Drinkers' Intervention to Prevent Tuberculosis (DIPT Study)

NCT ID: NCT03492216

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 680 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-16
• Study Completion Date: 2022-08-02

Brief Summary

There is an urgent global need to decrease the high mortality of tuberculosis (TB) in persons with HIV as TB is the leading cause of death among persons with HIV worldwide. The DIPT (Drinkers' Intervention to Prevent TB) study is a randomized, 2x2 factorial trial among HIV/TB co-infected adults in Uganda with heavy alcohol use (n=680 persons, 340 each U01). The goal of the study is to determine whether economic incentive interventions can promote both reduced alcohol use and isoniazid (INH) pill taking among HIV/TB co-infected adult heavy drinkers, during isoniazid preventive therapy (IPT: a six-month course of INH) at HIV clinics in southwestern Uganda. Participants will be randomized to one of four arms: Arm 1: no incentives (control); Arm 2: economic incentives for decreasing alcohol use only; Arm 3: economic incentives for IPT adherence only; Arm 4: economic incentives for decreasing alcohol use and for IPT adherence (rewarded independently).

Detailed Description

TB is the leading cause of death among persons with HIV worldwide, and HIV-infected drinkers are at very high risk for TB disease and mortality. Globally, an estimated 25% of persons with HIV are heavy drinkers, and the risk of TB disease is 3-fold higher among heavy drinkers compared to non-drinkers. Six months of isoniazid (INH) preventive therapy (IPT) reduces TB morbidity and mortality by 30-50% above the benefit of antiretroviral therapy (ART). However, INH can be toxic to the liver, and as a result in many high TB/HIV prevalence settings, such as east Africa, heavy drinkers are not offered IPT. Thus interventions to reduce alcohol use are needed to decrease INH toxicity during IPT among HIV/TB infected drinkers. It is also well established that heavy drinkers have poorer ART adherence, and there is growing evidence of reduced IPT adherence in drinkers. However, interventions to reduce drinking have had limited impact on ART adherence, and further interventions to increase IPT adherence among HIV/TB infected drinkers are likely needed.

The use of incentives to promote healthy behavior is a highly effective approach for reducing substance use and for improving adherence to HIV and TB regimens in resource-rich settings. Economic incentives to reduce alcohol use may create a window for safe and effective IPT use over six months by decreasing hepatotoxicity. Decreases in alcohol use may also improve IPT adherence, or additional incentives for IPT adherence may be needed. Such strategies to reduce alcohol use have not been studied in low-income countries and the effectiveness of incentives to optimize IPT in HIV/TB co-infected drinkers is unknown.

OBJECTIVES

Aim 1: Alcohol Reduction Intervention: Determine the effectiveness of economic incentives contingent on point-of-care (POC) urine ethyl glucuronide (EtG) <300 ng/mL (Arms 2 & 4) versus no alcohol incentives (Arms 1 & 3) to reduce heavy drinking over 6 months, among HIV/TB co-infected adult drinkers receiving IPT. The investigators will randomize participants to low-cost escalating prize incentives for EtG negative urine tests at IPT refill visits (Arms 2+4), versus no incentives (Arms 1+3).

Aim 2: INH Adherence Intervention: Determine the effectiveness of economic incentives contingent on POC (IsoScreen) INH urine positive tests (Arms 3 & 4) versus no INH incentives (Arms 1 & 2) on INH adherence among HIV/TB co-infected adult drinkers. The investigators will randomize participants to low-cost escalating prize incentives for INH positive urine tests at IPT refill visits (Arms 3+4), versus no incentives (Arms 1+2).

Aim 3: Impact Assessment of Intervention: Assess the impact of economic incentives on HIV virologic suppression and explore their mechanisms of action, six months after trial completion. The investigators will follow all study participants for six months after trial completion.

1. Assess the impact of the 3 separate incentive interventions (Arms 2, 3, 4) vs. no incentives (Arm 1) on HIV virologic suppression.

2. Explore the mechanisms that may drive the economic incentives to increase virologic suppression. Potential mediators will be reductions in alcohol use and level of IPT adherence.

This study will leverage new low-cost POC tests for alcohol use and INH pill-taking for the first study of incentive-based alcohol and adherence interventions in low-resource settings; these interventions may improve the safety and effectiveness of life-saving medications for heavy alcohol users in many settings.

Conditions

HIV/AIDS; Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Control

All participants will receive brief alcohol and adherence counseling according to Uganda Ministry of Health guidelines.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Escalating incentives (EtG tests)

Escalating incentives for EtG negative urine test (Intervention: Incentives for negative EtG test).

Group Type: EXPERIMENTAL

Incentives for negative EtG test

Intervention Type: BEHAVIORAL

Economic incentives are given to the study participant contingent on point-of-care (POC) urine ethyl glucuronide (EtG) \<300 ng/mL with the amount of the incentive escalating with each subsequent negative EtG test.

