Injection Partners Research Articles

Potential impact of curative and preventive interventions toward hepatitis C elimination in people who inject drugs–A network modeling study

BackgroundInjection-equipment-sharing networks play an important role in hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Direct-acting antiviral (DAA) treatments for HCV infection and interventions to prevent HCV transmission are critical components of an overall hepatitis C elimination strategy, but how they contribute to the elimination outcomes in different PWID network settings are unclear. MethodsWe developed an agent-based network model of HCV transmission through the sharing of injection equipment among PWID and parameterized and calibrated the model with rural PWID data in the United States. We modeled curative and preventive interventions at annual coverage levels of 12.5 %, 25 %, or 37.5 % (cumulative percentage of eligible individuals engaged), and two allocation approaches: random vs targeting PWID with more injection partners (hereafter ‘degree-based’). We compared the impact of these intervention strategies on prevalence and incidence of HCV infections. We conducted sensitivity analysis on key parameters governing the effects of curative and preventive interventions and PWID network characteristics. ResultsCombining curative and preventive interventions at 37.5 % annual coverage with degree-based allocation decreased prevalence and incidence of HCV infection by 67 % and 70 % over two years, respectively. Curative interventions decreased prevalence by six to 12 times more than preventive interventions, while curative and preventive interventions had comparable effectiveness on reducing incidence. Intervention impact increased with coverage almost linearly across all intervention strategies, and degree-based allocation was always more effective than random allocation, especially for preventive interventions. Results were sensitive to parameter values defining intervention effects and network mean degree. ConclusionDAA treatments are effective in reducing both prevalence and incidence of HCV infection in PWID, but preventive interventions play a significant role in reducing incidence when intervention coverage is low. Increasing coverage, including efforts in reaching individuals with the most injection partners, preventing reinfection, and improving compliance and retention in preventive services can substantially improve the outcomes. PWID network characteristics should be considered when designing hepatitis C elimination programs.

Comparison of a novel expanded social network recruitment intervention with risk network recruitment to HIV testing: locating undiagnosed cases in South Africa.

To ascertain whether a novel expanded social network recruitment to HIV testing (E-SNRHT) intervention recruits men and individuals with previously undiagnosed HIV at higher rates than risk network recruitment. Initial "seed" participants were prospectively randomly assigned to the E-SNRHT intervention or to risk network recruitment. Their network members were included in the study arm of their recruiter. Three Department of Health clinics and two drug treatment centers (DTCs) in the Msunduzi municipality of KwaZulu-Natal, South Africa. Clinics and DTCs referred 110 newly HIV-diagnosed adult "seeds" to the study from June 2022 to February 2023. E-SNRHT seeds were asked to recruit network members as described below; risk network recruitment arm seeds were asked to recruit recent sex and/or injection partners. Presenting a recruitment coupon (from clinic/DTC staff or another participant) was required for eligibility. E-SNRHT seeds were shown educational material about HIV transmission risks and then asked to recruit anyone they know (e.g., friends, family) whom they thought could benefit from HIV testing. Rates of recruiting men to HIV testing and locating individuals with previously undiagnosed HIV. E-SNRHT recruited significantly higher proportions of men to HIV testing (70.3 vs. 40.4%; χ2 = 16.33; P < 0.0005) and located significantly more previously undiagnosed cases of HIV per seed than risk network recruitment (rate ratio = 9.40; P < 0.0001). E-SNRHT also recruited significantly higher proportions of women with previously undiagnosed HIV (29.0 vs. 10.7%; χ2 = 3.87; P = 0.049). E-SNRHT is an important strategy to expand the reach of HIV testing among men and undiagnosed cases of HIV in KwaZulu-Natal.

Pilot Testing Two Versions of a Social Network Intervention to Increase HIV Testing and Case-finding among Men in South Africa's Generalized HIV Epidemic.

