1. When Will Women Have Choices? Sharon Hillier University of Pittsburgh School and Medicine Microbicide Trials Network IAS, Washington DC, July 26, 2012

2. Overview  What is choice are what are options?  Male and female barriers  When will topical microbicide products go to the FDA for registration?  What are the next generation products?

3. What is Choice?  Choice is rational, and can be in opposition to desire. What distinguishes choice is that before a choice is made there is a rational deliberation or thinking things through

4. What is an Option?  The power or freedom to choose Many women may choose to use an HIV prevention method but it may not be an option for them because they do not have the power or freedom to make that choice

5.  Many people just don’t like them  Reduces sensation  Lack of spontaneity  Lack of partner cooperation  Requires male erection  Requires withdrawal after ejaculation  Contraceptive  Embarrassment  Implies mistrust  Loss of intimacy  Relationship-specific So Why Not Male Condoms?

6. Female Barriers and Female Condoms  Diaphragms Randomized trial showed diaphragms not effective for prevention of HIV  Female Condoms Polyurethane More expensive than male condoms Large, nondiscreet Do not require an erect penis No clinical trials demonstrating their effectiveness for prevention of HIV

7. What We Have Learned about Barriers  Sometimes women can make the choice to have their partner use a male condom, but it is not an option for them because they cannot negotiate condom use, they want to become pregnant or they do not like the lack of intimacy  Many women choose not to use female condoms even when they are offered

8. Why Microbicides?  Discretion and control: women can take pills or use gel products under their own control  Nondisruptive: use of the products can be several hours in advance of sexual activity  Noncontraceptive: allows conception for women who desire it

9. Contraceptives: Many Choices

10. But every choice is not an option….  For many women, a contraceptive method might be licensed and might be a woman’s first choice but their insurance will not cover it  In many countries, the family planning programs only stock oral contraceptives and Depo Provera  A better range of options improves uptake and use

11. So How Do We Increase Choice for HIV Prevention in Women?  We have to have products which women choose to use in our clinical trials Only 50% of women enrolled in MTN-001 chose to take their tablets or use their gel daily Only 40% of women enrolled in CAPRISA-004 had 80% adherence to gel product  Vaginal rings which can be inserted once every month (dapivirine ring) or every 3 months (tenofovir ring in development) will make it easier to use prevention

12. 123412341234123412341234 20102011 2012 2013 2014 2015 ARV-based HIV Prevention Timeline * ** As of February 2012 MTN 017 Rectal TFV gel * Trial end-dates are estimates; due to the nature of clinical trials the actual dates may change. For full trial details, see www.avac.org/trials. ** Not all trials included are effectiveness trials. Trials included on this list are mainly phase II/IIb, III/IIIb and IV trials. VOICE/MTN 003 FACTS 001 FACTS 002 (adolescents) CAPRISA 004 CAPRISA 008 Earliest regulatory submission TFV gel Positive efficacy result Arm stopped Regulatory submission/filing DPV ring Oral TDF/FTC Oral TDF Rectal TFV gel TFV gel Planned US FDA filing and decision Oral TDF/ FTC Oral TDF FEM-PrEP TDF2/CDC 4940 TDF2 Open-Label Extension 2007 2009 2007 2009 The Ring Study/IPM 027 DPV ring Earliest regulatory submission ASPIRE/MTN 020 Final results pending iPrEx iPrEx Open-Label Extension (OLE) 2007 2008 Partners PrEP Partners PrEP (no placebo) Bangkok Tenofovir Study/CDC 4370 2005 VOICE/MTN 003 2009

13. Coital Use of Tenofovir for Women FACTS 001 designed as a confirmatory study of CAPRISA 004. Study is testing before and after sex dosing of 1% tenofovir gel in 18-30 year old South African women 2900 women enrolling at 9 sites in South Africa. About 1400 women enrolled now Will support licensure data for FDA licensure for coital use of tenofovir

14. First Generation Rings

15. FDA Approval of PrEP  FDA Advisory Committee May 10, 2012 evaluated the supplemental NDA for Truvada Approval granted earlier this week for prevention of sexual transmission of HIV based on results of iPrEx and Partners PrEP  FACTS-001 tenofovir gel study still ongoing for use of gel product before and after sex; regulatory filing in 2015  Dapivirine ring FDA filing anticipated for 2015

16. Next Generation Rings Courtesy D. Friend, CONRAD and J. Manning, USAID HIV, STI, Contraception TNF/LNG 90 day IVR (CONRAD) HIV, HSV, pregnancy protection Segmented design; co-extruded reservoir LNG segment Sheep vaginal tissue: > 1% TFV gel over 90 days; Target trial date: Q4, 2012 TNF LNG HIV, Contraception Dapivirine + HC Vaginal Ring (IPM) 60 day use Preclinical formulation ongoing

17. Take Home Lessons  We need to HIV prevention products which women want (and that they will choose to use)  Data from completed and ongoing studies have shown that many women do not choose to use oral tablets or gels even when they are available  A greater range of prevention options will increase uptake and use of products

18. The Road Ahead: Choice  The time will come when a woman will be able to choose from among different methods the one that is just right for her