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Introduction: The 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. Methods: The 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. Results: The 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]). Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Drug use type and frequency may affect Anti-Retroviral Therapy (ART) uptake for HIV-infected people who inject drugs (PWID). This paper assesses the association between self-reported baseline drug use and ART among HIV-infected PWID in Indonesia, Ukraine and Vietnam. Data on self-reported baseline drug use and ART among HIV-infected PWID at the 26- and 52-week follow-ups were extracted from the HIV Prevention Trials Network (HPTN) 074, a randomized, controlled vanguard study to facilitate HIV treatment for PWID in Indonesia, Ukraine, and Vietnam. Multivariable logistic regression models were fit by study site and the whole HPTN 074 sample, using a 0.5 type I error rate. The response rate were 83.3% and 77.0% at 26th and 52th weeks. At 26-week, baseline use of over one non-opiate/non-stimulant drug was associated with lower odds of ART use among Indonesian participants (OR = 0.21, 95%CI: 0.05–0.82); and baseline injecting drugs for over 20 days in the previous month was associated with lower odds of ART use among all HPTN 074 sample (OR = 0.59, 95% CI: 0.36–0.97). The association of a specific drug use pattern with later ART uptake implies the importance of medication-assisted treatment to enhance ART uptake and adherence among participants. [ABSTRACT FROM AUTHOR]

Background People 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. Methods Participants 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. Results The 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%). Conclusions Viral 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. [ABSTRACT FROM AUTHOR]

Background: Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment. Methods: HPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment. Results: Fifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm. Conclusions: In HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Findings: 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.Interpretation: 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.Funding: US National Institutes of Health. [ABSTRACT FROM AUTHOR]

Objective: Vietnam, Indonesia, and Ukraine have major burdens of IDU and HIV. We estimated the prevalence of depressive symptoms at baseline among people living with HIV who inject drugs, evaluated associations between depression at baseline and 12-month HIV care outcomes and medication-assisted treatment (MAT), and evaluated the study intervention effect by baseline depression subgroups., Design: HPTN 074 was a randomized study. The study intervention included psychosocial counseling, systems navigation, and antiretroviral treatment (ART) at any CD4+ cell count., Methods: Moderate-to-severe depression was defined as a Patient Health Questionnaire-9 score of 10 or above. ART and MAT were self-reported. Eligibility criteria were: 18-60 years of age, active IDU, and viral load of at least 1000 copies/ml. Adjusted probability differences (aPD) were estimated using inverse-probability weighting., Results: A total of 502 participants enrolled from April 2015 to June 2016. Median age was 35 years; 85% identified as men. Prevalence of baseline moderate-to-severe depression was 14% in Vietnam, 14% in Indonesia, and 56% in Ukraine. No evident associations were detected between baseline depression and ART, viral suppression, or MAT at 12-month follow-up. The study intervention improved the proportions of people who inject drugs achieving 12-month viral suppression in both the depressed [intervention 44%; standard of care 24%; estimated aPD = 25% (95% confidence interval: 4.0%, 45%)] and nondepressed subgroups [intervention 38%; standard of care 24%; aPD = 13% (95% confidence interval: 2.0%, 25%)]., Conclusion: High levels of depressive symptoms were common among people living with HIV who inject drugs in Ukraine but were less common in Vietnam and Indonesia. The study intervention was effective among participants with or without baseline depression symptoms., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2019 by The Hastings Center. All rights reserved.)