Injection network drivers of HIV prevention service utilization among people who inject drugs: results of a community-based sociometric network cohort in New Delhi, India.

INTRODUCTION: Injection drug networks may influence their network members' health-seeking behaviours. Using data from a sociometric injecting partner network of people who inject drugs (PWID) in New Delhi, India, we assessed the role of injecting partner (alter) behaviours on individual engagement in HIV prevention services. METHODS: We enumerated injecting partner linkages among 2512 PWID using coupon referrals and biometric data from November 2017 to March 2020. Participants completed interviewer-administered questionnaires and provided information on injection behaviours, injecting partners, HIV/hepatitis C (HCV) testing and service engagement. Multilevel multiple-membership models (MMMM) evaluated individual PWID HIV testing, medication for opioid use disorder (MOUD) and syringe service engagement as a function of alter attributes, accounting for membership across multiple ego-networks. Logistic regression models assessed parallel associations among socially proximal injecting peers, defined as PWID ≤3 path length from ego. RESULTS: Median age was 26 years; 99% were male. PWID had median 2 injecting partners and 8 socially proximal peers; 14% reported HIV testing, 33% accessed MOUD and 13% used syringe services 6 months prior. In MMMM analyses, PWID with ≥1 versus 0 injecting partners who received HIV testing were significantly more likely to report HIV testing (adjusted odds ratio [aOR]: 2.27, 95% confidence interval [CI]: 1.68-3.16), MOUD (aOR: 1.99, 95% CI: 1.60-2.53) and syringe service use (aOR: 1.66, 95% CI: 1.21-2.39). We observed similar findings for individual MOUD and syringe service use. Having ≥1 versus 0 HIV-positive partners was associated with decreased HIV testing and MOUD but increased syringe service use (aOR: 1.54, 95% CI: 1.09-2.17). PWID with ≥1 versus 0 socially proximal peers who used non-sterile injection equipment reported increased HIV testing (aOR: 1.39, 95% CI: 1.01-1.92), MOUD (aOR: 1.40, 95% CI: 1.10-1.77) and syringe service use (aOR: 1.82, 95% CI: 1.23-2.68). CONCLUSIONS: We found differential associative relationships between individual HIV prevention service engagement and the health or risk behaviours of direct and indirect alters. Characterizing network exposure beyond direct injecting partnerships provided important context on possible mechanisms of behavioural influence. Findings could be leveraged to design peer-based interventions that promote network diffusion of health-seeking behaviours.

Network centrality and HIV prevention service use among people who inject drugs: Findings from a sociometric network cohort in New Delhi, India.

BACKGROUND AND AIMS: Network centrality, an indicator of an individual's importance and potential to drive behavioral change, is rarely used to select peer educators. Individual-level predictors of network centrality might be useful to identify people who inject drugs (PWID) for potential roles as peer navigators or change agents in network-based interventions in settings where sociometric data are unavailable. We assessed the relationship between network centrality and HIV prevention service engagement to determine whether centrally-positioned PWID share measurable commonalities. DESIGN: Observational study and survey using baseline data from a sociometric network cohort of PWID, enumerated using network software and biometric data (2017-2020). Network ties corresponded to direct injection partnerships in the prior month. SETTING: New Delhi, India. PARTICIPANTS: A total of 2512 PWID who were ≥18 years, provided written informed consent, and reported illicit injection drug use within the 24 months before study enrollment. MEASUREMENTS: Interviewer-administered questionnaires measured demographics and substance use behaviors. Central versus peripheral network position was categorized using betweenness centrality 75th%ile . Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95%CI) between network position and HIV testing, medication for opioid use disorder (MOUD), or syringe service use. Lasso models selected predictors of central network position among 20 covariates detailing demographic, biologic, and substance use information. Predictive accuracy was evaluated using model performance metrics. FINDINGS: Overall, median age was 26 years (interquartile range 22-34); 99% were male; 628 were classified as central. Compared with PWID at the periphery, central PWID were more likely to use MOUD (aOR: 1.59, 95%CI: 1.30-1.94) and syringe services (aOR: 2.91, 95%CI: 2.25, 3.76) in the prior six months. Findings for HIV testing were inconclusive (aOR: 1.30, 95%CI: 1.00-1.69). The lasso variable selector identified several predictors of network centrality: HIV and hepatitis C infection, number of PWID seen in the prior month, injecting heroin and buprenorphine (vs. heroin only) six months prior, sharing injection equipment six months prior, experiencing drug overdose in the past year, and moderate/severe depression (vs. none/mild). Average agreement between model-predicted vs. observed values was 0.75; area under the receiver operator curve was 0.69. CONCLUSIONS: In a socioeconomic network of people who inject drugs (PWID) in New Delhi, India, there are common characteristics among individuals based on their network position (central vs. peripheral) but individual-level predictors have only moderate predictive accuracy. Although central network members appear to be more likely to use HIV prevention services than peripheral network members, their potential as change agents may be limited by other factors that impede their ability to adopt or promote HIV prevention service use.

