HIV Prevention Options for Women: Microbicides

Martin MethotAugust 10, 2006

International Partnership for MicrobicidesInternational Partnership for Microbicides

Outline of PresentationOutline of PresentationOutline of PresentationOutline of Presentation

The Face of HIV GloballyThe Face of HIV Globally

What is a Microbicide?What is a Microbicide?

International Partnership for International Partnership for Microbicides (IPM)Microbicides (IPM)

Quotes from leaders in the Quotes from leaders in the HIV/AIDS fieldHIV/AIDS field

The Face of HIV GloballyThe Face of HIV GloballyThe Face of HIV GloballyThe Face of HIV Globally

• Increasingly femaleIncreasingly female

• In Sub-Saharan Africa, 74% of young people (aged 15-24 years) living with HIV are female

• In Asia, 30% of all adults living with HIV are female (and new cases are occurring faster in women)

• Female HIV infections are also on the rise in Eastern Europe and Latin America

• In South Africa – 1 in 4 women infected by age 22

• Married, monogamousMarried, monogamous

• In India – 22% of cases in housewives with single partner

• MothersMothers

World Bank Photos

Current HIV Prevention Current HIV Prevention StrategiesStrategies

Current HIV Prevention Current HIV Prevention StrategiesStrategies

Abstinence

Delay first sexual act

Be faithful

Male and female condoms

Behavior change

Treatment of sexually transmitted infections

Other Prevention Strategies Other Prevention Strategies Under ResearchUnder Research

Other Prevention Strategies Other Prevention Strategies Under ResearchUnder Research

Male circumcision

Cervical barriers (diaphragm)

Pre-exposure prophylaxis with ARVs

Herpes suppression

HIV Vaccines

Marriage and Motherhood Marriage and Motherhood as Risk Factorsas Risk Factors

Marriage and Motherhood Marriage and Motherhood as Risk Factorsas Risk Factors

Marriage and women’s own fidelity not enough to protect them against HIV infection

Many women infected, despite staying faithful to one partner: 66% of women surveyed in Zimbabwe and South Africa reported one lifetime partner – and 40% were HIV positive

According to the UN: 56% of pregnant women between 25 and 29 in Swaziland HIV positive – the highest prevalence in 5 years

Women’s VulnerabilityWomen’s VulnerabilityWomen’s VulnerabilityWomen’s Vulnerability

Women's susceptibility to HIV infection results from a combination of biological, social and

cultural factors

Young women are at highest risk of HIV infection due to: an immature physiology

inequitable gender norms – climate that accepts exploitation and violence towards girls

prevalence of transactional sex, coupled with liaisons and marriages between girls and older, more sexually experienced men

The Need for HIV Prevention The Need for HIV Prevention Initiated by WomenInitiated by Women

The Need for HIV Prevention The Need for HIV Prevention Initiated by WomenInitiated by Women

Most HIV infections are spread by unprotected sex

Most current methods are male-initiated and contraceptive

Women have no means to protect themselves if their partners do not use male condoms or allow female condoms

Abstinence and being faithful are not likely to protect married women or those who are sexually abused

What is a Microbicide?What is a Microbicide?What is a Microbicide?What is a Microbicide?

Substance that can prevent transmission of HIV when applied to the vagina

Could be made in many forms:

gel or cream

sponge

film

suppository

vaginal ring or diaphragm

The Ideal MicrobicideThe Ideal MicrobicideThe Ideal MicrobicideThe Ideal Microbicide

Safe - must have no localized toxicity

Effective - must have a significant degree of efficacy in routine use

Cheap - pricing strategy must optimize distribution and availability

User-friendly - must be compatible with use during sex, and acceptable to women and their partners

Robin Shattock, St George’s, University of London

Delivery MethodsDelivery MethodsDelivery MethodsDelivery Methods

Vaginal applicator (right) and

applicators being filled (above)

Vaginal ring (above)

Comprehensive Approaches to HIV/AIDSComprehensive Approaches to HIV/AIDS

Vaccines

Pre-exposureprophylaxis

STI treatment

Male and femalecondoms

Anti-retroviraltherapies(mother-to-child)

