HIV Prevention Options for Women: Microbicides Martin Methot August 10, 2006

1. International Partnership for Microbicides HIV Prevention Options for Women: Microbicides Martin Methot August 10, 2006

2. Outline of Presentation • The Face of HIV Globally • What is a Microbicide? • International Partnership for Microbicides (IPM) • Quotes from leaders in the HIV/AIDS field

3. The Face of HIV Globally • Increasingly female • In Sub-Saharan Africa, 74% of young people (aged 15-24 years) living with HIV are female • In Asia, 30% of all adults living with HIV are female (and new cases are occurring faster in women) • Female HIV infections are also on the rise in Eastern Europe and Latin America • In South Africa – 1 in 4 women infected by age 22 • Married, monogamous • In India – 22% of cases in housewives with single partner • Mothers World Bank Photos

4. Current HIV Prevention Strategies • Abstinence • Delay first sexual act • Be faithful • Male and female condoms • Behavior change • Treatment of sexually transmitted infections

5. Other Prevention Strategies Under Research • Male circumcision • Cervical barriers (diaphragm) • Pre-exposure prophylaxis with ARVs • Herpes suppression • HIV Vaccines

6. Marriage and Motherhood as Risk Factors • Marriage and women’s own fidelity not enough to protect them against HIV infection • Many women infected, despite staying faithful to one partner: 66% of women surveyed in Zimbabwe and South Africa reported one lifetime partner – and 40% were HIV positive • According to the UN: 56% of pregnant women between 25 and 29 in Swaziland HIV positive – the highest prevalence in 5 years

7. Women’s Vulnerability • Women's susceptibility to HIV infection • results from a combination of biological, social and cultural factors • Young women are at highest risk of HIV infection due to: • an immature physiology • inequitable gender norms – climate that accepts exploitation and violence towards girls • prevalence of transactional sex, coupled with liaisons and marriages between girls and older, more sexually experienced men

8. The Need for HIV Prevention Initiated by Women • Most HIV infections are spread by unprotected sex • Most current methods are male-initiated and contraceptive • Women have no means to protect themselves if their partners do not use male condoms or allow female condoms • Abstinence and being faithful are not likely to protect married women or those who are sexually abused

9. What is a Microbicide? • Substance that can prevent transmission of HIV when applied to the vagina • Could be made in many forms: • gel or cream • sponge • film • suppository • vaginal ring or diaphragm

10. The Ideal Microbicide • Safe- must have no localized toxicity • Effective- must have a significant degree of efficacy in routine use • Cheap- pricing strategy must optimize distribution and availability • User-friendly- must be compatible with use during sex, and acceptable to women and their partners Robin Shattock, St George’s, University of London

11. Delivery Methods Vaginal ring (above) Vaginal applicator (right) and applicators being filled (above)

12. Comprehensive Approaches to HIV/AIDS Prevention Treatment and Care Prior to Exposure Time of Exposure Prior to Exposure Point of Transmission Vaccines Male and female condoms Anti-retroviral therapies Pre-exposure prophylaxis Opportunistic infection therapies Anti-retroviral therapies (mother-to-child) STI treatment Behavior change Basic care Microbicides Microbicides offer a woman-initiated method to reduce HIV transmission

13. First Generation Microbicides • Products that form physical barriers to HIV or change the chemistry of the vagina to boost up defenses against HIV • In most advanced stage of clinical trials • But likely to be only partially effective

14. Current Clinical Efficacy Trials

15. Next Generation Microbicides • Next generation microbicides • Specifically active against HIV • Include microbicides that use antiretroviral drugs • Examples: Tenofovir/PMPA gel, Dapivirine/TMC120 gel, UC-781 • In safety trials in humans • Highly active, can be formulated for slow release • Future of microbicides is likely in combinations • Two or more mechanisms of action included in one product to increase effectiveness

16. AIDS Therapy Timeline

17. Source: Alliance for Microbicide Development Microbicide Trial Sites

18. Ethics of HIV Prevention Trials • Informed consent • Family planning counseling • Pre/Post HIV-testing counseling • Referrals for those screening positive • Treatment of STIs • Treatment of those who become HIV-infected during the trial • Treatment of adverse reactions • Resistance

