The purpose of this study is to conduct empiric studies of tuberculosis (TB) among people in prison with and without a history of opioid dependence. A RCT of latent TB infection prevention strategies among HIV+ and HIV- prisoners with high prevalence of hepatitis C (HCV) using standard 40-week daily isoniazid (40H) vs short-course weekly isoniazid + rifapentine (12HR). Investigators will also use this data, and publicly available data to complete agent-based modeling for comparative and cost-effectiveness of various TB screening and treatment strategies among prisoners.

Screening: All newly admitted prisoners (80-120 new inmates on admission days) undergo a complete assessment, including a brief exam and mandatory rapid HIV test by the prison medical unit. Each prisoner waiting to be evaluated will be invited for participation in TB screening activities (not currently part of standard care). If they verbally assent to wanting to learn more in a group session, their names and ID will be recorded and then invited for informed consent privately, followed by a brief survey, WHO symptom assessment, tuberculin skin testing (TST) with reading after 72 hours, sputum induction on 2 consecutive mornings for AFB smear, TB culture (results back 6-8 weeks using the BACTEC MGIT 960 liquid culture gold standard), and point-of care (POC) Gene Xpert. Each person will have phlebotomy for HBV and HCV Ab, LFTs, and if HIV+, CD4 testing (all of these are POC using Alere™). For those with CD4<50, they will undergo POC low-cost, urinary TB-LAM lateral flow testing (sensitivity=67%) (Alere™ Determine) to identify disseminated TB. Additional demographic, drug use, and TB risks will also be assessed along with prison data (release date, previous incarcerations, type of offense). Participants will then undergo CXR testing. A TB specialist will review all patients and results, ensuring that patients with suspected TB initiate treatment. All suspected or confirmed cases active TB cases in HIV+ prisoners will have ART initiated after 2 weeks of TB treatment initiation (if CNS TB not suspected) if CD4<50 and within 8 weeks for all others.

Trial: All HIV+ and HIV- prisoners with latent TB infection (LTBI) (TST reaction 10 mm or greater) from screening will be asked to participate in the trial. Enrolled participants will undergo block stratified randomization, stratifying on three factors: a) CD4<350; b) HCV Ab status; and c) ART status. After randomization and allocation to 12HR or 40H, participants will be provided 12HR weekly (12 weeks) and INH daily (26 weeks) as directly observed therapy. Every 4 weeks, patients will be monitored for AST/ALT and adverse side effects. Premature treatment discontinuation will occur for any DAIDS Grade 4 toxicity or patient refusal to continue.

The focus of this registration is the RCT. Outcomes measures were updated to match most recent protocol March 2025.

Inclusion Criteria:

Inclusion Criteria (screening):

• Age ≥ 18 years
• Newly admitted inmate at Kajang Prison

Inclusion Criteria (Trial):

• Age ≥ 18 years HIV-1 seropositivity
• Confirmed LTBI (TST ≥ 5mm if HIV+; TST ≥ 10 mm if HIV-)
• Meets DSM-V criteria for opioid dependence
• >9 months before release (to ensure treatment completion in prison)
• AST/ALT < 3x upper limit normal

Exclusion Criteria:

• Unable to provide informed consent
• On a protease inhibitor
• Women who are pregnant or are planning on becoming pregnant

6 months