International Partnership for Microbicides

HIV Prevention Options for Women: Microbicides

Martin Methot
August 10, 2006
Outline of Presentation

 The Face of HIV Globally

 What is a Microbicide?
 International Partnership for
Microbicides (IPM)
 Quotes from leaders in the
HIV/AIDS field
 The Face of HIV Globally

• Increasingly 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
World Bank Photos
Eastern Europe and Latin America
• In South Africa – 1 in 4 women infected by age 22

• Married, monogamous
• In India – 22% of cases in housewives with
single partner
• Mothers
 Current HIV Prevention
Strategies
 Abstinence
 Delay first sexual act
 Be faithful
 Male and female condoms
 Behavior change
 Treatment of sexually transmitted infections
Other Prevention Strategies
Under Research
 Male circumcision

 Cervical barriers (diaphragm)

 Pre-exposure prophylaxis with ARVs

 Herpes suppression

 HIV Vaccines
 Marriage and Motherhood
as 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 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
Initiated 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?
 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 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 Methods

Vaginal ring
(above)

Vaginal applicator
(right) and
applicators being
filled (above)
Comprehensive Approaches to HIV/AIDS
Prevention
Treatment
Prior to Time of and Care
Exposure
Prior to Exposure Exposure
Point of Transmission

Vaccines Male and female Anti-retroviral

condoms therapies
Pre-exposure
prophylaxis
Anti-retroviral Opportunistic
STI treatment therapies infection
(mother-to-child) therapies
Behavior change

Basic care
Microbicides
Microbicides offer a woman-initiated method
to reduce HIV transmission
First 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

Current Clinical Efficacy Trials
Candidate Mechanism of Sponsor/Funder Trial Location
Microbicide Action
Carraguard Entry Inhibitor Population South Africa – Gugulethu,
Council/Gates, USAID Isipingo, Durban, Gorankuwa,
Shoshanguve
Cellulose Sulfate Entry Inhibitor Global Microbicide Nigeria – Port Harcourt, Lagos
Trial 1 Program/Gates, USAID
Cellulose Sulfate Entry Inhibitor Global Microbicide Burkina Faso, Uganda
Trial 2 Program/Gates, USAID India, Kenya
South Africa
PRO 2000 Entry Inhibitor UK Medical Research South Africa – Mtubatuba,
Council/DFID Durban, Johannesburg
Uganda – Masaka
Tanzania – Mwanza
PRO 2000 Entry Inhibitor NIH/NIAID Zimbabwe – Harare,
Buffer Gel Vaginal Defense Chitungwiza
Enhancer Zambia – Lusaka
Malawi – Blantyre, Lilongwe
South Africa – Durban, Hlabisa
SAVVY (C31G) Membrane CONRAD/FHI/USAID Nigeria – Lagos, Ibadan
Disruptive Agent
(Surfactant)
Next 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 Timeline
Year Event Description
1981 First documented AIDS Within 4 years, at least one case of HIV has been reported in
case reported in the US each region of the world
1983 HIV virus identified AIDS caused by a retrovirus: Human Immunodeficiency Virus
1987 AZT mono-therapy A nucleoside reverse transcriptase (RT) inhibitor, AZT is the
approved for use 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 FDA approves Invirase, the first protease inhibitor (PI), for use
becomes available in combination with other nucleoside analogue medications
1997 Three-drug therapy: Triple-drug combinations proved to be the most effective in
HAART 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 FDA approves a fourth class of drugs known as fusion
& reducing pill burden 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 Current research works to develop more potent therapies that
& research continues have fewer toxic effects and are easier to administer (e.g.
cellular metabolism modulators, gene therapy, coreceptors,
etc.)
 Microbicide Trial Sites

