Abstract: The goal of the Clinical Core is to recruit and characterize patient cohorts in Haiti, and to collect and ship clinical samples for studies of tuberculosis (TB) persistence in Projects 1- 3. Core activities will be performed by the Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. GHESKIO is a Haitian non-profit organization which was founded in 1982 and is dedicated to research, service, and training in HIV and tuberculosis. It has conducted NIH supported clinical research for 38 years and has all the essential core components for the conduct of the proposed TBRU studies, including: experienced research staff, out-patient clinics, access to large TB patient populations, a BSL-3 TB laboratory, a data management center, and an institutional review board. In 2019, GHESKIO diagnosed and treated 1,456 patients with culture confirmed TB including 225 re-treatment patients with a second episode of TB, 15 families with multiple siblings with TB, and 321 HIV-negative patients with pulmonary cavity disease and high sputum bacillary load who are at high risk of recurrence after completion of TB treatment. A major focus of this Tri-I TBRU is on post-treatment persistent infection (PTPI) and TB recurrence. Given that more than 1 million of the world’s 10 million cases of TB diagnosed in 2018 were recurrent TB cases, understanding genetic, immunologic and pharmacokinetic correlates for TB persistence and recurrence is critical. The Specific Objectives of the Tri-I TBRU Clinical Core are: 1) Conduct a cross-sectional study of 250 HIV-negative patients with recurrent TB, 250 HIV-negative controls with a single episode of TB, and 50 families with active TB in multiple siblings. Controls with a single episode of TB and post-treatment follow-up will be matched to recurrent cases by age, sex, and time since completion of first TB regimen. There will be a single study visit. Clinical samples including whole blood for host DNA and RNA, serum, PBMCs, urine, and stool will be shipped to New York. 2) Conduct a longitudinal cohort study of 500 HIV-negative drug-sensitive TB patients with pulmonary cavities on chest radiograph, high sputum bacillary load and high risk for recurrent TB. Participants will be enrolled at initiation of anti-tuberculosis therapy (2HRZE/4HR) and followed for 24 months after completion of therapy (30 months total). We estimate that 40 - 50 participants will develop recurrent TB (4- 5 recurrences/100 patient years). M. tuberculosis isolates will be genotyped to determine if recurrence is from relapse of prior infection (estimated 85% of cases) or reinfection with new strain (15%). We will quantify M. tuberculosis in sputum at weeks 1, 2, 3, 4, 8 and 24 weeks during therapy using BACTEC time-to- positivity. We will collect samples including blood, PBMCs, urine, and stool at enrollment, week 2, 4, 8, at the completion of therapy and 3 and 6 months after therapy for analyses by TBRU Projects 1- 3 and PIP Core.