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.

Drug use stigma, antiretroviral therapy use, and HIV viral suppression in a community-based sample of people with HIV who inject drugs.

OBJECTIVE: To examine the association of drug use stigma with antiretroviral therapy (ART) use and HIV viral suppression among people with HIV who inject drugs in India. DESIGN: Cross-sectional biobehavioral survey. METHODS: Between August 2016 and May 2017, persons aged at least 18 years who reported injection drug use in the past 2 years were recruited via respondent-driven sampling (RDS) in 12 Indian cities (approximately 1000 per city). The analysis was restricted to participants with laboratory-confirmed HIV infection who self-reported a prior HIV diagnosis and were eligible for ART per concurrent national HIV treatment guidelines. Enacted and internalized drug use stigma were each measured by five to six-item subscales. The study outcomes were HIV viral suppression (<150 copies/ml) and self-reported past 30-day ART use. RDS-II weighted multivariable logistic regression with a city-level random-intercept was used to estimate adjusted odds ratios (aOR) and corresponding 95% confidence intervals (CIs). RESULTS: Among 971 ART-eligible participants previously diagnosed with HIV, 65.1% reported ART use and 56.1% were virally suppressed. Reporting any enacted stigma (vs. none) was associated with lower odds of ART use [aOR = 0.26 (95% CI = 0.15-0.44)] and viral suppression [aOR = 0.49 (95% CI = 0.31-0.78)]. High internalized stigma scores (>median vs. ≤median) were associated with lower odds of viral suppression among participants aged at least 35 years [aOR = 0.51 (95% CI = 0.27-0.97)] but not among participants aged less than 35 years [aOR = 1.22 (95% CI = 0.57-2.60)]. Similar associations were observed in analyses restricted to participants ever linked to HIV care. CONCLUSION: Drug use stigma may be a barrier to HIV viral suppression among people with HIV who inject drugs, thereby hindering efforts to achieve HIV control.

Role of direct and indirect social and spatial ties in the diffusion of HIV and HCV among people who inject drugs: a cross-sectional community-based network analysis in New Delhi, India.

Background: People who inject drugs (PWID) account for some of the most explosive human immunodeficiency virus (HIV) and hepatitis C virus (HCV) epidemics globally. While individual drivers of infection are well understood, less is known about network factors, with minimal data beyond direct ties. Methods: 2512 PWID in New Delhi, India were recruited in 2017-19 using a sociometric network design. Sampling was initiated with 10 indexes who recruited named injection partners (people who they injected with in the prior month). Each recruit then recruited their named injection partners following the same process with cross-network linkages established by biometric data. Participants responded to a survey, including information on injection venues, and provided a blood sample. Factors associated with HIV/HCV infection were identified using logistic regression. Results: The median age was 26; 99% were male. Baseline HIV prevalence was 37.0% and 46.8% were actively infected with HCV (HCV RNA positive). The odds of prevalent HIV and active HCV infection decreased with each additional degree of separation from an infected alter (HIV AOR: 0.87; HCV AOR: 0.90) and increased among those who injected at a specific venue (HIV AOR: 1.50; HCV AOR: 1.69) independent of individual-level factors (p<0.001). In addition, sociometric factors, for example, network distance to an infected alter, were statistically significant predictors even when considering immediate egocentric ties. Conclusions: These data demonstrate an extremely high burden of HIV and HCV infection and a highly interconnected injection and spatial network structure. Incorporating network and spatial data into the design/implementation of interventions may help interrupt transmission while improving efficiency. Funding: National Institute on Drug Abuse and the Johns Hopkins University Center for AIDS Research.

