Transcript Positioning Microbicides

Microbicides
Research:
An Overview
On behalf of the Global Campaign for Microbicides
[email protected]
Overview

The Need
Define microbicides/methods of action

Research overview

Potential impact of microbicides
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How microbicides fit into HIV
prevention
Need for advocacy
“All too often, HIV
prevention is failing
women and girls”
- Dr. Peter Piot
Executive Director, Joint United
Nations Programme on HIV/AIDS
The Global Challenge

HIV is rapidly becoming a “women’s epidemic”
– Worldwide, 6 out of every 10 people newly
infected with HIV are women
- In 2005 17.5 million women were living with HIV;
1 million more than in 2003.
- In Sub-Saharan Africa, 67% of the almost 9
million HIV youth (15-25 years) are female
- In the US, women have gone from less than 10%
to nearly a quarter of new cases (more than a
third of new HIV cases in CT)
- Young girls are three to six times more likely than
their male counterparts to be infected.
Women’s Risk is…

Biological
– Cervical vulnerability; untreated STD

Social
– Couplings with older men and younger
women; rape
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Cultural
– Sanctioned polygamy; institutionalized
ignorance of sex; lack of women’s rights,
economic inequity
Young Women Are
Especially Vulnerable
Numerous physiologic and cognitive
changes in youth strongly influence
STI rates and HIV acquisition among
young women
• Cognitive vulnerability
• Structural vulnerability of the mucosa
• Immunologic vulnerability
• Cultural Vulnerability
Current Prevention Options
for Women
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Abstinence
Trusting Partner to be Uninfected and
Monogamous
Persuading Partners to Use Male
Condoms
Female Condoms
How can we address women’s
disproportionate risk?

Empower women
- Education, economic opportunities, legal
reform

Change gender dynamics
- Work with men, promote non-violence,
egalitarian family relationships

Get women tools to protect themselves
-
female condoms; topical microbicides
Why non-condom
prevention?
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Existing methods -- condoms and mutual
monogamy -- depend upon the cooperation
of a male partner.
Violence, coercion, and economic
dependency in relationships make it hard to
“negotiate” condom use or to leave a
partnership that puts a woman at risk.
Condoms interfere with conception
So, What is a
Microbicide?
Microbicides

Products that reduce the probability of
mucosal transmission of HIV and
possibly other STDs.
– The first generation of microbicides will
likely be topical agents applied in the
vagina, and possibly the rectum.
– Other “delivery devices”, such as slow
release rings are being explored
Microbicides Must Be…