Locating undiagnosed HIV infections is important for limiting transmission. However, there is limited evidence about how best to do so. In South Africa, men have been particularly challenging to reach for HIV testing due, in part, to stigma. We pilot-tested two versions of a network-based case-finding and care-linkage intervention. The first, TRIP, asked "seeds" (original participants) to recruit their sexual and/or injection partners. The second, TRIPLE, aimed to circumvent some stigma-related issues by asking seeds to recruit anyone they know who might be at risk of being HIV-positive-unaware. We recruited 11 (18% male) newly diagnosed HIV-positive (NDP) seeds from two clinics in KwaZulu-Natal, South Africa and randomly assigned them to either TRIP or TRIPLE. Network members were recruited two steps from each seed. The TRIP arm recruited 12 network members; the TRIPLE arm recruited 62. Both arms recruited NDPs at higher rates than local clinic testing, with TRIP (50.0%) outperforming (p = 0.012) TRIPLE (14.5%). However, TRIPLE (53.2%) was far superior to clinics (27.8%) and to TRIP (25.0%) at recruiting men. Given challenges around testing and treating men for HIV in this context, these findings suggest that the TRIPLE expanded network-tracing approach should be tested formally among larger samples in multiple settings.

Distinctive model for HIV index testing (IT) in Eastern Europe: results of Ukraine’s physician-led, integrated IT programme

ObjectivesThe effectiveness of HIV index testing (IT) in Eastern Europe has not been described. This study reports the performance of a scaled IT programme in Ukraine.DesignThis observational study included clients...

Variation in HIV Transmission Behaviors Among People Who Use Drugs in Rural US Communities

People who use drugs (PWUD) continue to be at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within various rural communities is poorly understood. To examine the association of characteristics of rural PWUD with HIV transmission behaviors. In this cross-sectional study, surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin) were collected January 2018 through March 2020 and analyzed August through December 2022. A chain-referral sampling strategy identified convenience sample seeds who referred others who used drugs. Rural PWUD who reported any past 30-day injection drug use or noninjection opioid use "to get high" were included. Individual characteristics, including age, race, gender identity, sexual orientation, partnership status, drug of choice, and location, were collected. Past 30-day frequency of behaviors associated with HIV transmission, including drug injection, syringe sharing, opposite- and same-gender partners, transactional sex, and condomless sex, was assessed. Of 3048 rural PWUD (mean [SD] age, 36.1 [10.3] years; 225 American Indian [7.4%], 96 Black [3.2%], and 2576 White [84.5%] among 3045 with responses; and 1737 men [57.0%] among 3046 with responses), most participants were heterosexual (1771 individuals [86.8%] among 2040 with responses) and single (1974 individuals [68.6%] among 2879 with responses). Opioids and stimulants were reported as drug of choice by 1636 individuals (53.9%) and 1258 individuals (41.5%), respectively, among 3033 individuals with responses. Most participants reported recent injection (2587 of 3046 individuals [84.9%] with responses) and condomless sex (1406 of 1757 individuals [80.0%] with responses), among whom 904 of 1391 individuals (65.0%) with responses indicated that it occurred with people who inject drugs. Syringe sharing (1016 of 2433 individuals [41.8%] with responses) and transactional sex (230 of 1799 individuals [12.8%] with responses) were reported less frequently. All characteristics and behaviors, except the number of men partners reported by women, varied significantly across locations (eg, mean [SD] age ranged from 34.5 [10.0] years in Wisconsin to 39.7 [11.0] years in Illinois; P < .001). In multivariable modeling, younger age (adjusted odds ratio [aOR] for ages 15-33 vs ≥34 years, 1.36; 95% CI, 1.08-1.72) and being single (aOR, 1.37; 95% CI, 1.08-1.74) were associated with recent injection; younger age (aOR, 1.49; 95% CI, 1.20-1.85) and bisexual orientation (aOR vs heterosexual orientation, 2.27; 95% CI, 1.60-3.23) with syringe sharing; gender identity as a woman (aOR vs gender identity as a man, 1.46; 95% CI, 1.01-2.12), bisexual orientation (aOR vs heterosexual orientation, 2.59; 95% CI, 1.67-4.03), and being single (aOR, 1.71; 95% CI, 1.15-2.55) with transactional sex; and bisexual orientation (aOR vs heterosexual orientation, 1.60; 95% CI, 1.04-2.46) and stimulants as the drug of choice (aOR vs opioids, 1.45; 95 CI, 1.09-1.93) with condomless sex with someone who injects drugs. This study found that behaviors associated with HIV transmission were common and varied across communities. These findings suggest that interventions to reduce HIV risk among rural PWUD may need to be tailored to locally relevant factors.