Understanding the social and spatial relationships that connect people is a key element to stop the spread of infectious diseases. These networks are particularly relevant to combat epidemics among populations that are hard to reach with public health interventions. Network-based approaches, for example, can help to stop HIV or hepatitis C from spreading amongst populations that use injectable drugs. Yet how social and geographic connections such as acquaintances, injection partners, or preferred drug use places impact the risk of infection is still poorly mapped out. To address this question, Clipman et al. focused on people who inject drugs in New Delhi, India, a population heavily impacted by HIV and hepatitis C. Over 2500 people were recruited, each participant inviting their injection partners to also take part. The volunteers answered survey questions, including where they used drugs, and provided a blood sample to be tested. The results showed that, even after adjusting for individual risk factors, where people used drugs and with whom affected their risk of becoming infected with HIV and hepatitis C. In terms of social ties, the likelihood of HIV and hepatitis C infection decreased by about 13% for each person separating a given individual from an infected person. However, geographical networks also had a major impact. Injecting at a popular location respectively increased the odds of HIV and hepatitis C infection by 50% and 69%. In fact, even if the participant was not using drugs at these specific places, having an injection partner who did was enough to increase the risk for disease: for each person separating an individual from the location, the likelihood of being infected with HIV and hepatitis C decreased by respectively 14% and 10%. The results by Clipman et al. highlight how the relationships between physical spaces and social networks contribute to the spread of dangerous diseases amongst people who inject drugs. Ultimately, this knowledge may help to shape better public health interventions that would take into account the importance of geographical locations.

Drug use stigma and its association with active hepatitis C virus infection and injection drug use behaviors among community-based people who inject drugs in India.

BACKGROUND: Although drug use stigma is globally pervasive, quantitative evidence of its role in hepatitis C virus (HCV) transmission is limited. We evaluated the psychometric properties of a drug use stigma scale and examined the association between drug use stigma and active HCV infection among a community-based sample of people who inject drugs (PWID) in India. METHODS: Between 8/2016 and 5/2017, a cross-sectional sample of PWID was recruited from 12 Indian cities (~1000/city) using respondent-driven sampling. Participants were ≥18 years old and reported injection drug use (IDU) in the past 2 years. Multivariable logistic regression with a random-intercept for each city was used to estimate adjusted odds ratios (aOR) of active HCV infection (RNA>30 IU/mL). Analyses incorporated RDS-II weights. RESULTS: Of 11,663 participants, 73.1% reported IDU in the past 6 months and 33.8% had active HCV infection. Exploratory factor analysis yielded a four-factor solution of enacted, vicarious, felt normative and internalized drug use stigma with high internal consistency (Cronbach's α: 0.85-0.92). In analyses adjusted for age, gender, northeast region, education, homelessness, incarceration, alcohol dependence, HIV status, frequency of IDU, and ever sharing needles/syringes, PWID reporting any enacted stigma had greater odds of active HCV infection (aOR = 1.27 [95% CI = 1.13-1.43]) as did PWID with internalized stigma scores in the highest quartile (vs. lowest quartile; aOR = 1.69 [95% CI = 1.11-2.56]). Among PWID who reported IDU in the past 6 months, multiple forms of stigma were associated with higher frequency of IDU, sharing needles/syringes, having multiple injection partners, and IDU in public spaces. CONCLUSION: Using a multidimensional drug use stigma scale, various forms of stigma were significantly associated with active HCV infection and injection drug use-related risk behaviors. Collectively, these data suggest that drug use stigma may play a role in HCV transmission and impede efforts to achieve HCV elimination. Strategies to diminish drug use stigma are warranted.

Temporal change in population-level prevalence of detectable HIV viraemia and its association with HIV incidence in key populations in India: a serial cross-sectional study.