Vienna, Austria
Quebec, Canada Antwerp, Belgium
London, UK

New York, USA

Cincinnati, USA
Seattle, USA Providence, USA
New Brunswick, USA
Los Angeles, USA Pittsburgh, USA
Baltimore, USA
Chicago, USA Norfolk, USA Chandigarh, India
Houston, USA
Birmingham, USA
Pune, India Chiang Mai, Thailand
Florida, USA Burkina Faso
Accra, Ghana Kenya
Santo Domingo,
Dominican Republic Kampala, Uganda
Moshi, Tanzania
Lagos, Nigeria
Cameroon Blantyre, Malawi
Harare, Zimbabwe
Lusaka, Zambia
Johannesburg, South Africa
Durban, South Africa
Adelaide, Australia

Source: Alliance for Microbicide Development

Ethics of HIV Prevention
Trials
 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 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 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 Field
 Cost 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 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 Action
1. Assess and fund Coordinate effort 4. Optimize clinical trial
across the microbicide to ensure widespread capacity
portfolio availability and adoption

Basic Pre- Clinical

Discovery Launch
research clinical trials

3. Provide common
2. Help develop the capabilities or
“next generation” supports for the field
of microbicides

Formulation capacity
Multiple mechanisms/ In vitro and in vivo models
targets/products Regulatory
Manufacturing
 Pharmaceutical 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:
TMC120 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 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 Speak

“Quite
“Quitefrankly,
frankly,I Ifind
findititextraordinary
extraordinarythat
thatthe
thesearch
searchfor
foran
an
effective
effective and safe vaginal microbicide has been progressingso
and safe vaginal microbicide has been progressing so
slowly. Particularly as we know that microbicides are
slowly. Particularly as we know that microbicides are a real a real
possibility.” 
possibility.” 
Dr.
Dr.Peter
PeterPiot,
Piot,
Executive
ExecutiveDirector,
Director,UNAIDS
UNAIDS

“The
“Thewomen
womenofofAfrica
Africaneed
neednew
newprevention
preventionoptions.
options.They
Theyare
are
atattremendous risk for HIV, so they should be empowered
tremendous risk for HIV, so they should be empowered with with
an
anoption
optiontotoreverse
reversethethepandemic.
pandemic.Microbicides
Microbicideswill
willput
putHIV-
HIV-
prevention into their hands”.
prevention into their hands”.

Mrs.
Mrs.Gra
GraççaaMachel,
Machel,President,
President,
Foundation
Foundationfor
forCommunity
CommunityDevelopment,
Development,Mozambique
Mozambique
 Leaders Speak (cont.)

“Making
“Makingmicrobicides
microbicidesavailable,
available,accessible
accessibleand
and
affordable
affordable for women is one of the greatest andmost
for women is one of the greatest and most
significant
significantcontributions
contributionsthe
theworld
worldcan canmake
makefor
forwomen
women
totoprotect themselves from HIV infection”.
protect themselves from HIV infection”.
Ms.
Ms.Anandi
AnandiYuvaraj,
Yuvaraj,
India
IndiaHIV/AIDS
HIV/AIDSAlliance
Alliance

““Gender
Genderinequality
inequalityisisdriving
drivingthe
thevirus,
virus,and
andthat
thatisiswhy
whythe
the
microbicide potential is perhaps in the immediate future
microbicide potential is perhaps in the immediate future the the
most
mostsignificant
significantpotential
potentialofofall”.
all”.

Mr.
Mr.Stephen
StephenLewis,
Lewis,
U.N.
U.N.Special
SpecialEnvoy
Envoyfor
forHIV/AIDS
HIV/AIDSininAfrica
Africa
 Leaders Speak (cont.)

“If
“Ifwe’re
we’regoing
goingtotoend
endAIDS,
AIDS,we
wehave
havetotokeep
keepworking
workingonon
vaccines, microbicides and other prevention strategies”.
vaccines, microbicides and other prevention strategies”.

Mr.
Mr.Bill
BillClinton,
Clinton,
The
TheClinton
ClintonFoundation
Foundation

“If
“IfI Ihad
hadaamagic
magicbullet
bullettotoaccelerate
acceleratesomething,
something,ititwould
would
be the microbicides”.
be the microbicides”.
Mr.
Mr.Bill
BillGates,
Gates,
Bill
Bill&&Melinda
MelindaGates
GatesFoundation
Foundation
 Conclusion

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 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