Injection partnership characteristics and HCV status associations with syringe and equipment sharing among people who inject drugs

BackgroundSharing of syringes is the leading transmission pathway for hepatitis C (HCV) infections. The extent to which HCV can spread among people who inject drugs (PWID) is largely dependent on syringe-sharing network factors. Our study aims to better understand partnership characteristics and syringe and equipment sharing with those partners, including measures of relationship closeness, sexual activity, and social support, as well as self and partner HCV status to better inform interventions for young urban and suburban PWID.MethodsData are from baseline interviews of a longitudinal network-based study of young (aged 18–30) PWID (egos) and their injection network members (alters) in metropolitan Chicago (n = 276). All participants completed a computer-assisted interviewer-administered questionnaire and an egocentric network survey on injection, sexual, and support networks.ResultsCorrelates of syringe and ancillary equipment sharing were found to be similar. Sharing was more likely to occur in mixed-gender dyads. Participants were more likely to share syringes and equipment with injection partners who lived in the same household, who they saw every day, who they trusted, who they had an intimate relationship with that included condomless sex, and who provided personal support. PWID who had tested HCV negative within the past year were less likely to share syringes with an HCV positive partner compared to those who did not know their status.ConclusionPWID regulate their syringe and other injection equipment sharing to some extent by sharing preferentially with injection partners with whom they have a close personal or intimate relationship, and whose HCV status they are more likely to know. Our findings underscore the need for risk interventions and HCV treatment strategies to consider the social context of syringe and equipment sharing within partnerships.

Causes and risk factors of death among people who inject drugs in Indonesia, Ukraine and Vietnam: findings from HPTN 074 randomized trial

IntroductionThe HIV Prevention Trials Network (HPTN) 074 study demonstrated a positive effect of an integrated systems navigation and psychosocial counseling intervention on HIV treatment initiation, viral suppression, medication assisted treatment (MAT) enrollment, and risk of death among people who inject drugs (PWID). In this sub-study, we analyzed the incidence, causes, and predictors of death among HIV-infected and uninfected participants.MethodsThe HPTN 074 randomized clinical trial was conducted in Indonesia, Ukraine, and Vietnam. HIV-infected PWID with unsuppressed viral load (indexes) were recruited together with at least one of their HIV-negative injection partners. Indexes were randomized in a 1:3 ratio to the intervention or standard of care.ResultsThe trial enrolled 502 index and 806 partner participants. Overall, 13% (66/502) of indexes and 3% (19/806) of partners died during follow-up (crude mortality rates 10.4 [95% CI 8.1–13.3] and 2.1 [1.3–3.3], respectively). These mortality rates were for indexes nearly 30 times and for partners 6 times higher than expected in a population of the same country, age, and gender (standardized mortality ratios 30.7 [23.7–39.0] and 5.8 [3.5–9.1], respectively). HIV-related causes, including a recent CD4 < 200 cells/μL, accounted for 50% of deaths among indexes. Among partners, medical conditions were the most common cause of death (47%). In the multivariable Cox model, the mortality among indexes was associated with sex (male versus female aHR = 4.2 [1.5–17.9]), CD4 count (≥ 200 versus < 200 cells/μL aHR = 0.3 [0.2–0.5]), depression (moderate-to-severe versus no/mild aHR = 2.6 [1.2–5.0]) and study arm (intervention versus control aHR = 0.4 [0.2–0.9]). Among partners, the study arm of the index remained the only significant predictor (intervention versus control aHR = 0.2 [0.0–0.9]) while controlling for the effect of MAT (never versus ever receiving MAT aHR = 2.4 [0.9–7.4]).ConclusionsThe results confirm that both HIV-infected and uninfected PWID remain at a starkly elevated risk of death compared to general population. Mortality related to HIV and other causes can be significantly reduced by scaling-up ART and MAT. Access to these life-saving treatments can be effectively improved by flexible integrated interventions, such as the one developed and tested in HPTN 074.

