This is an open-label, randomized, pilot trial of XR-NTX vs. treatment as usual (TAU) for treatment of opioid and alcohol use disorders in HIV-infected patients, whose goal is to determine the acceptability and feasibility of XR-NTX in HIV practice and inform development of a multi-site comparative effectiveness trial of XR-NTX vs. TAU in HIV clinics. During the study start-up period, we will conduct a survey of HIV provider attitudes toward opioid antagonist therapy at 15 high-volume HIV clinics to assess willingness to prescribe antagonist therapy and inform the site selection process (Aim 1). During pilot study implementation, we will survey HIV-infected patients regarding attitudes toward opioid antagonist therapy (Aim 2), track rate of participant recruitment (Aim 3), and randomize those who have untreated opioid and/or alcohol use disorders to receive XR-NTX vs. TAU (Aim 4). Participants will attend study visits every 4 weeks for 16 weeks. Treatment initiation will be assessed at 4 weeks and retention at 16 weeks (4 XR-NTX injections). Randomization will continue until a maximum of 50 participants or 12 months are reached. Pilot study duration will be a maximum of 17 months (maximum 12 months recruitment + 5 months study participation for those enrolled at the end of the recruitment period). We will assess feasibility of a multi-site trial of XR-NTX vs. TAU by addressing four pilot study specific aims.

The primary objective is to follow a group of participants with opioid use disorder to estimate treatment-as-usual rates of opioid use clinical outcomes following discharge to the community from detoxification and/or short-term residential programs. This is an observational study of participants with opioid use disorder leaving the same detoxification and/or short-term residential units from which participants for CTN-0051 are recruited, but who are discharged to TAU in the community. We will collect similar drug use measures as are collected in CTN-0051 that will allow us to estimate (1) days to first use and days to regular use, (2) number of days of use during the first four and eight weeks post-discharge to the community, and (3) number of positive, negative and missing UDSs at weeks 1, 4 and 8 post-discharge to the community.