This application proposes the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPT-TB) study, a continuation of the Uganda Alcohol Research Collaboration on HIV (ARCH) cohort of HIV-infected alcohol users in Uganda. Tuberculosis (TB) is the leading cause of mortality in persons with HIV. Isoniazid (INH) preventive therapy (IPT) decreases all-cause mortality and active TB in persons with HIV by 30-50% above and beyond the benefits of antiretroviral therapy (ART) alone. Based on these findings, the World Health Organization (WHO) recommends IPT for all persons with HIV in resource constrained settings, but warns against IPT for persons with ?regular and heavy alcohol use? due to concern for increased hepatotoxicity in heavy drinkers in settings where liver enzymes are not routinely monitored. Approximately one quarter of HIV- infected persons in sub-Saharan Africa (SSA) are heavy drinkers, but no studies have systematically assessed the safety of TB preventive therapy in alcohol users. Thus, the ADEPT-TB study aims to determine the safety and tolerability of TB preventive therapy for HIV-infected drinkers, and examine if the benefits in preventing TB outweigh the risks. Adherence to TB preventive therapy impacts the level of benefit and may also impact hepatotoxicity. Alcohol use is an established risk factor for decreased ART adherence and active TB treatment discontinuation, but it is not known whether HIV-infected drinkers on daily ART can be adherent to TB preventive therapy. Standard IPT is comprised of daily INH for 6-9 months; a shorter-course, such as 3 months of INH plus rifampicin, could improve adherence. The ADEPT-TB study will examine the safety and tolerability of, and adherence to, 6 months of daily INH (6H) and 3 months of daily INH plus rifampicin (3HR) in 380 HIV-infected drinkers in Uganda. We will randomize participants to one of the two regimens (n=190 per arm).
Our first aim i s to evaluate the safety and tolerability within each regimen and by level of alcohol use.
Our second aim i s to compare adherence by regimen; we hypothesize that adherence will be greater in the 3HR arm compared to the 6H arm. Self-reported measures of alcohol use will be augmented by phosphatidylethanol (PEth), an established biomarker of alcohol use. Objective measures of adherence will include electronic pill bottle monitoring and a novel measure of INH exposure, INH concentration in hair. We will actively monitor for hepatotoxicity using the U.S. standard of care for TB preventive therapy for heavy drinkers. We will use the safety, tolerability, and adherence results, together with the known efficacy and mortality benefit of TB preventive therapy in HIV-infected persons in SSA, and an established decision analytic model of TB preventive therapy to conduct our third aim: to determine whether the benefits of TB preventive therapy outweigh the toxicity risks for HIV-infected drinkers in resource limited settings. These data will provide critical insights to inform the guidelines for TB preventive therapy for alcohol-using, HIV-infected persons in TB endemic areas where HIV and alcohol use are common.

Public Health Relevance

The proposed study will build on the Uganda Alcohol Research Collaboration on HIV (ARCH) cohort to (1) evaluate the safety and tolerability of TB preventive therapy for HIV-infected alcohol users, (2) compare HIV- infected alcohol-users' adherence to a 6-month versus a 3-month regimen, and (3) conduct decision analytic modeling to determine whether the benefits of TB preventive therapy outweigh the risks in this population. The results will provide important new data for revisiting the question of how to best deliver TB preventive therapy to alcohol using, HIV-infected persons at high risk for TB disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA020776-08
Application #
9538552
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Lin, Li
Project Start
2011-09-22
Project End
2021-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Woolf-King, Sarah E; Fatch, Robin; Cheng, Debbie M et al. (2018) Alcohol Use and Unprotected Sex Among HIV-Infected Ugandan Adults: Findings from an Event-Level Study. Arch Sex Behav 47:1937-1948
Freiman, J Morgan; Jacobson, Karen R; Muyindike, Winnie R et al. (2018) Isoniazid Preventive Therapy for People With HIV Who Are Heavy Alcohol Drinkers in High TB-/HIV-Burden Countries: A Risk-Benefit Analysis. J Acquir Immune Defic Syndr 77:405-412
Adong, Julian; Lindan, Christina; Fatch, Robin et al. (2018) The Relationship Between Spirituality/Religiousness and Unhealthy Alcohol Use Among HIV-Infected Adults in Southwestern Uganda. AIDS Behav 22:1802-1813
Coleman, Sharon M; Gnatienko, Natalia; Lloyd-Travaglini, Christine A et al. (2018) False-positive HIV diagnoses: lessons from Ugandan and Russian research cohorts. HIV Clin Trials 19:15-22
Hahn, Judith A; Cheng, Debbie M; Emenyonu, Nneka I et al. (2018) Alcohol Use and HIV Disease Progression in an Antiretroviral Naive Cohort. J Acquir Immune Defic Syndr 77:492-501
Fatch, Robin; Emenyonu, Nneka I; Muyindike, Winnie et al. (2017) Alcohol Interactive Toxicity Beliefs and ART Non-adherence Among HIV-Infected Current Drinkers in Mbarara, Uganda. AIDS Behav 21:1812-1824
Asiimwe, Stephen B; Fatch, Robin; Patts, Gregory et al. (2017) Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda. AIDS Behav 21:204-215
Muyindike, Winnie R; Lloyd-Travaglini, Christine; Fatch, Robin et al. (2017) Phosphatidylethanol confirmed alcohol use among ART-naïve HIV-infected persons who denied consumption in rural Uganda. AIDS Care 29:1442-1447
Patts, Gregory J; Cheng, Debbie M; Emenyonu, Nneka et al. (2017) Alcohol Use and Food Insecurity Among People Living with HIV in Mbarara, Uganda and St. Petersburg, Russia. AIDS Behav 21:724-733
Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M et al. (2017) Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women. AIDS Behav 21:2141-2146

Showing the most recent 10 out of 19 publications