HIV Prevention Trials Network Update Africa Regional Working Group 20 May 2003

HPTN Purpose Established in 1999 by NIH Consortium – NIAID, NICHD, NIMH, and NIDA, including support from Fogarty and OAR:  To address a continuing unmet need in HIV prevention science in six research areas  To evaluate highest priority non-vaccine HIV prevention approaches in diverse settings

HPTN Uniqueness  HIV prevention endpoints  Worldwide clinical trials network  Multi-site, multi-trial capacity  Multidisciplinary approach  Oversight by NIH DSMB, and External Advisory Group

Science Development and Prioritization Resource Mobilization and Optimization SitePreparation and Support HPTN TRIALS The HPTN Components

Identify, develop, and evaluate HIV prevention interventions in six research areas  Antiretrovirals for HIV Prevention  Perinatal  Microbicides  STD Control for HIV Prevention  Behavioral  Substance Use HPTN Scientific Agenda

HPTN Science Agenda - Evolution Ongoing Studies Science DevelopmentScience Implementation Application Site Selection New Protocol Development New Study Initiation Concept Prioritization Leadership Selection Capsule Selection

HPTN Key Accomplishments - 1  10 HIVNET studies overseen  19 protocols developed  15 studies in field since 1999  9 studies completed  14,000 participants enrolled  >90% participants retained

HPTN Key Accomplishments - 2  15 New international sites/subsites  12 AITRP (Fogarty) awards per year  Research Ethics Guidance Document  Community coordinators in all sites  Documented Good Clinical Practices (GCP) training in all sites

HPTN Central Laboratory (CL) Johns Hopkins/ Univ of Pittsburgh HPTN Central Laboratory (CL) Johns Hopkins/ Univ of Pittsburgh HPTN Coordinating and Operations Center (CORE) Family Health International HPTN Coordinating and Operations Center (CORE) Family Health International HPTN Statistical and Data Management Center (SDMC) FHCRC/UWash HPTN Statistical and Data Management Center (SDMC) FHCRC/UWash Central Leadership in HPTN

Site Leadership in HPTN Boston Providence New York Philadelphia Birmingham San Francisco Los Angeles Seattle Perú Brazil Uganda Tanzania Malawi (2) Zambia Zimbabwe South Africa India (2) Thailand China (2) Russia

HPTN Governance Executive Committee Prevention Leadership Group PerinatalMicrobicidesBehavioralSTD Control AntiretroviralSubstance Use Community Working Group Ethics Working Group Science Working Groups

 Science flows from SWG foundation  Priorities established by Executive Committee  Network QA for scientific excellence via 3 standing committees  Network reviews staged to study progress HPTN Scientific Processes – Internal Goals

Executive Committee (EC) members applied these criteria to each concept to arrive at HPTN priorities  Scientific merit  Public health impact  Research advantage of the HPTN HPTN Scientific Prioritization – Criteria

HPTN Science Development 7 “Go” protocols 7 “Go” protocols 4 pipeline 5 Preparedness protocols 1 HIVNET protocol 2 Discretionary fund protocols May 2001 October capsules From the SWG 13 concepts From the SWG

HPTN Scientific Quality Assurance Science Implementation Science Dissemination Science Development Protocol Review Committee Prevention Leadership Group Executive Committee Study Monitoring Committee Manuscript Review Committee

Infrastructure Building - Sites  $160M to global sites over past decade  5 preparedness studies at 13 sites to assure site operational quality  Fogarty training link  Laboratory training, specimen tracking, storage and shipment  Internet connectivity and data management system

Infrastructure Building – Ethics/Community  Ethical challenges of US-sponsored research in resource-poor countries  HPTN Ethics Guidance Document  Synthesize emerging ethical thinking  Establish practical procedures for meeting ethical challenges within HPTN  Enhance and support Community Advisory Boards at each site, plus 3 Regional Working Groups

 Current FY’03 funding - $64M  Supplemental request to NIH  RO1 support  USAID support  Pharmaceutical support HPTN Resource Mobilization – January ‘03

HIVNET/HPTN Studies Completed with HPTN Oversight pilot (3) USA Zambia (4)023 (2) (5) Zimbabwe Uganda Malawi South Africa India Thailand 013 (3)

Ongoing/Planned Studies – 2003 and Beyond USA 015 (6) (2) 049 (4) 050 (3) 056 Perú (2) Brazil Russia 033 Zambia (2) 039 (2) (2) Zimbabwe 016A (2) 035 (2) Malawi 016A (2) (2) 052 (2) Tanzania So. Africa 035 (2) (2) Uganda China 033 (2) Thailand India (2)

 Network capacity to support large trials  Product availability for key trials  Meeting GCP standards across sites  Laboratory quality in impoverished settings HPTN Challenges in 2003

 Unmet need for state of the art HIV prevention science  Internal quality assurance for scientific excellence  Flagship Network for building international HIV research activities  Registrational standards being applied Conclusions