Microbicides

Anti-retroviraltherapies

Opportunisticinfectiontherapies

Basic care

Microbicides offer a woman-initiated methodto reduce HIV transmission

Behavior change

Prior to Exposure Point of Transmission

Prevention

Time ofExposure

Prior toExposure

Treatmentand Care

First Generation MicrobicidesFirst Generation MicrobicidesFirst Generation MicrobicidesFirst Generation Microbicides

Products that form physical barriers to HIV or change the chemistry of the vagina to boost up defenses against HIV

In most advanced stage of clinical trials

But likely to be only partially effective

Candidate Microbicide

Mechanism of Action

Sponsor/Funder Trial Location

Carraguard Entry Inhibitor Population Council/Gates, USAID

South Africa – Gugulethu, Isipingo, Durban, Gorankuwa, Shoshanguve

Cellulose SulfateTrial 1

Entry Inhibitor Global Microbicide Program/Gates, USAID

Nigeria – Port Harcourt, Lagos

Cellulose SulfateTrial 2

Entry Inhibitor Global Microbicide Program/Gates, USAID

Burkina Faso, UgandaIndia, KenyaSouth Africa

PRO 2000 Entry Inhibitor UK Medical Research Council/DFID

South Africa – Mtubatuba, Durban, JohannesburgUganda – Masaka Tanzania – Mwanza

PRO 2000Buffer Gel

Entry InhibitorVaginal Defense Enhancer

NIH/NIAID Zimbabwe – Harare, ChitungwizaZambia – Lusaka Malawi – Blantyre, Lilongwe South Africa – Durban, Hlabisa

SAVVY (C31G) Membrane Disruptive Agent (Surfactant)

CONRAD/FHI/USAID Nigeria – Lagos, Ibadan

Current Clinical Efficacy TrialsCurrent Clinical Efficacy TrialsCurrent Clinical Efficacy TrialsCurrent Clinical Efficacy Trials

Next Generation MicrobicidesNext Generation MicrobicidesNext Generation MicrobicidesNext Generation Microbicides

Next generation microbicides Specifically active against HIV Include microbicides that use antiretroviral drugs Examples: Tenofovir/PMPA gel,

Dapivirine/TMC120 gel, UC-781 In safety trials in humans Highly active, can be formulated for slow release

Future of microbicides is likely in combinations Two or more mechanisms of action included in

one product to increase effectiveness

AIDS Therapy TimelineAIDS Therapy TimelineAIDS Therapy TimelineAIDS Therapy TimelineYear Event Description

1981 First documented AIDS case reported in the US

Within 4 years, at least one case of HIV has been reported in each region of the world

1983 HIV virus identified AIDS caused by a retrovirus: Human Immunodeficiency Virus

1987 AZT mono-therapy approved for use

A nucleoside reverse transcriptase (RT) inhibitor, AZT is the first drug to slow the progression of the disease; but not a cure or an easy solution (strict every-4-hour regimen, serious side effects, only offered in advanced stages of the disease)

1995 Two-drug therapy becomes available

FDA approves Invirase, the first protease inhibitor (PI), for use in combination with other nucleoside analogue medications

1997 Three-drug therapy: HAART

Triple-drug combinations proved to be the most effective in suppressing HIV and preventing resistance; Within one year, this highly active antiretroviral therapy (HAART) reduced new AIDS conditions, hospitalizations, and deaths by 80%. First NNRTI type drug, Nevirapine, also becomes available for use

2003 Focus on combinations & reducing pill burden

FDA approves a fourth class of drugs known as fusion inhibitors (FI), in addition to other 1st and 2nd class drugs; Dosing regimen is simplified from 5 to 2 pills a day, then further to 1 pill daily

2006 26 FDA-approved drugs & research continues

Current research works to develop more potent therapies that have fewer toxic effects and are easier to administer (e.g. cellular metabolism modulators, gene therapy, coreceptors, etc.)

