Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings (HARAPAN II)

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis; HIV/AIDS; Tuberculosis; Addiction; Opioid Dependence
• Intervention / Treatment: Drug: Isoniazid; Drug: Rifapentine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 316
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Selangor
    • Kajang, Selangor, Malaysia
      • Kajang Prison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Isoniazid (INH) for 26 weeks; Participants will be randomized to receive INH, the standard of care in Malaysia, for 26 weeks while in prison as TB preventative treatment	Drug: Isoniazid; Participants will be randomized to receive standard INH as TB preventative treatment
Experimental: Short-course isoniazid + rifapentine (INH + RIF) for 12 weeks; Participants will be randomized to receive INH + RIF as TB preventative treatment for 12 weeks while in prison.	Drug: Isoniazid; Participants will be randomized to receive standard INH as TB preventative treatment; Drug: Rifapentine; Participants will be randomized to receive short course INH + RIF as TB preventative treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TB Treatment Completion Rates in Prison	TB treatment completion in prison will be verified using medical records. All TB treatment in prison will be administered under directly observed therapy (DOTs), and treatment administration will be recorded in the participant's prison medical record. Data presented here is the number of participants that completed TB treatment of those that initiated treatment.	3 to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TB Treatment Adherence	TB treatment adherence in prison will be verified using medical records. All TB treatment in prison will be administered under directly observed therapy (DOTs), and treatment administration will be recorded in the participant's prison medical record. Data presented here is the number of participants that adhered to TB treatment of those that initiated treatment.	monthly for up to 6 months
Discontinuation Due to Experiencing an Adverse Event	The number of participants that discontinued the trial due to experiencing an Adverse Event	up to 6 months
Acceptability of Starting the Trial	Acceptability defined as the number of eligible participants that agreed to consent	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
TB treatment tolerability/toxicity measured through liver function tests (AST/ALT levels)	All participants will have their AST/ALT levels (rapid test using a blood sample) checked monthly for abnormal laboratory values (>5 upper limit normal) that may result in adverse events that may be related to TB treatment.	monthly for up to 6 months

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); University of Malaya
• Investigators: Principal Investigator: Adeeba Kamarulzaman, MBBS, University of Malaya; Principal Investigator: Sheela Shenoi, MD, Yale University; Principal Investigator: Frederick Altice, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2017
• Primary Completion (Actual): April 4, 2024
• Study Completion (Actual): April 4, 2024

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 24, 2017

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: prison
• Additional Relevant MeSH Terms: Blood-Borne Infections; Narcotic-Related Disorders; Urogenital Diseases; Genital Diseases; Mental Disorders; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Substance-Related Disorders; Chemically-Induced Disorders; Slow Virus Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Compulsive Behavior; Impulsive Behavior; Actinomycetales Infections; Mycobacterium Infections; HIV Infections; Behavior; Hepatitis; Opioid-Related Disorders; Acquired Immunodeficiency Syndrome; Tuberculosis; Behavior, Addictive; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Isoniazid; rifapentine
• Other Study ID Numbers: 2000020053; 1R01DA041271 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No