Network-based strategies to combat HCV: Examining social and spatial drivers of transmission among PWID in New Delhi.

People who inject drugs (PWID) account for some of the fastest-growing HCV epidemics globally. While individual risk factors for infection are understood, less is known about network and spatial factors critical for elimination strategies. Two thousand five hundred twelve PWID in New Delhi, India, were recruited (2017-19) through network referrals. Biometrics identified duplicates and cross-network linkages. Participants completed semi-annual surveys and blood tests for HCV antibodies and RNA. Poisson regression and network analyses identified predictors of incident HCV and compared network-based intervention approaches. Baseline HCV antibody prevalence was 65.1%, of whom 79.6% were HCV RNA-positive. We observed 92 HCV seroconversions over 382.25 person-years (incidence: 24.1 per 100 person-years). Of the 92 seroconverters, 67% (62) were directly connected to an RNA-positive participant, and all were within one degree of separation from an RNA-positive participant. Individual-level factors associated with seroconversion included age, sexual activity, and injection behaviours. After adjusting for individual-level factors, seroconversion was significantly associated with number of RNA-positive partners (adjusted incidence rate ratio [AIRR] = 1.30) and injecting at a particular venue (AIRR = 2.53). This association extended to indirect ties, with 17% reduced odds of seroconversion for each degree of separation from the venue (AIRR = 0.83). Network analyses comparing intervention strategies found that targeting venues identified more cases compared to a treat-a-friend approach. We observed a fast-growing HCV epidemic driven by viremia within individuals' immediate networks and indirect social and spatial ties, demonstrating the importance of achieving broad, sustained virologic response and rethinking network-based interventions to include venues.

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.

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.

Buprenorphine treatment receipt characteristics and retention among people who inject drugs at Integrated Care Centers in India.

BACKGROUND: India is facing overlapping opioid injection and HIV epidemics among people who inject drugs (PWID) in several cities. Integrated Care Centers (ICCs) provide single-venue HIV and substance use services to PWID. We evaluated PWID engagement in daily observed buprenorphine treatment at 7 ICCs to inform interventions. METHODS: We analyzed 1-year follow-up data for PWID initiating buprenorphine between 1 January - 31 December 2018, evaluating receipt frequency, treatment interruptions (no buprenorphine receipt for 60 consecutive days with subsequent re-engagement), and drop-out (no buprenorphine receipt for 60 consecutive days without re-engagement). Using descriptive statistics, we explored differences between ICCs in the opioid-endemic Northeast region and ICCs in the emerging opioid epidemic North/Central region. We used a multivariable logistic regression model to determine predictors of treatment drop-out by 6 months. RESULTS: 1312 PWID initiated buprenorphine (76% North/Central ICCs vs. 24% Northeast ICCs). 31% of PWID in North/Central, and 25% in Northeast ICCs experienced ≥ 1 treatment interruption in 1 year. Over 6 months, 48% of PWID in North/Central vs. 60% in Northeast ICCs received buprenorphine ≤ 2 times/week (p < 0.0001). A third of PWID in North/Central vs. half in Northeast ICCs experienced treatment drop-out by 6 months (p < 0.001). In the multivariable model, living in Northeast cities was associated with increased odds of drop-out while counseling receipt was associated with decreased odds. CONCLUSIONS: Retention among PWID initiating buprenorphine at ICCs was comparable to global reports. However, regional heterogeneity in retention, and low daily buprenorphine receipt suggest patient-centered interventions adapted to regional contexts are urgently needed.

Deep learning and social network analysis elucidate drivers of HIV transmission in a high-incidence cohort of people who inject drugs.

Globally, people who inject drugs (PWID) experience some of the fastest-growing HIV epidemics. Network-based approaches represent a powerful tool for understanding and combating these epidemics; however, detailed social network studies are limited and pose analytical challenges. We collected longitudinal social (injection partners) and spatial (injection venues) network information from 2512 PWID in New Delhi, India. We leveraged network analysis and graph neural networks (GNNs) to uncover factors associated with HIV transmission and identify optimal intervention delivery points. Longitudinal HIV incidence was 21.3 per 100 person-years. Overlapping community detection using GNNs revealed seven communities, with HIV incidence concentrated within one community. The injection venue most strongly associated with incidence was found to overlap six of the seven communities, suggesting that an intervention deployed at this one location could reach the majority of the sample. These findings highlight the utility of network analysis and deep learning in HIV program design.

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.

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.

Voucher incentives improve linkage to and retention in care among HIV-infected drug users in Chennai, India.

BACKGROUND: Drug users (DUs), a population that accounts for some of the fastest-growing human immunodeficiency virus (HIV) epidemics globally, lag behind other populations with regard to HIV-related outcomes. We evaluated the role of voucher incentives on linkage and retention in care among DUs in India. METHODS: In this randomized clinical trial, 120 DUs who were aged ≥18 years, HIV-infected, antiretroviral therapy (ART) naive, and ART eligible and who reported drug use in the prior month were randomized to incentive (INC) or control (CTL) conditions for 12 months. Participants randomized to the INC arm received incentives (redeemable for food/household goods) ranging in value from USD4 to USD8 for achieving prespecified targets (eg, ART initiation, visits to ART center). Subjects in the CTL group could win vouchers in prize-bowl drawings, but HIV care behaviors were not incentivized. The primary endpoint was time to ART initiation. RESULTS: Sixty participants each were randomized to the INC and CTL arms between December 2009 and September 2010. Participants in the INC arm were more likely to visit the government ART center (49 vs 33; P = .002); 27 participants in the INC and 16 participants in the CTL arm initiated ART (P = .04; hazard ratio for ART = 2.33 [95% confidence interval, 1.15-4.73]). Participants in the INC arm also had significantly more visits to the ART center (median number of visits, 8 vs 3.5; P = .005). However, no difference in viral suppression was observed. CONCLUSIONS: Modest voucher incentives improved linkage to and retention in HIV care, but did not significantly impact viral suppression among DUs in India, a disenfranchised and difficult-to-treat population. CLINICAL TRIALS REGISTRATION: NCT01031745.

