CDC Activities in TB/HIV Research Perspectives on Using Research to Strengthen and Inform Programs Charles D. Wells, MD Chief, International Research and Programs Branch Division of Tuberculosis Elimination U.S. Centers for Disease Control and Prevention 14 February 2005

TB/HIV Research at CDC Mission To conduct applied practical research for improving TB & HIV program capacity for better control of HIV-associated TB To evaluate impact of interventions To contribute to broader evidence base for TB/HIV policy, guidelines, recs. (dx & rx) Groups DTBE – IRPB, TBTC, MLB, etc. GAP – C&TB, S&IDB, country-level programs Partners – MOH, USAID, WHO, MRC, KNCV, IUATLD, NIH, PATH, etc.

Major Areas of Focus Surveillance Epidemiology TB case finding OR capacity building TB prevention MDRTB / HIV Diagnosis Treatment

Surveillance NTP strengthening and foundation for research TB recording/reporting - ETR & ETR.net Patient-based – WHO core data 7 SS African countries HIV data collection Thailand – electronic reporting, HIV and DR surveillance in 4 HB provinces + BMA TB/HIV surveillance capacity building project (PEP) DR surveillance – Botswana with ↑ DR New tools - Oraquick® on sputum (Botswana)

Epidemiology Epidemiological studies HIV risk factors - Botswana Treatment default - Botswana & S Africa Impact of ARV’s on TB epi – Brazil Thailand TB/HIV observational cohort study Prospective, comprehensive Evaluate mortality risk factors Impact of interventions Evaluating tools: ARTI - Botswana, 2002-2004 Latin squares sampling - ↓ sample size, trends ARV and IPT program roll out

TB Case Finding TB screening in context of HIV CT (VCT) settings IPT pilot, Botswana, 2000-01 CXR limited value in asymptomatic attendees Comparing enhanced TB screening to current standards - Ethiopia Yield of CXR screening – Vietnam and Kaliningrad Integrating TB screening in roll out of diverse HIV CT program in SA Broader evaluation of TB CF among focus countries

Operations Research Capacity Building Adapting general TB OR training for NTPs USAID supported Course + proposals/funding + mentorship 10 trainings, 200 staff, 55 proposals Modified for TB/HIV OR training More targeted lectures and field exercise FSU/Baltics – 11/04 3 national projects – treatment adherence, nosocomial transmission, cross-referral Africa TB/HIV OR course – Malawi, 6/04

TB Prevention IPT pilot – Botswana, 2000-2001 600/1000 started IPT, 70% completed Symptom screen sufficient MOH IPT program roll out, 2003 >8,000 enrolled on IPT Info system, evaluation late 05 DR monitoring – 1995-96, 1999, 2002, late 2005 IPT trial of duration (6 mos vs. 3 yrs), 11/04 N=1800; R/DB/PC; builds on IPT program TBTC Study 26, on-going 3 mo H/RPT vs. 9 mo H; 4000 enrolled Substudies – viral hep, peds PK

MDR TB / HIV E Europe (Russia, Baltics) TB screening and PT OR (Orel and Kaliningrad) Baltics – rapid dx, evaluate PT strategies Africa Botswana - DRS ‘05 to evaluate link of DR with HIV South Africa – MRC leadership MDR TB outcome studies (effects of HIV) ARV’s + MDR TB treatment – MRC/CDC Airborne Infection Research (AIR) Facility Transmission/IC intervention studies

Diagnosis Smear negative study Prospective, case-control study Abx non-response predictive of cx+ TB Sero-diagnostic studies, Botswana Adult: 4 assays, 15% dx by blood cx alone Peds: 2 assays; 16% micro confirmation Algorithms for TB diagnosis TB/HIV cohort study (MGIT), Thailand FIND collaboration – evaluate MGIT feasibility (GAP/DTBE) Line-probe assay - rapid dx of R res, Latvia/Vietnam Feasibility & CE

TB Treatment Operational (ARV access/delivery) HIV CT in TB clinical settings (Opt out – Botswana) MRC/CDC project in KZN of ARV initiation among hosp. TB patients (3/05) Clinical TBTC Study 27 HRZE vs. HRZMox, 50% enrolled, 2 mo cx conv. TBTC Study 28 HRZE vs. MoxRZE, 2 mo cx conv., 4/05 Empiric treatment studies