Escalating incentives (IsoScreen tests)

Escalating incentives for IsoScreen positive urine tests (Intervention: Incentives for positive IsoScreen test).

Group Type: EXPERIMENTAL

Incentives for positive IsoScreen test

Intervention Type: BEHAVIORAL

Economic incentives contingent on POC (IsoScreen) INH urine positive tests with the amount of the incentive escalating with each subsequent positive IsoScreen test.

Escalating incentives (EtG + IsoScreen)

Escalating incentives for EtG negative tests and for IsoScreen positive urine tests with the incentives rewarded separately (Interventions: Incentives for negative EtG test and Incentives for positive IsoScreen test).

Group Type: EXPERIMENTAL

Incentives for negative EtG test

Intervention Type: BEHAVIORAL

Economic incentives are given to the study participant contingent on point-of-care (POC) urine ethyl glucuronide (EtG) \<300 ng/mL with the amount of the incentive escalating with each subsequent negative EtG test.

Incentives for positive IsoScreen test

Intervention Type: BEHAVIORAL

Economic incentives contingent on POC (IsoScreen) INH urine positive tests with the amount of the incentive escalating with each subsequent positive IsoScreen test.

Interventions

Incentives for negative EtG test

Economic incentives are given to the study participant contingent on point-of-care (POC) urine ethyl glucuronide (EtG) \<300 ng/mL with the amount of the incentive escalating with each subsequent negative EtG test.

Intervention Type: BEHAVIORAL

Incentives for positive IsoScreen test

Economic incentives contingent on POC (IsoScreen) INH urine positive tests with the amount of the incentive escalating with each subsequent positive IsoScreen test.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• HIV-infected adult (≥18 years) prescribed antiretroviral therapy (ART) for at least 6 months;
• Current heavy alcohol use (AUDIT-C positive for prior 3 month drinking and positive EtG urine test);
• Positive tuberculin skin test (TST) (≥5 mm induration);
• AST and ALT <2x the upper limit of normal (ULN);
• Fluent in Runyankole or English;
• No history of active TB, TB treatment, or TB preventive therapy;
• Lives within 2-hour travel time or 60 km of the study site.

Exclusion Criteria

• Prescribed nevirapine (NVP, an ART drug that is declining in usage due to high risk for hepatotoxicity);
• Plans to move out of the catchment area within 6 months;
• Prescribed anti-convulsion medications or history of recurring seizures;
• ALT or AST elevations (>2X ULN);
• Suspected or confirmed active TB as determined by symptom screening and followed by chest X-ray and sputum testing;
• History of prior active TB treatment or prior IPT.
• Pregnant at time of screening

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Infectious Diseases Research Collaboration, Uganda

OTHER

Sponsor Role: collaborator

Mbarara University of Science and Technology

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith A Hahn, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Gabriel Chamie, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Infectious Disease Research Collaboration (IDRC)

Mbarara, , Uganda

Mbarara Regional Referral Hospital (MRRH): Immune Suppression Syndrome HIV

Mbarara, , Uganda

Countries

Uganda

References

Muyindike WR, Fatch R, Lodi S, Emenyonu NI, Kekibiina A, Adong J, Beesiga B, Marson K, Thirumurthy H, McDonell MG, Kamya MR, Chamie G, Hahn JA. Alcohol use and HIV suppression after completion of financial incentives for alcohol abstinence and isoniazid adherence: a randomized controlled trial. EClinicalMedicine. 2025 Jan 8;80:103045. doi: 10.1016/j.eclinm.2024.103045. eCollection 2025 Feb.

Reference Type: DERIVED

PMID: 39867970 (View on PubMed)

Chamie G, Hahn JA, Kekibiina A, Emenyonu NI, Beesiga B, Marson K, Fatch R, Lodi S, Adong J, Thirumurthy H, McDonell MG, Gandhi M, Bryant K, Havlir DV, Kamya MR, Muyindike WR. Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial. Lancet Glob Health. 2023 Dec;11(12):e1899-e1910. doi: 10.1016/S2214-109X(23)00436-9.

Reference Type: DERIVED

PMID: 37973340 (View on PubMed)

Lodi S, Emenyonu NI, Marson K, Kwarisiima D, Fatch R, McDonell MG, Cheng DM, Thirumurthy H, Gandhi M, Camlin CS, Muyindike WR, Hahn JA, Chamie G. The Drinkers' Intervention to Prevent Tuberculosis (DIPT) trial among heavy drinkers living with HIV in Uganda: study protocol of a 2x2 factorial trial. Trials. 2021 May 20;22(1):355. doi: 10.1186/s13063-021-05304-7.

Reference Type: DERIVED

PMID: 34016158 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

17-22727

Identifier Type: -

Identifier Source: org_study_id