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

Women and Men With HIV in 2007

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

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

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

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

Status of Microbicide Development

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

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 Microbicide Efficacy Trials Summary

Early & Next Generation Microbicides  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  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 Next Generation Early Generation

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

ARV-Based Microbicides in Development ClassDrugDeveloperDevelopment Stage NNRTIDapivirine * UC-781 * PC-815 Pyrimidinediones S-DABO IPM CONRAD Population Council ImQuest Idenix Phase 1/2 Phase 1 Preclinical NRTITenofovir *IPM / CONRADPhase 1/2B CCR5 blockerMaraviroc * Merck L-167, 872, 882 RANTES analogs IPM Mintaka Foundation Preclinical gp41 binderMerck L-644IPMPreclinical gp120 binderBMS-793 Cyanovirin-N IPM Osel Preclinical Zinc finger inhibitor NCp7’sImQuestPreclinical * Also being developed in combination

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

Ethical Guidelines for Clinical Trials  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 Many studies taking place in developing countries 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 Guidelines

Preparing for Access

Access Principles Availability Accessibility Acceptability Affordability

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

The Potential of Microbicides

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

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

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

FundingFunding

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

U.S. Government Funding for Microbicides * incomplete Source: Alliance for Microbicide Development, 2008 ( based on information from CDC, NIH/OAR, and USAID compiled by HIV Vaccines and Microbicides Tracking Working Group ( FY 2004FY 2005FY 2006FY 2007FY 2008 Actual NIH Total66,38866,68488,29798,700115,000 CDC4,0005,1851,8361,490ND Subtotal HHS 70,38871,86990,133100,190115,000* USAID21,87029,76039,600 ND FEDERAL TOTAL 92,258101,629129,733139,790115,000*

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

Leadership and Political Will

Women Urgently Need Microbicides “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.” BILL GATES, 2006

Leadership in Support of Microbicides 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 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 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