Safe for all potential users:
– Sexually active women and men
– Pregnant women
– HIV positive women
– Adolescents
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Compatible with condoms and other
barriers
Microbicides Must Work:
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In normal situations
Where there is cervical ectopy
In the presence of inflammatory and
ulcerative STDs
In the face of micro trauma due to
intercourse.
To prevent HIV transmission
a microbicide MUST …
either inactivate the virus in the vaginal lumen
or prevent the virus from attaching to and/or fusing
with its cellular targets
or accumulate inside the target cells and prevent viral
replication if the virus manages to enter
or a combination of some or all of these
Microbicides must NOT:
 damage the protective mucosal barrier
 interfere with the vaginal lactobacilli
ALAN STONE
~ LONDON ~
Shattock CROI 04
POTENTIAL PROTECTIVE EFFECTS
OF A MICROBICIDAL GEL
Physicochemical effect of microbicidal ingredient
(inactivates the pathogen or prevents its interaction
with target cell/tissue or blocks its replication)
Anti-infective effect of polymeric gelling agent or
preservative
Low pH formulation hostile to pathogens
Gel forms a physical barrier between pathogen and
target cell/tissue
Gel acts as a lubricant during sex and thus minimises
trauma to mucosa
Ideally all of these
ALAN STONE
~ LONDON ~
the ideal microbicide …
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bi-directional
available over the counter
active against a range of sexuallytransmitted pathogens
long duration of effect
available in spermicidal & nonspermicidal formulations
sustain or enhance normal vaginal
ecology
Alliance for Microbicide Development
Attributes Considered
Shattock CROI 04
•Breadth of activity (phenotype and clade)
•Therapeutic index
•Activity in physiological fluids (semen, mucus, blood)
•Ease of Manufacture
•Ease of Formulation
•Time to Develop
•Regulatory Hurdles
•Stability (40C for 6 months)
•Cost
•“Best in class/better than existing”
•Acceptability
•Resistance Profile
•Safety / Efficacy
Effectiveness Will Be
Determined By:
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Formulation
Acceptability
Distribution
Stability
The Product Pipeline
5 products
2 products
10-20 products
Laboratory
Testing
2-6 Years
10 products
Phase 1
(safety)
Phase 2
(safety)
Phase 3
(efficacy)
1 to 6
Months
Up to 2
Years
2 to 4
Years
25 – 40
people
200-400
people
3,000-10,000
people
Simultaneous studies:
HIV+, penile & rectal
10 or more years
Clinical trial sites in 2005
Quebec, Canada
New York, USA
Cincinnati, USA
Providence, USA
New Brunswick, USA
Seattle, USA
Los Angeles, USA
Chicago, USA
Houston, USA
Birmingham, USA
Vienna, Austria
Antwerp, Belgium
London, UK
Pittsburgh, USA
Baltimore, USA
Norfolk, USA
Chandigarh, India
Pune, India
Florida, USA
Santo Domingo,
Dominican Republic
Burkina Faso
Accra, Ghana
Lagos, Nigeria
Cameroon
Lusaka, Zambia
Chiang Mai, Thailand
Kenya
Kampala, Uganda
Moshi, Tanzania
Blantyre, Malawi
Harare, Zimbabwe
Johannesburg, South Africa
Durban, South Africa
Adelaide, Australia
Source: Alliance for Microbicide Development
Context of Microbicide
Clinical Trials
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Enroll large numbers of
healthy women
Partner exposure to
product
Infections will occur
among some
participants
Participants receive
“gold standard”
prevention
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Products primarily
developed in “western”
countries and tested in
“resource-constrained”
settings
Limited resources for
microbicide trials
Access to treatment
may be limited
Prevention Counseling is a Routine Part of Microbicide
Trials
If Providing Prevention
Counseling and Condoms
Means it Will Take More
Time and Resources to
Discover a Microbicide, Is it
More Ethical to Provide the
Prevention Intervention or
to Hasten Discovery ???
Informed
Consent
Blah Blah
Placebo Blah
Blah Randomize
Blah Blah Blah
Therapeutic Misconception
I’m sure that gel is
protecting me. It is
even giving me more
energy !
That gel is doing
wonders for my
complexion!
I know
that nice
nurse
must be
giving
me the
real gel!
Partner Exposure

