identify at nominal cost a substantial number of unaware and viremic HIV-infected and HCV-infected individuals who were currently not being reached by existing programs and who were at high risk for transmission. Combining RDS (or other network-driven recruitment approaches) with strategies focused on linkage to care, particularly in high-burden settings, may be a viable option for achieving the 90-90-90 targets in key populations in resource-limited settings.

Injection Drug Network Characteristics Are Important Markers of HIV Risk Behavior and Lack of Viral Suppression.

BACKGROUND: People who inject drugs (PWID) who are highly connected within their injection drug networks may be important HIV transmission nodes if they frequently share syringes with other PWID and are not engaged in HIV care. In India, HIV transmission fueled by injection drug use is increasing; however, little is known about the associations between injection network size and syringe sharing and viral suppression. METHODS: We recruited 14,481 PWID between October 2012 and December 2013 by respondent-driven sampling across 15 sites in India. Interviewer-administered questionnaires assessed network characteristics, substance use, HIV testing experience, and access to health services. We used multilevel logistic regression modeling to evaluate the relationship between injection drug network size and (1) syringe sharing at last injection and (2) viral suppression among HIV-positive participants (<150 copies/mL). FINDINGS: The median injection network size was 3 (interquartile range: 1-5), and 7% of participants injected with >10 members in the past 30 days. PWID who had >10 members in their network were 1.65 times (95% confidence interval: 1.12 to 2.42, P = 0.0111) more likely to have shared a syringe at last injection compared with those in the 0-1 members in their drug networks. In addition, individuals with the largest injection drug networks were 31% (95% confidence interval: 0.53 to 0.90, P = 0.006) less likely to be virally suppressed compared with those in the smallest injection drug networks. DISCUSSION: Individuals with larger networks may be important in HIV transmission within injection drug networks because they were the most likely to engage in recent syringe sharing and least likely to be virally suppressed.

Gender Differences in Factors Related to HIV Risk Behaviors among People Who Inject Drugs in North-East India.

People who inject drugs (PWID) in India are at high risk for HIV, with women being at elevated risk. Using a socio-ecological framework, this study assessed whether factors associated with HIV transmission risk behaviors differed across men and women PWID. Data for this cross-sectional study were collected from 6449 PWID in 7 cities in Northeast India. Men (n = 5653) and women (n = 796) PWID were recruited using respondent-driven sampling (RDS). We assessed sex differences in two recent HIV transmission risk behaviors: multiple sex partners and needle/syringe sharing. We used multi-level logistic regression models, which incorporated sampling weights and random intercepts for city, to assess factors associated with these HIV risks, separately among men and women. The prevalence of HIV was significantly higher among women than men (53% vs 18.4%, p<0.01). Nearly 13% of men and 8% of women (p = .30) had multiple partners. Employment in men and relationship status and stigma in women were significantly associated with multiple partners. Approximately 25% of men and 19% of women engaged in needle sharing (p = .16). Younger age in women and depression symptoms in men were significantly associated with increased risk for sharing needles. We found that sexual and drug related risk behaviors were common among PWID in Northeast India, and there were differences between men and women in the socio-ecologic correlates of these behaviors. Contextually-integrated and gender-specific HIV prevention and intervention efforts are needed that consider factors at individual, interpersonal- and community-levels that uniquely impact HIV risks among PWID.

Design of the Indian NCA study (Indian national collaboration on AIDS): a cluster randomized trial to evaluate the effectiveness of integrated care centers to improve HIV outcomes among men who have sex with men and persons who inject drugs in India.

BACKGROUND: Globally, men who have sex with men and people who inject drugs remain disproportionately affected by HIV, but they have not been the focus of prevention and treatment interventions in many resource-limited settings. METHODS/DESIGN: This cluster-randomized trial (conducted from June 2012 to June 2017), evaluates whether single-venue, integrated delivery of core HIV services to vulnerable high-risk populations improves service utilization and consequently, HIV testing and other outcomes along the HIV care continuum. Core services include: HIV counseling and testing, information, education and communication, condom distribution, needle and syringe exchange programs, opioid agonist therapy, management of sexually transmitted infections, tuberculosis screening, diagnosis, and treatment, and antiretroviral therapy. Stratified restricted randomization was used to allocate 22 Indian cities (10 men who have sex with men and 12 people who inject drugs sites) at a 1:1 ratio to either the intervention or control condition. Integrated care centers were scaled-up and implemented in the 11 intervention cities and outcomes will be assessed by pre- and post-intervention surveys at intervention and control sites. As men who have sex with men and people who inject drugs are hidden populations, with no sampling frame, respondent-driven sampling will be used to accrue samples for the two independent cross-sectional surveys. DISCUSSION: For an AIDS-free generation to be realized, prevention, care and treatment services need to reach all populations at risk for HIV infection. There is a clear gap in access to services among men who have sex with men and people who inject drugs. Trials need to be designed to optimize utilization of services in these populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01686750 Date of Registration: September 13, 2012.

