PROJECT SUMMARY / ABSTRACT Tuberculosis (TB) is the leading cause of death from a single infectious agent and the leading cause of death in people with HIV (PWH). An estimated 8.5 million people with TB are cured every year but many do not return to full health. Up to half of those completing treatment for pulmonary TB have post-TB lung disease, a disabling under-diagnosed group of lung deficits. Lung deficits at TB treatment completion are the strongest predictors of post-TB lung disease severity up to a year later. Alcohol and HIV are associated with lung immune dysfunction and alcohol use is associated with delayed TB diagnosis, increasing the risk of lung injury during active TB disease. However, it is not known whether alcohol use is associated with post-TB lung disease in PWH. We hypothesize that hazardous drinking increases susceptibility to and worsens post-TB lung disease in PWH. Our objective is to investigate hazardous drinking (Alcohol Use Disorders Identification Test [AUDIT] ≥8) as a modifiable risk factor for post-TB lung disease in PWH. To achieve this, we propose an 18- month observational study of 200 PWH completing pulmonary TB treatment in Mbarara, Uganda. We will evaluate the following post-TB lung disease outcomes: functional exercise capacity (primary outcome assessed by 6-minute walk distance), lung physiology (pulmonary function tests), anatomy (CT scan), and lung infections. The primary exposure is past-year hazardous drinking. Secondary alcohol measures will include 30- day Timeline Followback (calendar-based method of alcohol use recall) and phosphatidylethanol (PEth; a biomarker of recent alcohol use). Our expertise spans alcohol use, HIV, TB, pulmonology, epidemiology, and biostatistics. Our primary aim (Aim 1a) is to determine the relationship between past-year hazardous drinking and post-TB lung disease. In Aim 1b we assess the association of past-month heavy drinking and post-TB lung disease progression over time. In Aim 1c we explore whether smoking modifies the association of past- month heavy drinking and post-TB lung disease progression over time. Heavy drinking in Aims 1b and 1c is defined by Timeline Followback as ≥7 drinks/week (women) or ≥14 drinks/week (men) or PEth>200 ng/mL. In Aim 2, we will qualitatively evaluate factors that can improve tailoring of pharmaco-behavioral alcohol and smoking interventions in PWH receiving TB treatment. We will conduct in-depth interviews with 24 PWH during or after inpatient TB treatment and 12 TB healthcare providers. IMPACT: We will determine the association of alcohol use and post-TB lung disease in PWH. Our quantitative and qualitative data will lay the foundation for future work to tailor alcohol and smoking interventions to improve long-term health in HIV/TB co- infection.

PROJECT NARRATIVE Untreated tuberculosis (TB) is deadly, particularly for people with HIV (PWH); but 85% of the 10 million people who fall ill with TB are cured. Despite TB treatment, up to half of TB patients have lung disease that persists (post-TB lung disease). We are 1) studying whether hazardous alcohol consumption contributes to post-TB lung disease in PWH and 2) exploring TB patient and clinician perspectives to design effective interventions to reduce hazardous drinking and improve lung and overall health in PWH who are treated for TB.