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

2. ACTG Clinical Research Sites
UNAIDS 2001

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. THANK YOU