When Will Women Have Choices?

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

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?

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

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

So Why Not Male Condoms? • 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

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

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

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

Contraceptives: Many Choices

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

So How Do We Increase Choice forHIV 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

ARV-based HIV Prevention Timeline ***As of February 2012 2015 2012 2014 2010 2011 2013 Bangkok Tenofovir Study/CDC 4370 2005 Oral TDF CAPRISA 004 CAPRISA 008 Partners PrEP Partners PrEP (no placebo) 2008 VOICE/MTN 003 2009 Oral TDF/ FTC iPrEx Open-Label Extension (OLE) 2007 TDF2 Open-Label Extension TDF2/CDC 4940 2007 Final results pending Rectal TFV gel FEM-PrEP 2009 MTN 017 US FDA filing and decision Positive efficacy result 2007 Arm stopped 2009 Regulatory submission/filing VOICE/MTN 003 TFV gel iPrEx Planned FACTS 001 FACTS 002 (adolescents) Earliest regulatory submission Oral TDF Oral TDF/FTC TFV gel Earliest regulatory submission Rectal TFV gel The Ring Study/IPM 027 DPV ring DPV ring ASPIRE/MTN 020 * 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.

Coital Use of Tenofovir for Women • FACTS 001 designed as a confirmatorystudy 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

First Generation Rings

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

Next Generation Rings • HIV, Contraception • Dapivirine + HC Vaginal Ring (IPM) • 60 day use • Preclinical formulation ongoing • 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 Courtesy D. Friend, CONRAD and J. Manning, USAID

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

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

When Will Women Have Choices?