Should male partners consent?
– Women could have multiple partners during trial
– What is disempowering effect on women if
partners have to consent?
– Are women placed at increased risk of violence if
partners don’t consent?
– Is it feasible to require partner consent?
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Penile safety studies being conducted in
earlier safety phases of testing
Vulnerable IndividualsAdolescents
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Treated by law as “children” needing special
protection; unable to give fully informed
consent
At high risk of acquiring HIV
Biologically different than adult females
Unique potential benefits and harms
Need to assess safety and efficacy in this
population as they are likely to be signicant
users
How to enroll and protect confidentiality?
Responsibility to SeroConverters
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Women in microbicide trials are likely
at less risk than those not in trials
Condom only
Risk
`
Condoms +
placebo gel
Condoms +
microbicide
Before trial
During Trial
(if it works)
Source: Heise, L.
Improving Local Care
Capacity
New Labs/Clinics
STD Care
Repro Health Care
ARVS for HIV+
Competing Community
Interests
Ethical Obligations
Lack of Country Infrastructure
Treatment Needs After
Study Completion
Budget Constraints
Balancing Responsibilities
to Sero-Converters
5 Products Furthest Along
Buffer Gel
Feb 2005 - 3,220 women
South Africa, Malawi, Tanzania,
Zambia, and Philadelphia
Mar. 2004 - 6,270 women
South Africa – 3 locations
Global Microbicide Project
Oct. 2004 - 2160 women
Mar. 2005 - 2,574 women
Nigeria
Benin, Burkina Faso, India,
Kenya, South Africa, Uganda
PRO 2000 (.5%)
Feb 2005 - 3,220 women
South Africa, Malawi, Tanzania,
Zambia, and Philadelphia
2005 - 11,920 women
South Africa, Uganda, Zambia,
Tanzania
Mar. 2004 - 2,142 women
Ghana and Nigeria
ReProtect LLC
Carraguard
Population Council
Cellulose sulfate
Indevus Pharmaceutical, Inc.
PRO 2000 (.5% and 2%)
Indevus Pharmaceutical, Inc.
Savvy
Biosyn, Inc
How will microbicides and
condoms compare?
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
Early generation products will probably
be less effective than condoms…
But they will more effective than
condoms that aren’t used correctly or
at all.
Prevention Trade-Off
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
A low efficacy method used consistently can
achieve the same protection as a highefficacy method used less consistently
A 90% efficacious method (like condoms)
used in 20% of sex acts, provides less
protection than a:
 70% efficacy used> 30% of the time
 50% efficacy used> 40% of the time
 30% efficacy used> 60% of the time
Watts
How Effective Will
Microbicides Be?
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First microbicides may be 40-60% protective
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Second generation products may be 60-80%
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Should be promoted as an adjunct or “backup” to condoms, not as a replacement
use with harm reduction messages, such as:
– Use a male or female condom every time
you have sex; if you absolutely can’t use a
condom, use a microbicide
– Use a microbicide with your condom for
added pleasure and protection
Potential public health Impact
(Watts et al, 2002)

Introduction of a 60% efficacious microbicide
in 73 lower income countries would avert 2.5
million HIV infections over 3 years (in men,
women & infants)
– assumes microbicide is used by 20% of those
individuals likely to be reached by existing services
– microbicides used in 50% of sex acts where
condoms are not
– assumes 10% migration away from condom
Women newly infected with HIV (2002)
Adult women dying of AIDS (2002)
Watts
2.0 million
2.0 million
Impact is driven by coverage
4.5
3.9
4.5
4.0
3.5
3.5
2.7
3.7
3.0
1.5
1.0
0.5
3.0
2.5
2.5
2.0
4.0
2.5
2.0
1.5
1.5
1.4
1.5
1.0
1.0
0.5
0.6
0.0
Productivity gains and savings to
Health System (billions US$2002)
Cumulative HIV infections
averted (millions)
5.0
0.0
10%
20%
30%
Coverage of groups in contact with services
Total HIV averted
Direct savings to health system
Watts
Present productivity gains
Take Home Messages

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Even a relatively low efficacy microbicide
could have a large impact on the
epidemic
The magnitude of impact is strongly
influenced by coverage and use
Coverage
Infections averted*
10%
1.4 million
20%
2.5 million
30%
3.6 million
Watts
* over 3 years
Microbicides as
Harm Reduction
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
Microbicides fit within a
harm reduction model of
disease prevention
If you are going to be
sexual:
– Use male/female condoms
+ microbicides- if not;
– Use male/female condoms
alone, if not;
– Use a microbicide
What About
“Condom Migration”
?
What About
“Condom Migration”?


Data from contraception studies shows
more methods are better than fewer
Addition of each new method
–
–

increases overall number of protected acts
decreases unintended pregnancies
For HIV risk: modeling suggests that
substantial migration can occur without
increasing rates infection
Changes in condom use and
impact on HIV/STD risk
IF: a microbicide of 50% efficacy were used
in 50% of acts when condoms aren’t used
Condom consistency could decrease
from:
BEFORE
30%
50%
70%
90%
AFTER
5%
32%
59%
86%
without increasing individual risk
Foss, Vickerman, Heise, Watts
Reductions in Condom Consistency
That Could be Tolerated Without
Increasing Risk
Microbicide HIV/STI efficacy = 50%;
Used in 100% of acts not protected by condoms
Condom Consistency
Condom Consistency
BEFORE
30%
50%
70%
90%
AFTER
0%
0%
37%
79%
Foss, Vickerman, Heise, Watts
Will Women Use
Microbicides?
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21.3 million women in the US would be
interested in using a microbicide (Darroch &
Frost, 1999)
Even in resource-poor countries, women at
risk are willing to pay twice as much (or
more) than the local price of a condom (EU
study, 1998; Hardy, et al 1998)
Women have widely different needs and
formulation preferences so multiple products
will be the key to widespread acceptability
and use
What About Rectal
Microbicides?
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Needed by BOTH men and women BUT
Science of developing a rectal microbicide is
challenging
– Long, open tunnel, fragile epithelium
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Money for rectal research not abundant in
current political climate
Research hampered by stigma, homophobia
Some argue to wait for proof of
concept of vaginal microbicide
MSMs Likely to Use a Rectal
Microbicide If Available
Reports indicate that 80% of MSMs use
lubricants 80% of the time. Condoms
only 59%.
• 41% of MSMs look for products
containing N-9, which we now
know is harmful.
• This is indicative that MSMs are likely to
use a microbicide if one were available