Houston, USA

Pittsburgh, USA

Providence, USA

Norfolk, USA

New York, USA

New Brunswick, USA

Baltimore, USA

Santo Domingo, Dominican Republic

Los Angeles, USA

Seattle, USA

London, UK

Antwerp, Belgium

Quebec, Canada

Durban, South Africa

Blantyre, Malawi

Chicago, USA

Birmingham, USA

Florida, USA

Harare, Zimbabwe Lusaka, Zambia

Accra, Ghana

Moshi, Tanzania

Kenya

Johannesburg, South Africa

Pune, India

Chiang Mai, Thailand

Vienna, Austria

Adelaide, Australia

Cincinnati, USA

Kampala, Uganda

Chandigarh, India

Lagos, Nigeria Cameroon

Burkina Faso

Source: Alliance for Microbicide Development

Microbicide Trial SitesMicrobicide Trial SitesMicrobicide Trial SitesMicrobicide Trial Sites

Ethics of HIV Prevention Ethics of HIV Prevention TrialsTrials

Ethics of HIV Prevention Ethics of HIV Prevention TrialsTrials

Informed consent

Family planning counseling

Pre/Post HIV-testing counseling

Referrals for those screening positive

Treatment of STIs

Treatment of those who become HIV-infected during the trial

Treatment of adverse reactions

Resistance

Urgency and AccessUrgency and AccessUrgency and AccessUrgency and Access

Historically, it can take decades for scientific innovation to reach the developing world

The microbicide field is committed to speeding up availability of effective products - reaching those who are most in need first

Microbicides must be widely available and affordable

Key ChallengesKey ChallengesKey ChallengesKey Challenges

Expand pipeline of promising compounds

Promote community engagement at trial sites to ensure community and national ownership

Significantly increase funding for microbicide research and development

Encourage international leaders to support microbicides as part of a comprehensive response to HIV/AIDS

Funding for Microbicide FieldFunding for Microbicide FieldFunding for Microbicide FieldFunding for Microbicide Field

Cost and Financial GapCost and Financial GapCost and Financial GapCost and Financial Gap

In 2005 the global community spent just over $160 million for microbicide research and development.

Funding for the microbicide field needs to double to nearly $300 million annually to accelerate product development.

IPM MissionIPM MissionIPM MissionIPM Mission

IPM’s mission is to prevent HIV transmission by accelerating the development and availability of safe and effective microbicides for use by women in developing countries.

Opportunities For ActionOpportunities For ActionOpportunities For ActionOpportunities For Action

1. Assess and fundacross the microbicide

portfolio

4. Optimize clinical trialcapacity

2. Help develop the“next generation”of microbicides

3. Provide commoncapabilities or

supports for the field

Coordinate effortto ensure widespread

availability and adoption

DiscoveryBasic

researchPre-

clinicalClinical

trials Launch

Multiple mechanisms/targets/products

Formulation capacityIn vitro and in vivo modelsRegulatoryManufacturing

Pharmaceutical PartnersPharmaceutical PartnersPharmaceutical PartnersPharmaceutical Partners

IPM in-licensed compounds from three large pharmaceutical companies:

TMC120 or Dapivirine - from Tibotec Pharmaceuticals/ Johnson & Johnson

M167 - from Merck & Co.

BMS793 - from Bristol-Myers Squibb

Royalty-free rights to develop, manufacture and distribute microbicides in developing countries

IPM Clinical Trials: IPM Clinical Trials: TMC120 SafetyTMC120 Safety

IPM Clinical Trials: IPM Clinical Trials: TMC120 SafetyTMC120 Safety

First use in Africa

Expanded safety (42 days use, 112 women)

Sites: Kigali, Rwanda (with Project Ubuzima) Moshi, Tanzania (with KCMC & Harvard) Johannesburg, S. Africa (with Univ. of Witwatersrand) Bloemfontein, S. Africa (with FARMVOS-Parexel)

Delivery SystemsDelivery SystemsDelivery SystemsDelivery Systems

The delivery vehicle for an active drug is just as critical as the active itself.