The prevalence and impact of childhood sexual abuse on HIV-risk behaviors among men who have sex with men (MSM) in India.

BACKGROUND: Childhood sexual abuse (CSA) is a significant global public health problem, which is associated with negative psychosocial outcomes and high-risk sexual behaviors in adults. Men who have sex with men (MSM) often report higher prevalence of CSA history than the general population, and CSA may play a key role in MSM's greater vulnerability to HIV. METHODS: This study examined the prevalence of CSA history and its impact on the number of recent HIV-related risk behaviors (unprotected anal intercourse, high number of male and female sexual partners, alcohol use, drug use, and sex work in prior 6 months) and lifetime risk behaviors and experiences (high number of lifetime male and female sexual partners, early sexual debut, injection drug use, sex work, and intimate partner violence) among 11,788 adult MSM recruited via respondent driven sampling across 12 sites in India, with additional insights from thematic analysis of qualitative research with 363 MSM from 15 sites. RESULTS: Nearly a quarter (22.4 %) of participants experienced CSA, with substantially higher prevalence of CSA in the South and among kothis (feminine sexual identity). Qualitative findings revealed that older, trusted men may target young and, especially, gender nonconforming boys, and perpetrators' social position facilitates nondisclosure. CSA may also initiate further same-sex encounters, including sex work. In multivariable analysis, MSM who experienced CSA had 21 % higher rate of recent (adjusted rate ratio [aRR = 1.21], 95 % confidence interval [CI]: 1.14-1.28), and 2.0 times higher lifetime (aRR = 2.04, 95 % CI: 1.75-2.38) HIV-related behaviors/experiences compared with those who did not. CONCLUSION: This large, mixed-methods study found high overall prevalence of CSA among MSM (22.4 %), with substantially higher prevalence among MSM residing in the South and among more feminine sexual identities. Qualitative findings highlighted boys' vulnerabilities to CSA, especially gender nonconformity, and CSA's role in further sexual encounters, including sex work. Additionally, CSA was associated with an elevated rate of recent, and an even higher rate of lifetime HIV-related risk factors. Our results suggest an acute need for the development of CSA prevention interventions and the integration of mental health services for MSM with histories of CSA as part of HIV-prevention efforts.

Diverse Rates of Depression Among Men Who Have Sex with Men (MSM) Across India: Insights from a Multi-site Mixed Method Study.

Poor psychosocial health contributes to HIV risk behavior and reduced engagement in treatment and care. This study investigates depression and its correlates among 11,992 MSM recruited via respondent driven sampling in 12 cities across India using the Patient Health Questionnaire-9 and supplemented by analysis of qualitative research from 15 sites with 363 MSM. Overall prevalence of depression was 11 %, with substantial variation across sites and subgroups of MSM, and high prevalence of suicidal thoughts among depressed MSM. In multivariable analyses identification as a kothi (feminine sexual identity) [adjusted odds ratio (aOR) = 1.91], disclosure of being MSM to non-family (aOR = 1.7) and family (aOR = 2.4), disclosure of HIV-status (aOR = 5.6), and substance use were associated with significantly higher odds of depression. Qualitative results emphasized dire social consequences of disclosing MSM- and HIV-status, especially to family, including suicidality. Combination prevention interventions should include mental health services that address disclosure, suicidality, and substance use.

High HIV prevalence and incidence among MSM across 12 cities in India.

OBJECTIVE: To characterize prevalence, incidence, and associated correlates of HIV infection among MSM in 12 cities across India. DESIGN: Cross-sectional sample using respondent-driven sampling from September 2012 to June 2013. METHODS: A total 12022 MSM (~1000/city) were recruited. Participants had to be at least 18 years, self-identify as male, and report oral/anal intercourse with a man in the prior year. HIV infection was diagnosed using three rapid tests. Cross-sectional HIV incidence was estimated using a multiassay algorithm. All estimates incorporate respondent-driven sampling-II weights. RESULTS: Median age was 25 years, 45% self-identified as 'panthi' (predominantly penetrative anal intercourse) and 30.6% reported being married to a woman. Weighted HIV prevalence was 7.0% (range: 1.7-13.1%). In multivariate analysis, significantly higher odds of HIV infection was observed among those who were older, had lower educational attainment, were practicing purely receptive anal sex or both receptive and penetrative sex, and those who were herpes simplex virus-2 positive. Of 1147 MSM who tested HIV positive, 53 were identified as recent HIV infections (annualized incidence = 0.87%; range = 0-2.2%). In multivariate analysis, injecting drugs in the prior 6 months, syphilis, and higher number of male partners and fewer female partners were significantly associated with recent HIV infection. CONCLUSION: We observed a high burden of HIV among MSM in India with tremendous diversity in prevalence, incidence, and risk behaviors. In particular, we observed high incidence in areas with relatively low prevalence suggesting emerging epidemics in areas not previously recognized to have high HIV burden.