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.

Network Correlates of Using a Syringe After an Injection Partner Among Women Who Inject Drugs in Philadelphia Pennsylvania.

This analysis aims to identify relationship-level correlates of receptive syringe sharing among women who inject drugs in Philadelphia. Sixty-four women who injected daily were recruited from Prevention Point Philadelphia's syringe exchange program (9/2/20 - 11/23/20). Interviewer-administered surveys collected (1) individual-level demographics and risk behaviors and (2) relationship-level information about each past-6-month injection partner and injecting practices between the two. We built two separate log-binomial regression models which accounted for clustering of network members within participants to identify relationship-level correlates of using a syringe after a partner. Women reported injecting with a syringe previously used by 21.14% of partners. Women were more likely to use a syringe after sex partners (Adjusted Prevalence Ratio [APR]model_1=2.77) and those who provided injection assistance (APRmodel_1=1.92) or emotional support (APRmodel_2=6.19). Future harm reduction efforts could train women to negotiate safer injection practices with sex partners and those who provide injection assistance and/or emotional support.

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.

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. 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>30IU/mL). Analyses incorporated RDS-II weights. 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. 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.

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.

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. 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. 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. 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. National Institute on Drug Abuse and the Johns Hopkins University Center for AIDS Research.

Engaging People Who Inject Drugs Living With HIV in Antiretroviral Treatment and Medication for Opioid Use Disorder: Extended Follow-up of HIV Prevention Trials Network (HPTN) 074.

BackgroundPeople who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention.MethodsParticipants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention.ResultsThe intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%).ConclusionsViral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention.

Phylogenetic Analysis of Human Immunodeficiency Virus from People Who Inject Drugs in Indonesia, Ukraine, and Vietnam: HPTN 074.

HIV Prevention Trials Network (HPTN) 074 evaluated human immunodeficiency virus (HIV) prevention interventions for people who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. Study interventions included support for HIV infection and substance use treatment. The study enrolled index participants living with HIV and injection partners who were not living with HIV. Seven partners acquired HIV infection during the study (seroconverters). We analyzed the phylogenetic relatedness between HIV strains in the cohort and the multiplicity of infection in seroconverters. Pol region consensus sequences were used for phylogenetic analysis. Data from next-generation sequencing (NGS, env region) were used to evaluate genetic linkage of HIV from the 7 seroconverters and the corresponding index participants (index-partner pairs), to analyze HIV from index participants in pol sequence clusters, and to analyze multiplicity of HIV infection. Phylogenetic analysis of pol sequences from 445 index participants and 7 seroconverters identified 18 sequence clusters (2 index-partner pairs, 1 partner-partner pair, and 15 index-only groups with 2-7 indexes/cluster). Analysis of NGS data confirmed linkage for the 2 index-partner pairs, the partner-partner pair, and 11 of the 15 index-index clusters. The remaining 5 seroconverters had infections that were not linked to the corresponding enrolled index participant. Three (42.9%) of the 7 seroconverters were infected with more than 1 HIV strain (3-8 strains per person). We identified complex patterns of HIV clustering and linkage among PWID in 3 communities. This should be considered when designing strategies for HIV prevention for PWID. NCT02935296.

Reported Participation Benefits in International HIV Prevention Research with People Who Inject Drugs.