Semisolids: gels (including once-a-day gels), creams, lotions, emulsions

Develop “non-coitally dependent” microbicides and vehicles allowing for slow release: vaginal rings

Leaders SpeakLeaders SpeakLeaders SpeakLeaders Speak

“Quite frankly, I find it extraordinary that the search for an effective and safe vaginal microbicide has been progressing so slowly. Particularly as we know that microbicides are a real possibility.” 

Dr. Peter Piot, Dr. Peter Piot,

Executive Director, UNAIDSExecutive Director, UNAIDS

“Quite frankly, I find it extraordinary that the search for an effective and safe vaginal microbicide has been progressing so slowly. Particularly as we know that microbicides are a real possibility.” 

Dr. Peter Piot, Dr. Peter Piot,

Executive Director, UNAIDSExecutive Director, UNAIDS

“The women of Africa need new prevention options. They are at tremendous risk for HIV, so they should be empowered with an option to reverse the pandemic. Microbicides will put HIV-prevention into their hands”.

Mrs. GraMrs. Graçça Machel, President, a Machel, President,

Foundation for Community Development, MozambiqueFoundation for Community Development, Mozambique

“The women of Africa need new prevention options. They are at tremendous risk for HIV, so they should be empowered with an option to reverse the pandemic. Microbicides will put HIV-prevention into their hands”.

Mrs. GraMrs. Graçça Machel, President, a Machel, President,

Foundation for Community Development, MozambiqueFoundation for Community Development, Mozambique

Leaders Speak (cont.)Leaders Speak (cont.)Leaders Speak (cont.)Leaders Speak (cont.)

“Making microbicides available, accessible and affordable for women is one of the greatest and most significant contributions the world can make for women to protect themselves from HIV infection”.

Ms. Anandi Yuvaraj, Ms. Anandi Yuvaraj,

India HIV/AIDS AllianceIndia HIV/AIDS Alliance

“Making microbicides available, accessible and affordable for women is one of the greatest and most significant contributions the world can make for women to protect themselves from HIV infection”.

Ms. Anandi Yuvaraj, Ms. Anandi Yuvaraj,

India HIV/AIDS AllianceIndia HIV/AIDS Alliance

“ Gender inequality is driving the virus, and that is why the microbicide potential is perhaps in the immediate future the most significant potential of all”.

Mr. Stephen Lewis, Mr. Stephen Lewis,

U.N. Special Envoy for HIV/AIDS in AfricaU.N. Special Envoy for HIV/AIDS in Africa

“ Gender inequality is driving the virus, and that is why the microbicide potential is perhaps in the immediate future the most significant potential of all”.

Mr. Stephen Lewis, Mr. Stephen Lewis,

U.N. Special Envoy for HIV/AIDS in AfricaU.N. Special Envoy for HIV/AIDS in Africa

Leaders Speak (cont.)Leaders Speak (cont.)Leaders Speak (cont.)Leaders Speak (cont.)

“If we’re going to end AIDS, we have to keep working on vaccines, microbicides and other prevention strategies”.

Mr. Bill Clinton,Mr. Bill Clinton,

The Clinton FoundationThe Clinton Foundation

“If we’re going to end AIDS, we have to keep working on vaccines, microbicides and other prevention strategies”.

Mr. Bill Clinton,Mr. Bill Clinton,

The Clinton FoundationThe Clinton Foundation

“If I had a magic bullet to accelerate something, it would be the microbicides”.

Mr. Bill Gates, Mr. Bill Gates,

Bill & Melinda Gates FoundationBill & Melinda Gates Foundation

“If I had a magic bullet to accelerate something, it would be the microbicides”.

Mr. Bill Gates, Mr. Bill Gates,

Bill & Melinda Gates FoundationBill & Melinda Gates Foundation

ConclusionConclusionConclusionConclusion

Microbicides are scientifically achievable, as exemplified by AIDS therapeutics.

With leadership, sufficient financial resources, collaborative efforts and product development expertise, women in developing countries could have access to effective microbicides within the next 5 to 7 years.

For More InformationFor More InformationFor More InformationFor More Information

Martin Methot

Executive Director,

Resource Development and Communications

International Partnership for Microbicides

Phone: +1-301-608-2221

Email: mmethot@ipm-microbicides.org

www.ipm-microbicides.org