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Microbicide Research: A Promising HIV/AIDS Prevention Strategy for Women

DHHS/NIH/NIAID. Microbicide Research: A Promising HIV/AIDS Prevention Strategy for Women. Roberta Black, Ph.D. Division of AIDS, National Institute of Allergy and Infectious Diseases National Institutes of Health December 3, 2008.

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Microbicide Research: A Promising HIV/AIDS Prevention Strategy for Women

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  1. DHHS/NIH/NIAID Microbicide Research: A Promising HIV/AIDS Prevention Strategy for Women Roberta Black, Ph.D. Division of AIDS, National Institute of Allergy and Infectious Diseases National Institutes of Health December 3, 2008

  2. Combination disease prevention product, e.g., HIV + HSV microbicide DHHS/NIH/NIAID Microbicide ProductsPurposes and Indications Singular indication product, e.g., HIV microbicide Combination sexual and reproductive health product, e.g., HIV microbicide + contraceptive

  3. Progression to AIDS o Years Weeks NIAID Topical Microbicide Program Overarching Goal To identify and support/facilitate development of safe, effective and acceptable topical microbicides to prevent HIV/AIDS and other STIs Intervention Points for Microbicides in HIV Infection and Disease HIV Negative Individuals HIV Positive Individuals DHHS/NIH/NIAID

  4. The Microbicide Development Pipeline 10,000 cndts 250 5 1 Pilot Studies Preclinical Studies (Critical Path) I III II Preclinical Virology Deployment Discovery Clinical Studies Product recycled In Pipeline Product Recycled Into Discovery Successful Microbicide Or Microbicide Strategy LEAD Lead Identification And Optimization Pipeline Development Multiple activities driven by Milestones that may occur sequentially or simultaneously Product Eliminated DHHS/NIH/NIAID

  5. NIAID Topical Microbicide Program • Basic biomedical research • Foster basic science and preclinical pipeline studies • Nonclinical product development • Identify and advance the most promising approaches to clinical testing • Clinical evaluation • Evaluate safety, efficacy and acceptability in populations most in need Three Areas of Emphasis DHHS/NIH/NIAID

  6. UC781 (Vaginal and Rectal) Virus gp41 gp120 V3 V1/2 CD4 Coreceptor Cell DHHS/NIH/NIAID Basic Biomedical Research • Understand the basic biologic processes of the female reproductive tract and its interaction with seminal plasma • Define mechanisms of infection • Identify targets for microbicide discovery • Discover new microbicide candidates • HIV targets • STI targets • Cellular/tissue targets • Understand the interaction of microbicides with the tissues

  7. Behavioral DHHS/NIH/NIAID Non-Clinical Product Development • Identify and help advance the most promising approaches to clinical testing • Feasibility –compatible with use as a microbicide? • Proof-of-concept –prevent HIV transmission in vitro and/or in vivo? • Develop and use relevant and predictive in vitro and in vivo safety, efficacy and adherence models to select the best candidates • Establish partnerships/collaborations among private sector, industry and NGOs with NIH and its grantees • Encourage and promote the integration of new expertise and technologies into the microbicide pipeline Endometrial Toxicity

  8. Combination Inhibitors 4th Generation Microbicide Evolution Nonoxynol-9 1st Generation Nonspecific inhibitors 2nd Generation HIV specific inhibitors 3rd Generation • NRT • NNRT • CCR5 DHHS/NIH/NIAID

  9. DHHS/NIH/NIAID HPTN 035: Phase II/IIb Trial of Vaginal Microbicides for the Prevention of HIV Infection in WomenSUMMARY • Primary Objectives: • To evaluate the safety of BufferGel and 0.5% PRO 2000/5 Gel (P) when applied intravaginally by women at risk for sexually-transmitted HIV infection. • To estimate the effectiveness of these gels in preventing HIV infection. • Design: A phase II/IIb, four-arm, multisite, randomized, controlled, trial comparing BufferGel and 0.5% PRO 2000/5 Gel (P) with a placebo gel and with no treatment (condom only arm). • Population:Sexually active HIV-uninfected women • Sample Size:3100 participants • Countries:Malawi, South Africa, USA, Zambia, Zimbabwe

  10. DHHS/NIH/NIAID HPTN 035: Phase II/IIb Trial of Vaginal Microbicides for the Prevention of HIV Infection in WomenSTATUS • Trial initiated in February 2005 • Enrollment and follow up complete • Data analysis ongoing • Results expected February 2009

  11. MTN-003:The VOICE Study Vaginal and Oral Interventions to Control the Epidemic • Phase 2B, Safety and Effectiveness Study • 1% Tenofovir (PMPA) Gel • Tenofovir DF (TDF) Tablet • TDF/FTC (emtricitabine) Tablet

  12. MTN-003: The VOICE Study

  13. Why a Head-to-Head Trial? • Theoretical reasons to favor either approach for safety, acceptability, efficacy and/or selection of resistance • vaginal use may confer less systemic toxicity and less resistance • vaginal use may be more culturally acceptable • oral use is less closely linked to sexual practices, and can be administered by the woman without knowledge of her partner • NO HUMAN DATA • Only head-to-head trial will answer questions

  14. PMPA Gel: Following a Classic Drug Development Paradigm 2006 2007 2008 HPTN 050 Phase I Safety HPTN 059 Phase II Expanded Safety Male Tolerance Tissue PK MTN-002 Pregnancy MTN-001 Oral vs. Topical PK MTN-003 VOICE STUDY

  15. Optical Coherence Tomography (OCT) DHHS/NIH/NIAID Additional Priority Areas • Discovery and development of new basic and preclinical science and concepts required to support/enhance microbicide clinical trials • Safety • Microbicides for prevention of other STIs • Associated with enhancement of HIV transmission • Microbicides for use during pregnancy • Increased susceptibility of pregnant women • Tools for measuring adherence and acceptability

  16. DHHS/NIH/NIAID Additional Priority Areas • Discovery and development of new basic and preclinical science and concepts required to support/enhance microbicide clinical trials • Safety • Microbicides for prevention of other STIs • Associated with enhancement of HIV transmission • Microbicides for use during pregnancy • Increased susceptibility of pregnant women • Tools for measuring adherence and acceptability

  17. DHHS/NIH/NIAID How does NIAID make this all happen? • Grants • Unsolicited Grants • Specific Initiatives 2. Contracts • Microbicide-specific product advancement • Gap-filling resources for nonclinical development 3. Partnerships

  18. Controlling the HIV Pandemic Anti-Retroviral Therapy Prevention Microbicides HIV Other STIs Combinations Perinatal Mother-to-child Transmission (MTCT) DHHS/NIH/NIAID Vaccines HIV Other STIs STI Reduction HSV-2 Antiretroviral Therapy Pre-exposure Prophylaxis (PrEP) Intervention Strategies Risk reduction Voluntary counseling (VCT) Ultimate Goal: Multi-Component Prevention Strategy

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