Given ethical concerns about research involving people who inject drugs and those affected by HIV, identifying potential participation benefits is important. We evaluated participant-reported benefits in a trial conducted in Indonesia, Ukraine, and Vietnam that assessed an intervention combining psychosocial counseling and referral for antiretroviral therapy and substance use treatment for HIV-infected people who use drugs. Reported benefits were aggregated into three groups: clinical (antiretroviral therapy, reduced cravings, reduced drug use, lab testing, medical referral, mental health, physical health), social (employment, financial, relationships, reduced stigma), and general (gained knowledge, life improvement). Overall, 438 index participants (90.5%) and 642 injection partners (83.1%) reported at least one benefit. Significantly more index participants who received the study intervention reported at least one benefit versus those who received the standard of care. Clinical trial participation can provide broad direct and indirect benefits for stigmatized populations, which has implications for assessing the ethical appropriateness of studies with such populations.

Association of Self-Reported Abscess With High-Risk Injection-Related Behaviors Among Young Persons Who Inject Drugs.

Abscess is a common source of morbidity for people who inject drugs. We used data from the Study to Assess Hepatitis C Risk to measure prevalence of abscess and identify factors associated with the history of abscess. Of 541 participants, 388 (72%) were male and 149 (28%) were female. Almost half (n = 258, 48%) reported ever having an abscess. Persons who inject drugs with an abscess history were significantly more likely to have more injection partners (p = .01), inject heroin daily (p < .05), and share cookers (p = .001) and less likely to report using new syringes with each injection (p = .02). Most reported self-treating their last abscess and increasing drug use when having an abscess. High-risk injection-related activity was associated not only with infections such as HIV and hepatitis C virus but also with abscess. Nurses should screen patients presenting with abscess for high-risk practices and provide prevention education.

Hepatitis C transmission in young people who inject drugs: Insights using a dynamic model informed by state public health surveillance

Increasing injection of heroin and prescription opioids have led to increases in the incidence of hepatitis C virus (HCV) infections in US young adults since the early 2000s. How best to interrupt transmission and decrease HCV prevalence in young people who inject drugs (PWID) is uncertain.We developed an age-stratified ordinary differential equation HCV transmission model of PWID aged 15–64, which we fit to Michigan HCV surveillance data among young PWID aged 15–29. We used Latin hypercube sampling to fit to data under 10,000 plausible model parameterizations. We used the best-fitting 10% of simulations to predict the potential impact of primary (reducing injection initiation), secondary (increasing cessation, reducing injection partners, or reducing injection drug use relapse), and tertiary (HCV treatment) interventions (over the period 2017–2030) on acute and chronic HCV cases by the year 2030.Treating 3 per 100 current and former PWID per year could reduce chronic HCV by 27.3% (range: 18.7–30.3%) and acute HCV by 23.6% (range: 6.7–29.5%) by 2030 among PWID aged 15–29 if 90% are cured (i.e. achieved sustained virologic response [SVR] to treatment). Reducing the number of syringe sharing partners per year by 10% was predicted to reduce chronic HCV by 15.7% (range: 9.4–23.8%) and acute cases by 21.4% (range: 14.2–32.3%) among PWID aged 15–29 by 2030. In simulations of combinations of interventions, reducing injection initiation, syringe sharing, and relapse rates each by 10% while increasing cessation rates by 10% predicted a 27.7% (range: 18.0–39.7%) reduction in chronic HCV and a 38.4% (range: 28.3–53.3%) reduction in acute HCV.Our results highlight the need for HCV treatment among both current and former PWID and the scale up of both primary and secondary interventions to concurrently reduce HCV prevalence and incidence in Michigan.

Client and Provider Perspectives on Antiretroviral Treatment Uptake and Adherence Among People Who Inject Drugs in Indonesia, Ukraine and Vietnam: HPTN 074.

