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

2. 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

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

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

5. 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

6. 199920002001 20022003 HPTN Science Agenda - Evolution Ongoing Studies Science DevelopmentScience Implementation Application Site Selection New Protocol Development New Study Initiation Concept Prioritization Leadership Selection Capsule Selection

7. 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

8. 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

9. 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

10. 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

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

13.  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

14. 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

15. HPTN Science Development 7 “Go” protocols 7 “Go” protocols 4 pipeline 5 Preparedness protocols 1 HIVNET protocol 2 Discretionary fund protocols May 2001 October 2000 26 capsules From the SWG 13 concepts From the SWG

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

17. 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

18. 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

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

20. HIVNET/HPTN Studies Completed with HPTN Oversight 007 016 pilot (3) USA Zambia 012 032 020 (4)023 (2)025028 (5) Zimbabwe Uganda Malawi South Africa India Thailand 013 (3)

21. Ongoing/Planned Studies – 2003 and Beyond USA 015 (6) 035 037 039 (2) 049 (4) 050 (3) 056 Perú 036 039 (2) Brazil 040 052 Russia 033 Zambia 024 035 (2) 039 (2) 054 055 (2) Zimbabwe 016A (2) 035 (2) 039 043 046 052 Malawi 016A (2) 024 035 (2) 052 (2) Tanzania 024 035 043 046 055 So. Africa 035 (2) 043 046 055 (2) Uganda 012 027 046 054 China 033 (2) Thailand 037 043 052 India 033 034 035 047 052 (2)

22.  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

23.  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