Factors associated with injection cessation, relapse and initiation in a community-based cohort of injection drug users in Chennai, India.

AIMS: To characterize factors associated with injection cessation, relapse and initiation. DESIGN: The Madras Injection Drug User and AIDS Cohort Study (MIDACS) is a prospective cohort of injection drug users (IDUs) recruited in 2005-06 with semi-annual follow-up to 2009. Discrete-time survival models were used to characterize predictors of time to first injection cessation and relapse. SETTING: Chennai, India. PARTICIPANTS: A total of 855 IDUs who reported injecting in the 6 months prior to baseline and had >1 follow-up visit. MEASUREMENTS: Cessation was defined as the first visit where no injection drug use was reported (prior 6 months) and relapse as the first visit where drug injection (prior 6 months) was reported after first cessation. FINDINGS: All participants were male; median age was 35 years. Over 3 years, 92.7% reported cessation [incidence rate (IR): 117 per 100 person-years]. Factors associated positively with cessation included daily injection and incarceration and factors associated negatively with cessation included marriage, alcohol and homelessness. Of those who reported cessation, 23.6% relapsed (IR: 19.7 per 100 person-years). Factors associated positively with relapse included any education, injection in the month prior to baseline, sex with a casual partner, non-injection drug use, incarceration and homelessness. Alcohol was associated negatively with relapse. The primary reasons for cessation were medical conditions (37%) and family pressure (22%). The majority initiated with non-injection drugs, transitioning to injection after a median 4 years. CONCLUSIONS: Injection drug users in southern India demonstrate a high rate of injection cessation over 3 years, but relapse is not uncommon. Compensatory increases in alcohol use indicate that cessation of injection does not mean cessation of all substance use. Family pressure, concerns about general health, fear of human immunodeficiency virus infection and a history of non-injection drug use are important correlates of cessation.

The relationship between social network factors, HIV, and Hepatitis C among injection drug users in Chennai, India.

OBJECTIVE: The purpose of this study was to examine whether social network factors predict HIV and Hepatitis C (HCV) serostatus after controlling for individual-level factors at baseline among a cohort of male injection drug users in Chennai, India. METHODS: The sample, which was recruited through street outreach, consists of 1078 males who reported having injected drugs in the last 6 months. RESULTS: The participants reported 3936 social support and risk network members. HIV and HCV positive serostatus were negatively associated with network member providing emotional support, and positively associated with network member providing material support. In addition, HCV positivity was associated with network member being an active drug user known for more than 10 years and network member being male kin networks, even after adjusting for individual demographic factors and risk behaviors. CONCLUSIONS: These findings suggest that social network factors are significantly linked to HIV and HCV status among IDUs in Southern India and highlight the mixed effects of social capital on health. Future HIV/HCV prevention efforts should incorporate IDU peers to alter drug network injection risk norms. For drug users who have minimal network support, support groups and other informal and formal support mechanisms may be need to help them with health care and psychological support needs for dealing with HIV/HCV.

Low incidences of human immunodeficiency virus and hepatitis C virus infection and declining risk behaviors in a cohort of injection drug users in Chennai, India.

The authors characterized human immunodeficiency virus (HIV) and hepatitis C virus (HCV) incidence and prospective changes in self-reported risk behavior over 2 years among 1,158 injection drug users (IDUs) recruited in Chennai, India, in 2005-2006. At baseline, HIV prevalence was 25.3%, and HCV prevalence was 54.5%. Seropositive persons with prevalent HIV infection were used to estimate baseline HIV incidence by means of the Calypte HIV-1 BED Incidence EIA (Calypte Biomedical Corporation, Portland, Oregon). Longitudinal HIV and HCV incidence were measured among 865 HIV-negative IDUs and 519 HCV antibody-negative IDUs followed semiannually for 2 years. Participants received pre- and posttest risk reduction counseling at each visit. Estimated HIV incidence at baseline was 2.95 per 100 person-years (95% confidence interval (CI): 1.21, 4.69) by BED assay; observed HIV incidence over 1,262 person-years was 0.48 per 100 person-years (95% CI: 0.17, 1.03). HCV incidence over 645 person-years was 1.71 per 100 person-years (95% CI: 0.85, 3.03). Self-reported risk behaviors declined significantly over time, from 100% of participants reporting drug injection at baseline to 11% at 24 months. In this cohort with high HIV and HCV prevalence at enrollment, the authors observed low incidence and declining self-reported risk behavior over time. While no formal intervention was administered, these findings highlight the potential impact of voluntary counseling and testing in a high-risk cohort.