BACKGROUND: Population-level prevalence of detectable HIV viraemia (PDV) has been proposed as a metric for monitoring the population-level effectiveness of HIV treatment as prevention. We aimed to characterise temporal changes in PDV in people who inject drugs (PWID) and men who have sex with men (MSM) in India and evaluate community-level and individual-level associations with cross-sectional HIV incidence. METHODS: We did a serial cross-sectional study in which baseline (from Oct 1, 2012, to Dec 19, 2013) and follow-up (from Aug 1, 2016, to May 28, 2017) respondent-driven sampling (RDS) surveys were done in MSM (ten community sites) and PWID (12 community sites) across 21 cities in India. Eligible participants were those aged 18 years or older who provided informed consent and possessed a valid RDS referral coupon. Annualised HIV incidence was estimated with validated multiple-assay algorithms. PDV was calculated as the percentage of people with detectable HIV RNA (>150 copies per mL) in a community site. Community-level associations were determined by linear regression. Multivariable, multilevel Poisson regression was used to assess associations with recent HIV infection. FINDINGS: We recruited 21 990 individuals in the baseline survey and 21 726 individuals in the follow-up survey. The median community-level HIV incidence estimate increased from 0·9% (range 0·0-2·2) at baseline to 1·5% (0·5-3·0) at follow-up in MSM and from 1·6% (0·5-12·4) to 3·6% (0·0-18·4) in PWID. At the community-level, every 1 percentage point increase in baseline PDV and temporal change in PDV between surveys was associated with higher annualised HIV incidence at follow-up: for baseline PDV ß=0·41 (95% CI 0·18-0·63) and for change in PDV ß=0·52 (0·38-0·66). After accounting for individual-level risk factors, every 10 percentage point increase in baseline PDV and temporal change in PDV was associated with higher individual-level risk of recent HIV infection at follow-up: adjusted risk ratio 1·85 (95% CI 1·44-2·37) for baseline PDV and 1·81 (1·43-2·29) for change in PDV. INTERPRETATION: PDV was temporally associated with community-level and individual-level HIV incidence. These data support scale-up of treatment as prevention programmes to reduce HIV incidence and the programmatic use of PDV to monitor community HIV risk potential. FUNDING: US National Institutes of Health, Elton John AIDS Foundation.

Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India.

BACKGROUND AND AIMS: Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations, such as people who inject drugs (PWID). APPROACH AND RESULTS: We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes. CONCLUSIONS: This study characterizes HCV phylodynamics among PWID in a low and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes.

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.

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.

Epidemiology of HIV and hepatitis C infection among women who inject drugs in Northeast India: a respondent-driven sampling study.

BACKGROUND AND AIMS: Despite extensive research on HIV and hepatitis C (HCV) among people who inject drugs (PWID), there remains a gap in knowledge on the burden among women who inject drugs and their unique contexts and risk factors. This analysis compares HIV and HCV prevalence in female and male PWID and estimates injection and sexual risk correlates of prevalent HIV and HCV infection among women in Northeast India. DESIGN: Cross-sectional sample accrued using respondent-driven sampling. SETTING: Seven cities in Northeast India, 2013. PARTICIPANTS: A total of 6457 adult PWID. MEASUREMENTS: Participants completed an interviewer-administered survey. HIV infection was diagnosed on-site and HCV antibody testing was performed on stored specimens. HIV and HCV prevalence estimates were stratified by gender. Among women, the association of risk correlates with HIV and HCV were estimated using multi-level logistic regression models. FINDINGS: A total of 796 (15.9%) of the PWID were women, of whom 52.9% [95% confidence interval (CI) = 49.3-56.5%] were HIV-infected and 22.3% (CI = 19.9-24.7%) were HCV-infected. HIV and HCV prevalence among men was 17.4% (CI = 16.9-24.7%) and 30.4% (CI = 31.2-32.0%), respectively. Among women, correlates of HIV were widowhood [adjusted odds ratio (aOR) versus currently married = 4.03, CI = 2.13-7.60] and a higher number of life-time sexual partners (aOR ≥8 versus none = 3.08, CI = 1.07-8.86). Correlates of HCV were longer injection duration (aOR per 10 years = 1.70, CI = 1.25-2.27), injecting only heroin and a combination of drugs (aOR versus pharmaceuticals only = 5.63, CI = 1.68-18.9 and aOR = 2.58, CI = 1.60-4.16, respectively), sharing needles/syringes (aOR = 2.46, CI = 1.29-4.56) and a larger PWID network (aOR ≥ 51 versus 1-5 = 4.17, CI = 2.43-7.17). CONCLUSIONS: Women who inject drugs in Northeast India have a high HIV prevalence, which was more than double their hepatitis C (HCV) prevalence, an opposite pattern than is observed typically among male PWID. HIV infection is associated with sexual risk factors while injection-related behaviors appear to drive HCV infection.

Serum Fibrosis Markers for the Diagnosis of Liver Disease Among People With Chronic Hepatitis C in Chennai, India.

