TB Risk by Alcohol Consumption (TRAC)

Overview

Population:   500 participants for aim 1 (male and female, aged 18 years and older, PLWH), 990 participants for aim 2 (PLWH, who received TPT)

Study Sites:

• Mbarara Regional Referral Hospital Immune Suppression Syndrome (ISS) Clinic, Mbarara, Uganda
• Mbarara City Council Clinic
• HIV clinics in Mbarara, Ibanda and Rubirizi districts

Background:

Tuberculosis (TB) is the leading cause of death among persons living with HIV (PLWH); TB disease rates for PLWH engaging in heavy alcohol use are 2-3 times those of alcohol abstainers and TB treatment outcomes are poorer. There has been little research examining the impact of alcohol use on acquiring new TB infection separately from progressing to active TB disease; this limits our ability to understand the role of alcohol use on the separate phases of TB to optimize intervention strategies most appropriate for each. The TB Risk by Alcohol Consumption (TRAC) Study will examine the risk of acquiring TB infection and of incident active TB disease among PLWH with heavy alcohol use after receipt of TB Preventive Therapy (TPT) in Uganda. Our goal is to inform interventions to reduce the risk of acquiring new TB infection in this group, including behavioral interventions to reduce alcohol use, and TPT strategies, such as repeat short-course TPT to prevent active TB disease.

 Study aims/objectives:

Main Objective: To examine the risk of acquiring TB infection and of incident active TB disease among PLWH with heavy alcohol use after receipt of TPT in Uganda.

Specific objectives:

Aim 1. To estimate the incidence rate of new TB infection among PLWH with prior negative TST results by level of alcohol use.

Aim 2. To determine the incidence of active TB disease among PLWH with prior LTBI, who received TPT, by the level of alcohol use

Study design

Aim 1 study design:  For Aim 1, we propose to re-contact and re-enroll 500 PLWH from the >1700 persons who tested TST negative in ADEPTT and DIPT study screening. We will stratify to enroll approximately 25% (n=133) PLWH with no alcohol use, 25% (n=133) with low to moderate alcohol use, and 50% (n=264) persons with high-risk alcohol use. We will conduct screening for active TB and follow up TST at re-enrollment, and then yearly thereafter, for up to 3 years. Screening for active TB disease will include screening for TB symptoms, using the WHO-recommended symptom screening (cough, fevers, night sweats, weight loss). Those with any symptoms will undergo chest x-ray (if not pregnant), and sputum testing by Xpert MDR/RIF testing to determine whether TB disease is present. TST testing will include placement using purified protein derivative (PPD, Mantoux test), with placement and reading occurring 2-3 days apart, with ≥5 mm induration considered positive. We will conduct behavioral surveys and biomarker specimen collection at re-enrollment and at the yearly visits and will conduct the surveys by phone between in-person visits after re-enrollment. We will also conduct chart reviews to obtain clinical data, such as HIV viral suppression, nadir CD4+ T cell counts, receipt of INH, and interim TB disease diagnoses.

Aim 2 study designs: Aim 2 will be a prospective study to examine active TB disease incidence among all persons enrolled in the ADEPTT and DIPT studies, i.e. PLWH with LTBI, as measured by a positive TST and no active TB disease, who received TPT. We will search the EMRs and TB registries to find all active TB diagnoses. We will conduct tracking to reach persons whose records we cannot locate, as in previous studies. We will use the surveys, INH adherence monitoring, and biomarker testing previously completed in the ADEPTT and DIPT studies for predictors and co-factors of TB disease.