When Will Women Have Choices?

Sharon HillierUniversity 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

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?

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

1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 42010 2011 2012 2013 2014 2015

ARV-based HIV Prevention Timeline * **As of February 2012

MTN 017Rectal 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 resultArm stoppedRegulatory submission/filing

DPV ring

Oral TDF/FTCOral 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 Extension2007

2009

2007

2009

The Ring Study/IPM 027 DPV ring

Earliest regulatory submission

ASPIRE/MTN 020

Final results pendingiPrEx iPrEx Open-Label Extension (OLE)2007

2008 Partners PrEP Partners PrEP (no placebo)

Bangkok Tenofovir Study/CDC 43702005

VOICE/MTN 0032009

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 datafor FDA licensure forcoital 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

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 TFV LNG TNF LNG

• HIV, Contraception• Dapivirine + HC Vaginal Ring (IPM)

• 60 day use• Preclinical formulation ongoing

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