Background. Access to hepatitis C virus (HCV) treatment is limited in low- and middle-income countries (LMICs). Noninvasive biomarkers, such as fibrosis 4 (FIB-4) and aminotransferase to platelet ratio index (APRI), are low-cost alternatives to staging liver disease and identifying treatment need in people with chronic HCV infection, but their accuracy has not been evaluated in LMICs. Methods. We tested the accuracy of FIB-4 and APRI at validated cutoffs (FIB-4 <1.45, >3.25; APRI <0.5, >1.5) in predicting severe liver stiffness by elastography among 281 persons chronically infected with HCV. Multivariable logistic and Cox regression were used to identify markers of improved prediction and mortality, respectively. Results. Sensitivity and specificity of FIB-4 and APRI for predicting severe stiffness were 62% and 87% and 61% and 83%, respectively. Fibrosis 4 and APRI were less accurate in excluding significant stiffness; however, performance of models significantly improved with γ-glutamyl transpeptidase (GGT) and body mass index (BMI) (area under receiver operating characteristic curve, 0.81; 95% confidence interval, .76-.87). Severe liver stiffness predicted via FIB-4 >3.25, APRI >1.5, and a modified FIB-4 that included GGT and BMI were significantly associated with increased mortality. Conclusions. Fibrosis 4 and APRI may be useful in identifying individuals with severe stiffness who need treatment and continued monitoring in LMICs. Exclusion of significant stiffness may be improved by including GGT and BMI to FIB-4 models.

Getting to 90: linkage to HIV care among men who have sex with men and people who inject drugs in India.

UNAIDS set an ambitious target of "90-90-90" by 2020. The first 90 being 90% of those HIV-infected will be diagnosed; the second 90 being 90% of those diagnosed will be linked to medical care and on antiretroviral therapy (ART). While there has been dramatic improvement in HIV testing and ART use, substantial losses continue to occur at linkage-to-care following HIV diagnosis. Data on linkage among men who have sex with men (MSM) and people who inject drugs (PWID) are sparse, despite a greater burden of HIV in these populations. This cross-sectional study was conducted in 27 sites across India. Participants were recruited using respondent-driven sampling and had to be ≥18 years and self-identify as male and report sex with a man in the prior year (MSM) or injection drug use in the prior 2 years (PWID). Analyses were restricted to HIV-infected persons aware of their status. Linkage was defined as ever visiting a doctor for management of HIV after diagnosis. We explored factors that discriminated between those linked and not linked to care using multi-level logistic regression and area under the receiver operating curves (AUC), focusing on modifiable factors. Of 1726 HIV-infected persons aware of their status, 80% were linked to care. Modifiable factors around the time of diagnosis that best discriminated linkage included receiving assistance with HIV medical care (odds ratio [OR]: 10.0, 95% confidence interval [CI]): 5.6-18.2), disclosure of HIV-positive status (OR: 2.8; 95% CI: 2.4-6.1) and receiving information and counseling on management of HIV (OR: 2.3; 95% CI: 1.1-4.6). The AUC for these three factors together was 0.85, higher than other combinations of factors. We identified three simple modifiable factors around the time of diagnosis that could facilitate linkage to care among MSM and PWID in low- and middle-income countries to achieve UNAIDS targets.

High HIV burden among people who inject drugs in 15 Indian cities.

BACKGROUND: Injecting drug use has historically been the principal driver of the HIV epidemic in the northeast states of India. However, recent data indicate growing numbers of people who inject drugs (PWIDs) in north and central Indian cities. METHODS: We conducted face-to-face surveys among PWIDs in seven northeast and eight north/central Indian cities using respondent-driven sampling. We used a rapid HIV-testing protocol to identify seropositive individuals and multiassay algorithm to identify those with recent infection. We used multilevel regression models that incorporated sampling weights and had random intercepts for site to assess risk factors for prevalent and incident (recent) HIV infection. RESULTS: We surveyed 14 481 PWIDs from 15 Indian cities between January and December 2013. Participants reported high rates of needle/syringe sharing. The median (site range) estimated HIV prevalence and incidence were 18.1% (5.9, 44.9) and 2.9 per 100 person-years (0, 12.4), respectively. HIV prevalence was higher in northeast sites, whereas HIV incidence was higher in north/central sites. The odds of prevalent HIV were over three-fold higher in women than in men. Other factors associated with HIV prevalence or incidence included duration since first injection, injection of pharmaceutical drugs, and needle/syringe sharing. CONCLUSIONS: The burden of HIV infection is high among PWIDs in India, and may be increasing in cities where injecting drug use is emerging. Women who inject drugs were at substantially higher risk for HIV than men - a situation that may be mediated by dual injection-related and sexual risks.

