Clinical trial NCT03492216: Drinkers' Intervention to Prevent Tuberculosis (DIPT Study)
Official title: Drinkers' Intervention to Prevent Tuberculosis (DIPT Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV/AIDS
Tuberculosis
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Infectious Diseases Research Collaboration, Uganda
name: Mbarara University of Science and Technology
First posted: 2018-04-10
Enrollment: 680
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With and Without Non-hazardous Drinking, as Determined by Self-report and the Biomarker Phosphatidylethanol, at 3- and 6-months.
timeFrame: Both 3 months and 6 months (composite measure)
measure: Number of Participants With >90% Isoniazid (INH) Adherence During Prescribed Course of INH
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants With Hepatotoxicity Resulting in Isoniazid (INH) Discontinuation.
timeFrame: up to 9 months
measure: INH Concentration in Hair
timeFrame: 3 and 6 months
measure: Number of Participants With and Without HIV Viral Suppression at 12 Months
timeFrame: 12 months
measure: Number of Participants With Active Tuberculosis (TB).
timeFrame: 12 months
Other outcomes:
Locations:
city: Mbarara
country: Uganda
facility: Infectious Disease Research Collaboration (IDRC)
city: Mbarara
country: Uganda
facility: Mbarara Regional Referral Hospital (MRRH): Immune Suppression Syndrome HIV
Study officials:
affiliation: University of California, San Francisco
name: Judith A Hahn, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Gabriel Chamie, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.