The Search for Microbicides: A Promising New Prevention Tool for Women

1. The Search for Microbicides: A Promising New Prevention Tool for Women US Congress, Women’s Policy Inc. Zeda Rosenberg, Sc.D. December 3, 2008

2. Women and Men With HIV in 2007

3. The Face of HIV Is Increasingly… Female Young Married and monogamous A mother World Bank Photo

4. The Face of HIV in the U.S. • Women account for 26% of AIDS cases, more than triple the rate from 20 years ago • Girls account for 57% of new HIV infections among youth ages 13 to 19 AIDS is the leading cause of death for African-American women ages 25 to 34 Washington, D.C.has highest AIDS prevalence in US (2,017 per 100,000) The number of women living with AIDS in Washington, DC increased 76% over past 6 years

5. Microbicides and HIV prevention • Existing HIV prevention options: • Abstinence • (Be) Faithful • Condoms: Male and female • Treatment of sexually transmitted infections • Prevention of mother-to-child transmission • Male circumcision • Post-exposure prophylaxis • Possible new prevention options — in research: • Topical microbicides • Oral prevention pills (PrEP) • HIV vaccines • Other

6. Microbicides: A Human Rights Issue for Women • Microbicides could restore women’s right to self-protection by providing them with a prevention tool • Microbicides will eventually be developed with both contraceptive and non-contraceptive properties — allowing women to bear children while significantly reducing risk of HIV infection

7. Status of Microbicide Development

8. Microbicides • Topical products to prevent HIV transmission • Could be delivered in many forms: Tablet, capsule, film Gel applicator Ring • Ideally safe, effective, low cost, user-friendly

9. Microbicide Efficacy Trials Summary • 9.5 trials completed or stopped • N9, Savvy, CS, Carraguard, PRO 2000 (2%) • All early generation products • 3 trials ongoing • BufferGel, PRO 2000 (0.5%) — early generation • Tenofovir — next generation • 2 trials planned • Tenofovir, Dapivirine — next generation

10. Early Generation Next Generation • First microbicides tested, some still in efficacy trials • Not HIV specific • Gel formulations • To be applied vaginally within a few hours before sex • No concern about potential resistance • Newer products in different stages of preclinical and clinical research • Specific to HIV (ARV-based) • Various forms: gel, ring, film, tablet • Longer duration of action: daily gels, monthly rings, etc. • ARV resistance is a possible issue that needs to be investigated Early & Next Generation Microbicides

11. Microbicides in Product Development Lactin-V NCp7’s GM Biotics (Osel) Free virus BufferGel PRO2000 SPL7013 (VivaGel) RANTES analogs Cyanovirin-N DS003 (BMS 793) DS001 (Merck 167) Maraviroc (Pfizer) DS007 (Merck L’644) Attachment Fusion S-DABO Dapivirine UC781 Tenofovir PC-815 Pyrimidinediones (Samjin) Reverse Transcription Integration Early-generation compounds Protein synthesis and assembly Next-generation compounds Budding Maturation

12. ARV-Based Microbicides in Development * Also being developed in combination

13. Countries Hosting Microbicide Trials • Thailand • Tanzania • Uganda • United States • Zambia • Zimbabwe • Australia • Belgium • Dominican Republic • Kenya • Malawi • South Africa

14. Ethical Guidelines for Clinical Trials • Many studies taking place in developing countries • Community engagement • Monitoring social harms • Informed consent process • Risk reduction counseling • Family planning / condoms • Management of pregnancy • STI screening and treatment • Testing positive at screening • Participants who seroconvert • Treatment for physical harms • Post-trial access to products Guidelines Key issues • UNAIDS/WHO ethical guidelines in HIV prevention trials, 2007 • UNAIDS/AVAC good participatory practices, 2007 • South Africa GCP guidelines, 2006 • IPM ethical guidelines, 2006 • Nuffield Council on Bioethics, 2005 • GCM consensus points, 2005 • CIOMS biomedical guidelines, 2002 • WMA Declaration of Helsinki, 2000 • ICH GCP, 1996

15. Preparing for Access

16. Access Principles • Availability • Accessibility • Acceptability • Affordability

17. The Important Role of PEPFAR PEPFAR and other programs can help by: • Providing treatment for those infected with HIV during trials • Helping to ensure that a microbicide, once developed, is widely available and affordable

18. The Potential of Microbicides

19. Realistic Expectations • Drug development is a long complex process – many products do not succeed, but these efforts help us develop better products

20. Cause for Optimism • New generation of microbicides with highly potent ARVs • Multiple mechanisms of action against HIV • Single drugs or combinations • Longer duration of protection • Multiple formulations to give women more options • Increased focus on adherence • Novel trial designs • Increased support from donors, pharma, scientific, advocacy and local communities

21. Contribution of Microbicides to Global Development • Improvement in health • Local capacity-building • Gender equality • UN Millennium Development Goals

22. Funding

23. Microbicide Donors • Belgium • Canada • Denmark • France • Germany • Ireland • Netherlands • Norway • South Africa • Spain • Sweden • United Kingdom • United States • European Commission • World Bank • UNFPA • Rockefeller Foundation • Gates Foundation

24. U.S. Government Funding for Microbicides * incomplete Source: Alliance for Microbicide Development, 2008 (www.microbicide.org), based on information from CDC, NIH/OAR, and USAID compiled by HIV Vaccines and Microbicides Tracking Working Group (www.hivresourcetracking.org)

25. Cost and Financial Gap In 2007, the total global investment in microbicide research & development was approximately US$226.5 million The microbicide field estimated in 2006 that $280 million would be needed in each of the subsequent five years to accelerate product development at the necessary levels

26. Leadership and Political Will

27. “No matter where a woman lives, who she is, or what she does, a woman should never need her partner’s permission to save her life.” Women Urgently Need Microbicides BILL GATES, 2006

28. Leadership in Support of Microbicides The growing excitement around a microbicide is entirely warranted. This is a preventive technology whose time has come… it would appear that where preventive technologies are concerned, the microbicide is first in line – Stephen Lewis Our foundation is now partnering with the International Partnership for Microbicides to help accelerate their work by guaranteeing proper care and treatment for all the participants in the test trials– Bill Clinton We want to call on everyone … to help speed up what we hope will be the next big breakthrough on the fight against AIDS - the discovery of a microbicide or an oral prevention drug ... – Bill Gates We believe the most promising breakthrough that could be available soon is an effective microbicide or oral prevention drug – Melinda Gates We are so close (to a microbicide) at this point that the question everybody is asking is no longer if, but when ... and the moment can't come too soon – Sen. Barack Obama