Burden of hepatitis C virus disease and access to hepatitis C virus services in people who inject drugs in India: a cross-sectional study.

BACKGROUND: 90% of individuals infected with hepatitis C virus (HCV) worldwide reside in resource-limited settings. We aimed to characterise the prevalence of HCV, HIV/HCV co-infection, and the HCV care continuum in people who inject drugs in India. METHODS: 14 481 people (including 31 seeds--individuals selected as the starting point for sampling because they were well connected in the drug using community) who inject drugs were sampled from 15 cities throughout India using respondent-driven sampling from Jan 2, 2013 to Dec 19, 2013. Data from seeds were excluded from all analyses. HCV prevalence was estimated by the presence of anti-HCV antibodies incorporating respondent-driven sampling weights. HCV care continuum outcomes were self-reported except for viral clearance in treatment-experienced participants. FINDINGS: The median age of participants was 30 years (IQR 24-36) and 13 608 (92·4%) of 14 449 were men (data were missing for some variables). Weighted HCV prevalence was 5777 (37·2%) of 14 447; HIV/HCV co-infection prevalence was 2085 (13·2%) of 14 435. Correlates of HCV infection included high lifetime injection frequency, HIV positivity, and a high prevalence of people with HIV RNA (more than 1000 copies per mL) in the community. Of the 5777 people who inject drugs that were HCV antibody positive, 440 (5·5%) were aware of their status, 225 (3·0%) had seen a doctor for their HCV, 79 (1·4%) had taken HCV treatment, and 18 (0·4%) had undetectable HCV RNA. Of 12 128 participants who had not previously been tested for HCV, 6138 (50·5%) did not get tested because they had not heard of HCV. In the 5777 people who were HCV antibody positive, 2086 (34·4%) reported harmful or hazardous alcohol use, of whom 1082 (50·4%) were dependent, and 3821 (65·3%) reported needle sharing. Awareness of HCV positive status was significantly associated with higher education, HIV testing history, awareness of HIV positive status, and higher community antiretroviral therapy coverage. INTERPRETATION: The high burden of HCV and HIV/HCV co-infection coupled with low-access to HCV services emphasises an urgent need to include resource-limited settings in the global HCV agenda. Although new treatments will become available worldwide in the near future, programmes to improve awareness and reduce disease progression and transmission need to be scaled up without further delay. Failure to do so could result in patterns of rising mortality, undermining advances in survival attributed to widespread HIV treatment. FUNDING: US National Institutes of Health.

Mortality among injection drug users in Chennai, India (2005-2008).

BACKGROUND: Injection drug users (IDUs) have estimated mortality rates over 10 times higher than the general population; much of this excess mortality is HIV-associated. Few mortality estimates among IDUs from developing countries, including India, exist. METHODS: IDUs (1158) were recruited in Chennai from April 2005 to May 2006; 293 were HIV positive. Information on deaths and causes was obtained through outreach workers and family/network members. Mortality rates and standardized mortality ratios were calculated; multivariate Poisson regression was used to identify predictors of mortality. RESULTS: We observed 85 deaths over 1998 person-years (p-y) of follow-up [mortality rate (MR) 4.25 per 100 p-y; 95% confidence interval (CI) = 3.41-5.23]. The overall standardized mortality ratio was 11.1; for HIV-positive IDUs, the standardized mortality ratio was 23.9. Mortality risk among HIV-positive IDUs (MR: 8.88 per 100 p-y) was nearly three times that of negative IDUs (MR: 3.03 per 100 p-y) and increased with declining immune status (CD4 cells > 350: 5.44 per 100 p-y vs. CD4 cells < or = 200: 34.5 per 100 p-y). This association persisted after adjustment for confounders. The leading causes of mortality in both HIV negative and positive IDUs were overdose (n = 22), AIDS (n = 14), tuberculosis (n = 8) and accident/trauma (n = 9). CONCLUSION: Substantial mortality was observed in this cohort with the highest rates among HIV-positive IDUs with CD4 counts of less than 350 cells/microl. Although, in these 2 years, non-AIDS deaths outnumbered 0002030-related deaths, the relative contribution of 0002030-associated mortality is likely to increase with advancing HIV disease progression. These data reinforce the need for interventions to reduce the harms associated with drug use and increase HAART access among IDUs in Chennai.