The aims of this study are: 1. To evaluate using mixed methods the feasibility and acceptability of OUD screening, ED-initiated BUP, and referral. 2. Over the course of the study and as XR-BUP is added to hospital formularies, to estimate the percentage and confidence intervals of patients assessed, treated, and engaged in treatment at Day 30. This will be a three-site study employing a multi-faceted approach to facilitate clinical protocol implementation and to assess feasibility, acceptability, and impact. Investigators will develop, introduce and update site-specific ED clinical protocols and implementation plans for OUD screening, ED-initiated BUP, and referral for treatment. A participatory action research approach will be utilized along with mixed methods incorporating data derived from: Medical record and administrative data abstraction; Research assessments involving patients who are eligible for and willing to receive ED-initiated BUP (including both those who do, and do not, receive BUP); Qualitative interviews, focus groups, and quantitative assessments involving providers and staff, patients, and other stakeholders.

CTN 0064 has two main components: Component 1 is the baseline assessment for CTN 0064. It will also serve as a long-term follow-up assessment for CTN 0049 for those who consent to participate in CTN 0064. Participants whose HCV antibody test result is positive in this baseline assessment will be invited to enroll in Component 2. Component 2 is an RCT that will assess the effectiveness of a Care Facilitation intervention (compared to Control) in moving HIV/HCV co-infected substance users forward along the HCV care continuum. The study's primary objective is based on Component 2 and will be operationalized as movement through a series of (potentially non-sequential) pre-defined, clinical steps along the HCV care continuum (including the ultimate step, sustained virologic response to treatment at 12 weeks post treatment completion [SVR12]) (AASLD/IDSA/IAS-USA). Secondary objectives will be to assess: 1) success at each step in the HCV care continuum, 2) engagement in HIV care and substance use treatment, and 3) HIV viral suppression as well as 4) to examine other long-term outcomes of the CTN 0049 cohort.

This is a 19-week, multi-center, parallel group study that includes: 1) up to 3 weeks for screening; 2) a 13-week Treatment Phase consisting of a 1-week, single-blind run-in period, when all subjects receive twice daily 15 mg acetazolamide capsules (a medication adherence marker), followed by randomization to either twice daily 10 mg lorcaserin or placebo capsules for the remaining 12 weeks; and 3) a 3-week follow-up period, with scheduled visits during Study Weeks 14 and 16.