19. Urgency and Access • Historically, it can take decades for scientific innovation to reach the developing world • The microbicide field is committed to speeding up availability of effective products - reaching those who are most in need first • Microbicides must be widely available and affordable

20. Key Challenges • Expand pipeline of promising compounds • Promote community engagement at trial sites to ensure community and national ownership • Significantly increase funding for microbicide research and development • Encourage international leaders to support microbicides as part of a comprehensive response to HIV/AIDS

21. Funding for Microbicide Field

22. Cost and Financial Gap • In 2005 the global community spent just over $160 million for microbicide research and development. • Funding for the microbicide field needs to double to nearly $300 million annually to accelerate product development.

23. IPM Mission IPM’s mission is to prevent HIV transmission by accelerating the development and availability of safe and effective microbicides for use by women in developing countries.

24. Opportunities For Action 1. Assess and fund across the microbicide portfolio Coordinate effort to ensure widespread availability and adoption 4. Optimize clinical trial capacity Pre- clinical Clinical trials Basic research Discovery Launch 3. Provide common capabilities or supports for the field 2. Help develop the “next generation” of microbicides Formulation capacity In vitro and in vivo models Regulatory Manufacturing Multiple mechanisms/ targets/products

25. Pharmaceutical Partners • IPM in-licensed compounds from three large pharmaceutical companies: • TMC120 or Dapivirine - from Tibotec Pharmaceuticals/ Johnson & Johnson • M167 - from Merck & Co. • BMS793 - from Bristol-Myers Squibb • Royalty-free rights to develop, manufacture and distribute microbicides in developing countries

26. IPM Clinical Trials: TMC120 Safety • First use in Africa • Expanded safety (42 days use, 112 women) • Sites: • Kigali, Rwanda(with Project Ubuzima) • Moshi, Tanzania(with KCMC & Harvard) • Johannesburg, S. Africa(with Univ. of Witwatersrand) • Bloemfontein, S. Africa(with FARMVOS-Parexel)

27. Delivery Systems • The delivery vehicle for an active drug is just as critical as the active itself. • Semisolids: gels (including once-a-day gels), creams, lotions, emulsions • Develop “non-coitally dependent” microbicides and vehicles allowing for slow release: vaginal rings

28. Leaders Speak “Quite frankly, I find it extraordinary that the search for an effective and safe vaginal microbicide has been progressing so slowly. Particularly as we know that microbicides are a real possibility.”  Dr. Peter Piot, Executive Director, UNAIDS “The women of Africa need new prevention options. They are at tremendous risk for HIV, so they should be empowered with an option to reverse the pandemic. Microbicides will put HIV-prevention into their hands”. Mrs. Graça Machel, President, Foundation for Community Development, Mozambique

29. Leaders Speak (cont.) “Making microbicides available, accessible and affordable for women is one of the greatest and most significant contributions the world can make for women to protect themselves from HIV infection”. Ms. Anandi Yuvaraj, India HIV/AIDS Alliance “ Gender inequality is driving the virus, and that is why the microbicide potential is perhaps in the immediate future the most significant potential of all”. Mr. Stephen Lewis, U.N. Special Envoy for HIV/AIDS in Africa

30. Leaders Speak (cont.) “If we’re going to end AIDS, we have to keep working on vaccines, microbicides and other prevention strategies”. Mr. Bill Clinton, The Clinton Foundation “If I had a magic bullet to accelerate something, it would be the microbicides”. Mr. Bill Gates, Bill & Melinda Gates Foundation

31. Microbicides are scientifically achievable, as exemplified by AIDS therapeutics. With leadership, sufficient financial resources, collaborative efforts and product development expertise, women in developing countries could have access to effective microbicides within the next 5 to 7 years. Conclusion

32. For More Information Martin Methot Executive Director, Resource Development and Communications International Partnership for Microbicides Phone: +1-301-608-2221 Email: mmethot@ipm-microbicides.org www.ipm-microbicides.org