ACTG TB Transformative Science Group Richard E. Chaisson, Chair Diane V. Havlir, Vice-Chair Gavin J. Churchyard, Vice-Chair Sue Swindells, Protocol Development Facilitator

ACTG Clinical Research Sites UNAIDS 2001

TB TSG Membership Richard Chaisson, Johns Hopkins University, Chair Gavin Churchyard, The Aurum Institute, Co-Vice Chair Diane Havlir, University of California, San Francisco, Co-Vice Chair David Alland, University of Medicine and Dentistry of New Jersey Janet Andersen, SDAC Constance Benson, University of California, San Diego Henry Blumberg, Emory University Francesca Conradie, University of the Witwatersrand Helen Joseph CRS Andreas Diacon, Stellenbosch University Kelly Dooley, Johns Hopkins University Jennifer Furin, Case Western Reserve University Devasena Gnanashanmugam, DAIDS Amita Gupta, Johns Hopkins University Richard Hafner, DAIDS Mark Harrington, Treatment Action Group Elizabeth Hawkins, Network Coordinating Center Robert Horsburgh, Boston University Lynne Jones, Data Management Center Cecilia Kanyama, Malawi CRS Serena Koenig, Harvard University Annie Luetkemeyer, University of California, San Francisco Gary Maartens, University of Cape Town Vidya Mave, BJ Medical College CRS Alberto Mendoza, Barranco CRS John Metcalfe, University of California, San Francisco Flavia Miiro, JCRC/Kampala CRS Sachiko Miyahara, SDAC Payam Nahid, University of California, San Francisco McNeil Ngongondo, Malawi CRS Eric Nuermberger, Johns Hopkins University Elisha Okeyo, KEMRI/CDC CRS Parita Rathod, Network Coordinating Center Ian Sanne, Wits HIV CRS Tejaswi Sevekari, BJ Medical College CRS Kim Scarsi, University of Nebraska Medical Center Sarita Shah, Center for Disease Control Susan Swindells, University of Nebraska Medical Center Robert Wallis, The Aurum Institute

The TB TSG Scientific Agenda 1.0 TB TREATMENT SHORTENING To identify regimens to shorten Drug-Susceptible TB treatment to ≤3 months in patients with and without HIV 2.0 MDR-TB TREATMENT To identify regimens for MDR TB treatment in <6 months in patients with and without HIV 3.0 PREVENTIVE THERAPY To identify regimens to treat latent TB in 1 month and MDR-TB infection in 6 months; to improve latent TB therapy in HIV-infected individuals

The TB TSG Scientific Agenda 4.0 TB/HIV CO-TREATMENT To optimize the treatment of TB/HIV co-infection To evaluate and minimize drug-drug interactions 5.0 TRANSFORMATIVE SCIENCES Pharmacology Biomarkers Laboratory monitoring and diagnostics Host-directed therapies

ACTG TB Treatment Studies Study Description Status Accrual/Target A5307 Essentiality of INH in the initial phase of TB therapy, a comparison with moxifloxacin Phase 1 EBA trial Completed 63 A5344/ STAND Phase 3 trial of Pa824/Moxi/PZA to shorten TB therapy to 4 months (with TB Alliance) On hold /400 A5349/ TBTC 31 Phase 3 trial of rifapentine + moxifloxacin to shorten TB therapy to 4 months Enrolling 118/1250 A5290 A5362 LPV/r + DTG in patients on TB therapy A Phase IIc Trial of Clofazimine for Treatment Shortening in DS TB Closed to accrual In development 71/60 /696

MDR TB Protocol Status Study Description Status Accrual/Target A5312 Early bactericidal activity of high-dose INH in patients with MDR TB and inha mutations Enrolling A5343 PK safety study of bedaquiline and delamanid in patients with MDR TB in South Africa 3/84 A5356 Linezolid dose-finding ranging study with delamanid and an optimized background regimen without injectables In development /240

TB preventive therapy Studies Study Description Status Accrual/Target A5279 Daily Rifapentine/INH for 1 month vs INH for 9 months to prevent TB in HIV+ patients In follow up till 11/2017 Enrolled 3000 participants as of 11/2014 Phoenix A5300/ P2003 Phase 3 trial of delamanid vs INH for high-risk contacts of M/XDR TB patients (with IMPAACT) Pilot study completed, main study in development 308 IC/1018 HHC enrolled in 6 mos Main study: /1726 IC /3452 HHC A5365 Cycled Ultra-Short Course Preventative INH/RPT in HIV in Medium to High TB-Endemic Areas In development /3132

TB Transformative Sciences Studies Study Description Status Accrual/Target A5302 BioBank for Surrogate Marker Research for TB (B-SMART) With TB Alliance and TBTC Enrolling at limited sites /300 A5338 Pharmacokinetic Interactions among DMPA, RIF, and EFV in Women co-infected with HIV and TB (PRIDE-HT) Enrolling 29/46 A5289 Adaptive phase II safety and PK of sutezolid with rifampin or rifabutin in drug-susceptible TB In development /182

TB TSG Progress Report TB TSG is pursuing an ambitious portfolio of TB trials: HIV/TB co-management (A5290, A5338) Shortening TB treatment (A5307, A5344, TBTC 31/A5349, PR698, A5289) MDR TB (A5343, A5356, A5312) Latent TB infection (A5279, PR726) Latent MDR TB infection (A5300/I2003 – PHOENIx) Partnerships are essential for conducting TB clinical trials: TBTC – Study 31 TB Alliance – STAND TBTC and TB Alliance – Biomarkers IMPAACT – Phoenix Pharma (Sanofi, Otsuka, Janssen) – multiple studies

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