maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavitux- imab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 triva- lent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- floxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalentHIV daprivirine TUBERCULO SPLSIS 7013 VI RALPRO HEPA 2000TITIS DermaV ir AGS- 004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bav- ituximab HCV-796 valopicitabine telaprevir TMC207 gatifloxacinD RUGOPC-67683S, DIAG NALOstiVACCS vCP1521, VACCIN EISSS, AP-001ND MRK Ad5 MICROBICIDES IN DEVELOPMENT trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- floxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS- 004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirineTAG raltegravir 2009 VX-950 SCH 503034 taribavirin bav- ituximab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maravirocPipeline TNX-355 apricitabineReport TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- floxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS- 004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bav- ituximab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine JULYraltegravir 2009 VX-950 SCH 503034 taribavirin bavitux- imab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683TREATMENT AL VACTIONAC vCP1521 GROUP ISS P-001 MRK Ad5 triva- lent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximabLEI CHOU, HC V-MARK796 H ARRvalopicitabineINGTON, BOB HUtelaprevirFF, TMC207 gati- RICHARD JEFFERys, JAVID SYED, floxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalentAND CdaprivirineLAIRE WINGFI ELDSPL 7013 PRO 2000 DermaVir AGS- 004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bav- ituximab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- floxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS- 004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bav- ituximab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- floxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS- 004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bav- ituximab HCV-796 valopicitabine telaprevir TMC207 gatifloxacin OPC-67683 ALVAC vCP1521 ISS P-001 MRK Ad5 trivalent daprivirine SPL 7013 PRO 2000 DermaVir AGS-004 maraviroc TNX-355 apricitabine TMC-278 bevirimat etravirine raltegravir VX-950 SCH 503034 taribavirin bavituximab HCV-796 valopicitabine telaprevir TMC207 gati- HIV, TUBERCULOSIS, AND VIRAL HEPATITIS: DRUGS, DIAGNOSTICS, VACCINES, AND MICROBICIDES IN DEVELOPMENT TAG 2009 Pipeline Report JULY 2009 BY TREATMENT ACTION GROUP LEI CHOU, MARK HARRINGTON, BOB HUFF, RICHARD JEFFERYS, JAVID SYED, AND CLAIRE WINGFIELD ABOUT TAG The Treatment Action Group is an independent AIDS research and policy think tank fighting for better treatment, a vaccine, and a cure for AIDS. TAG works to ensure that all people with HIV receive lifesaving treatment, care, and information. You can reach TAG by phone at +1.212.253.7922. To find out more about TAG’s projects go to www.treatmentactiongroup.org. Treatment Action Group 611 Broadway, Suite 308 New York, NY 10012 Tel 212.253.7922 Fax 212.253.7923 [email protected] www.treatmentactiongroup.org ISBN 978-0-9819863-2-6 THIS REPORT IS DEDICATED TO Martin Delaney 1945–2009 Pioneering AIDS treatment activist Founder, Project Inform Table of Contents Introduction 1 Acknowledgments 3 Antiretroviral Drugs in Development 5 Hepatitis B Drug Development in 2009 15 Experimental Oral Agents Therapeutic Vaccines Tuberculosis Treatments 25 Latent TB Infection Active TB Disease Novel Compounds Tuberculosis Diagnostics 39 Health Post Level Peripheral Laboratory Level Reference Laboratory Level Tuberculosis Vaccines 59 Immune-Based Therapies and Preventive Technologies Pipeline 65 Prevention Vaccines Pre-Exposure Prophylaxis Microbicides Immune–Based Therapies Introduction BY MARK HARRINGTON This year’s Pipeline report shows, in brief, a lull in anti-HIV drug development, an alarming stasis in hepatitis B treatment research, renewed activity (after a gap of almost 40 years) in TB drug development, agonizing slow and incremental progress in TB diagnostics research, very preliminary human studies of several new TB vaccine candidates, a back-to-basics mood in the HIV vaccine research community, renewed hopes for efficacy in microbicide and pre-exposure prophylaxis, and no dramatic developments in the areas of immune-based therapies or therapeutic vaccines for HIV. In short, as Thomas Kuhn would have said, this report documents a period of relatively “normal” science, with its incremental steps forward and back, its halting progress, its occasional retreat from a blind alley. There is nothing as dramatic here as the bleak pessimism that enshrouded HIV vaccine research after the STEP study was prematurely terminated in 2007, nor the possibly overhyped HAART 2.0 breakthrough of that same year, when two new classes of anti-HIV drugs were introduced. Yet, as Richard Jefferys points out in the conclusion to his chapter herein, the despair of Berlin 1993 preceded the euphoria of the HAART revolution of Vancouver 1996 by just three years. We do not have a crystal ball; nor do we know whence the next breakthrough may come. Instead, in my view, the greatest challenges to AIDS research this year lie not in the discovery and development of a single new intervention but in the much harder questions of how best to use all the tools at our disposal to prevent and treat HIV. This was put extremely well by Kevin De Cock in his farewell address as the World Health Organization’s HIV director at the PEPFAR Implementers’ Meeting in Windhoek, Namibia, in June, 2009: Martin Luther King said that the arc of the moral universe is long but it bends towards justice. If public health is rooted in the science of epidemiology, its philosophic values are equity and social justice. We are entering perilous ethical and political waters, and current practice for poor people of color in the global South will not be judged well by history if it does not evolve with science and practice in the richer North. … The world cannot allow a permanently two tiered system of global AIDS treatment with late initiation of outmoded drugs reserved for the South. Nor can we hide behind lack of knowledge or the attitude of “let’s wait and see.” Equipoise no longer exists in the debate about early or late initiation, and today’s questions are “treat how early?” and “with what?” 1 TAG 2009 Pipeline Report It is unacceptable, in view of what is at stake—millions of lives, billions of dollars—that despite over three million people in the world on ART [antiretroviral therapy], we cannot definitively answer the question of when to start treatment. Allocation of Global Fund and PEPFAR resources must be based on evidence. There is ethical as well as medical need for a randomized controlled trial to determine optimal starting criteria in Africa, including assessment of the impact of immediate treatment on tuberculosis incidence. PEPFAR and the Global Fund could resolve these questions once and for all through applied research under field conditions, through a large simple trial, for example, with hard end points such as tuberculosis, AIDS, death. Some argue such a study is not needed because we will never have resources to treat more people earlier with better drugs. This is unpersuasive; rationing of health care is a universal reality but let rationing decisions be made transparently, with the involvement of all stakeholders, based on scientific understanding of cost and benefit. Despite challenges, political will and science could get us closer to one, or a few, global, once-