"HIV Vaccine Development: Enabling the efforts through policy development" Dr Saladin Osmanov

1. WHO/UNAIDS/UNSW Satellite Session"Access to care and treatment in the context of HIV vaccine and other prevention trials" IAS Conference, 22 July 2007, Sydney, Australia "HIV Vaccine Development: Enabling the efforts through policy development" Dr Saladin Osmanov Coordinator WHO-UNAIDS HIV Vaccine Initiative World Health Organization Geneva, Switzerland

2. An international landscape in the field ofHIV Vaccine R&D in 2007 • The 2005-2007 G8 Summits re-affirmed the highest political level of support to global initiatives to accelerate the development of HIV vaccines, such as Global HIV Vaccine Enterprise • Multiple national and international programmes (e.g., NIH/HVTN, Walter Reed, IAVI, EU/EC, ANRS, Sweden, Italy and others) expand their efforts in the development and conducting clinical trials with promising HIV vaccine candidates based of multiple vaccine concepts • The Bill & Melinda Gates Foundation provides the first grants for the establishment of the Collaboration for AIDS Vaccine Discovery (CAVD), including 11 vaccine-discovery consortia and 5 centralized facilities • Growing number of low- and middle-income countries participating in preparation and conduct of HIV vaccine clinical trials

3. Need to conduct multiple efficacy trials,especially in developing countries

4. Continuum of the WHO-UNAIDS Efforts in the Area of HIV Vaccine R & D • 1989-2000: WHO HIV vaccine research activities initiated by the WHO Global Programme on AIDS (GPA) and continued with UNAIDS from 1995-2000 • 2000-2007: Establishment and functioning of a joint WHO-UANIDS HIV Vaccine Initiative (HVI) • Strategic and technical guidance provided by the WHO-UNAIDS HIV Vaccine Advisory Committee (VAC), Chaired by Prof David Cooper • Since October 2006: HVI has been tasked to coordinate its activities with Malaria and TB vaccine R&D, focusing on: Policy development, Regulatory research and Ethics

5. WHO/UNAIDS priorities in the area of HIV vaccine R&D • Maintain high level of advocacy to facilitate the development of globally effective and accessible HIV vaccines in alignment with major international partners (e.g, Global HIV vaccine Enterprise) • Support comprehensive and sustainable capacity strengthening and networking of trial sites in developing countries integrated into overall vaccine R&D efforts for diseases of public health importance, such as HIV, malaria, TB and others • Facilitate the development and implementation of internationally agreed norms , standards and policies for the development, evaluation and future access to HIV vaccines

6. Addressing ethical challenges in support of vaccine-related research and clinical trials 2000 Ethical Guidelines Guidance Point 16: “Care and treatment for HIV/AIDS… should be provided to participants…, with the ideal being to provide the best proven therapy, and the minimum to provide the highest level of care attainable in the host country in light of (circumstances specified)” 2004 WHO/UNAIDS Consultation“… there is broad, though not unanimous, agreement among sponsors of HIV vaccine trials that ART and a clinical care package should be provided to those who become infected during the conduct of a trial

7. However, a number of outstanding questions remain unresolved • What level of care or standard, to whom, for how long, and who's obligation? • Disagreement on obligations to provide ART to those who are excluded during the screening process because they are HIV positive. • Disagreement on obligations to provide treatment of HIV in non-HIV vaccine trials: e.g. to participants who are screened and test positive for HIV during TB, malaria or cholera vaccine trial enrolment.

8. Extensive WHO/UNAIDS Regional Consultations inAfrica, Latin America, Asia, Eastern Europe in 2005-2007 • To review ethical principles and guiding documents • To map out scenarios from practical field situations facing challenges in determining what care and treatment to provide • To develop a process for formulating care and treatment plans in vaccine trials • To identify potential solutions for improved care and treatment plans Position paper has been published in Vaccines journal 2007

9. Inclusion of Women and Adolescents in HIV Vaccine trials:Reports published in AIDS journal in 2005 and 2007 • More than 95% of cases in developing countries • More than 50% of cases among young people of 15-24 years • More than 40% of cases among women • Up to 10% of cases among children younger than 15 years