HIV-infected people who inject drugs (PWID) have low uptake of HIV services, increasing the risk of transmission to uninfected injection or sexual partners and the likelihood of AIDS-related deaths. HPTN 074 is a vanguard study assessing the feasibility of an integrated intervention to facilitate treatment as prevention to PWID in Indonesia, Ukraine, and Vietnam. We describe barriers to and facilitators of ART uptake and adherence among PWID. We conducted in-depth interviews with 62 participants, including 25 providers and 37 PWID at baseline across all sites. All interviews were recorded, transcribed, translated into English and coded in NVivo for analysis. Matrices were developed to identify emergent themes and patterns. Overall, differences between provider and PWID perspectives were greater than differences in cross-site perspectives. Providers and PWID recognized clinic access, financial barriers, side effects, and lack of information about HIV testing and ART enrollment as barriers to ART. However, providers tended to emphasize individual level barriers to ART, such as lack of motivation due to drug use, whereas PWID highlighted health systems barriers, such as clinic hours and financial burden, fears, and side effects. Providers did not mention stigma as a barrier though their language reflected stereotypes about drug users. The differences between provider and PWID perspectives suggest a gap in providers' understanding of PWID. This misunderstanding has implications for patient-provider interactions that may affect PWID willingness to access care or adhere to ART. Lessons learned from this study will be important as countries with a significant HIV burden among PWID design and implement programs to engage HIV-infected PWID in care and treatment.

Regional differences between people who inject drugs in an HIV prevention trial integrating treatment and prevention (HPTN 074): a baseline analysis.

IntroductionPeople who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention.MethodsWe present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two‐arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV‐positive index and their HIV‐negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours.ResultsThe majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self‐reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test – Alcohol Consumption Questions (AUDIT‐C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions.ConclusionsWhile regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations.

A scalable, integrated intervention to engage people who inject drugs in HIV care and medication-assisted treatment (HPTN 074): a randomised, controlled phase 3 feasibility and efficacy study

People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use. This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18-45 years (updated to 18-60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12-24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants. Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4-1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0-1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4-2·1; incidence rate difference -1·0 per 100 person-years, 95% CI -2·1 to 1·1). No severe adverse events due to the intervention were recorded. This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered. US National Institutes of Health.

Pockets of HIV Non-infection Within Highly-Infected Risk Networks in Athens, Greece.

As part of a network study of HIV infection among people who inject drugs (PWID) and their contacts, we discovered a connected subcomponent of 29 uninfected PWID. In the context of a just-declining large epidemic outbreak, this raised a question: What explains the existence of large pockets of uninfected people? Possible explanations include “firewall effects” (Friedman et al., 2000; Dombrowski et al., 2017) wherein the only HIV+ people that the uninfected take risks with have low viral loads; “bottleneck effects” wherein few network paths into the pocket of non-infection exist; low levels of risk behavior; and an impending outbreak. We considered each of these. Participants provided information on their enhanced sexual and injection networks and assisted us in recruiting network members. The largest connected component had 241 members. Data on risk behaviors in the last 6 months were collected at the individual level. Recent infection was determined by LAg (SediaTM Biosciences Corporation), data on recent seronegative tests, and viral load. HIV RNA was quantified using Artus HI Virus-1 RG RT-PCR (Qiagen). The 29 members of the connected subcomponent of uninfected participants were connected (network distance = 1) to 17 recently-infected and 24 long-term infected participants. Fourteen (48%) of these 29 uninfected were classified as “extremely high risk” because they self-reported syringe sharing and had at least one injection partner with viral load >100,000 copies/mL who also reported syringe sharing. Seventeen of the 29 uninfected were re-interviewed after 6 months, but none had seroconverted. These findings show the power of network research in discovering infection patterns that standard individual-level studies cannot. Theoretical development and exploratory network research studies may be needed to understand these findings and deepen our understanding of how HIV does and does not spread through communities. Finally, the methods developed here provide practical tools to study “bottleneck” and “firewall” network hypotheses in practice.