10. WHO/AAVP Consultation on:“Inclusion of Adolescents in HIV Vaccine Trials”16 - 18 March, 2006, Gaborone, Botswana Recommendations: • Product development: safety, immunogenicity, duration of immunity, routes of administration, etc. • Legal, Regulatory and Ethical: e.g., definition of age of consent, confidentiality, "statuary rape" • Clinical trial design and trial endpoints: e.g., HIV infection in younger adolescents • Community acceptance and participation Report accepted for publication in AIDS journal 2007

11. Regulatory Challenges and Related Policies - Production of candidate vaccines for clinical trials (GMP) - Immunogenicity and potency measurement - Safety monitoring • Effective mechanisms for regulatory/ethical review, approval and oversight of clinical trials • Understanding of novel efficacy trials concepts and their potential for licensing and the development of immunization strategies: - Phase IIB-TOC trials (WHO/UNAIDS/IAVI Consensus meeting) - Definition of HIV Vaccine Efficacy (WHO/UNAIDS/Enterprise Consultation is planned on 5-6 Sept.07 in Paris)

12. UNAIDS/WHO/IAVI Consensus MeetingNew York, Jan 31-Feb 2, 2006 • Discuss issues related to the definition of intermediate phase of IIB-Test of Concept (IIB-TOC) trials and their position in the overall pathway of HIV vaccine R&D. • Make recommendations for: • situations where such trials could be of the greatest (or the least) utility; • Issues related to preparation for, and conduct of IIB-TOC trials, particularly with respect to conveying the correct messages to governments, national regulatory authorities, communities and participants; • implications for product development, manufacturing, and potential licensing Report has been published in AIDS journal Nov 2006

13. Strategic elements to create favorable environment in support of HIV vaccines trials in developing countries Government willingness & commitment Public (media) attention National Capacity Building - Clinical trial and Laboratory expertise Data management Community involvement International collaboration Epidemiology Virus Monitoring Regulatory & Ethical Frameworks Scientific infrastructure Availability of cohorts Social behaviour expertise

14. National AIDS Vaccine Plans and Strategies Initiated in 1992 in Brazil, Thailand and Uganda. Continued in several other countries. Facilitate trials by describing policies, approval mechanisms, research priorities A framework for coordinated plan of capacity building and site development Brazil: Second generation (2000)

15. New Generation of National AIDS Vaccine Plans/Strategies NORMATIVE FRAMEWORK Regulatory Ethical Logistical Political Legal TECHNICALCOMPONENTS Virology Epidemiology Socio/ behavioural Clinical trials Media/ PR Etc SUPPORTING ENVIRONMENT Community support HIV/AIDS Prevention Access to care, incl. ART Infrastructure/ human resources Etc

16. The African AIDS Vaccine Programme (AAVP) was launched in 2000 • The AAVP is a network of African scientists and community, working together to promote and facilitate HIV vaccine research and evaluation in Africa, through capacity-building and regional and international collaboration (“the voice of Africa”). • Activities being developed and implemented through six thematic working groups: • Advocacy, information and resource mobilization. • Biomedical sciences (laboratory and clinical). • Population studies (Epidemiology and Socio-Behavioural issues). • Ethics, Law and Human Rights. • National Strategic Planning. • Community

17. Increasing participation of African countries in HIV vaccine trials 2000 2006 2008 > 4 000 volunteers ? 12 countries 400 volunteers 8 countries 15 trial sites 2010 50 volunteers 1 country >10 000 volunteers

18. Opportunities and Challenges for Global Networking and Policy Development in Support of HIV Vaccine R&D • Unity of Mission and Shared Vision: • Development of safe, globally effective and affordable for all countries in the region • Balanced focus on all aspects vaccine R&D and clinical trials, ensuring the highest scientific, ethical and regulatory standards • The Key Challenges: • Coordinate and promote regional and global collaboration in alignment with the global HIV vaccine agenda (e.g., HIV Vaccine Enterprise) • Optimize - capacity building & site development • Develop unified clinical trial platforms on global and regional basis • Careful assessment, development and harmonization of sensitive policies based on extensive consultation with all stakeholders • Actively involve communities, create/maintain and support favourable environment in support of vaccine trials