So, Where Are We?
Who is Doing the Work?
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biopharmaceutical companies
(~25)
non-profit research entities
(~38)
public-sector entities worldwide
(~5)
institutions conducting
supportive research (~36)
Alliance for Microbicide Development
Development will require
significant public money
Why
-
aren’t the big pharmaceuticals investing?
perceived low profitability
liability concerns
lack of in-house expertise
uncertain regulatory environment
For the last 20 years, almost all funding for
contraceptive development and related research
has come from governments and foundations.
What do these trials cost?
Laboratory
Testing
Phase 1
(safety)
Up to $13 Million
Phase 3
(efficacy)
Up to $50
Million
Phase 2
(safety)
Preliminary annual
funding needs
Actual 2004 funding levels
Additional annual funding needed
$3M
$3M
Policy and Advocacy
need $6M
Product Development & Trials
need $110M
$72M
Basic Scientific Research
need $130M
$65M
All combined:
Need $246M
All combined
need $246M
Annual funding
needs to double!
$38M
$65M
$140M
$0
$50
$106M
$100
$150
$200
$250
Millions of Dollars (2004)
$300
The Advocates’ Message
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There is a broad-based, demonstrable demand for
user-controlled prevention methods
North American and European Union investment
in microbicide research and development should be
- substantially increased and
- raised annually until first products available
Without this investment, we may not see usercontrolled HIV prevention tools available within this
decade.
Hastening the Day……
The Global Campaign for Microbicides
is working to
 Raise Awareness
 Accelerate Product Development
 Assure Access by Those Most in Need
 Hold Developers, Researchers
Accountable to High Ethical Standards
Goals of the Global Campaign
•
Mobilize resources and political will for increased
investment in microbicide research and worldwide
access to the female condom and other cervical
barrier methods;
•
Create a supportive policy environment for the
timely development, introduction and use of new
prevention technologies; and
•
Ensure that as science proceeds, the public interest
is protected and the rights and interests of trial
participants, users, and communities are fully
represented and respected
public
demand
public
awareness
political
support
increased
resources for
R&D ($$$)
all people know
about & have
access to affordable
microbicides
safe and
effective
microbicides on
the market
You Can Help in Many Ways
Visit www.global-campaign.org
There Are Many Ways You Can Help
1) Learn more about microbicides.
Visit the campaign website at
www.global-campaign.org
5) Host a microbicides film
night/discussion
2) Talk to everyone you know about
microbicides
6) Sign the Global Campaign
petition and help collect
signatures.
3) Sign up to get on the GC News
and Alliance email lists.
7) Get your organization to
endorse the Global Campaign.
4) Get any organizations,
community groups, or
networks you are involved
with to host a program on
microbicides.
8) Contact your policy makers
9) Write letters to the editor,
articles, etc., for local media
10)Add microbicides to your
group’s advocacy agenda
Impact of Microbicide
Positioning on
Acceptance and Use
Possible Positioning of
Microbicide Introduction
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For use in primary partnerships
For use by discordant couples
When couples seek to increase intimacy
When conception is desired (some products)
When partners refuse to use condoms
When it is too great a risk to ask partners to
use condoms
As a back-up for condoms already being
used
Put the Power to Protect
in YOUR Hands…
When You’re Ready to
Move a Little Closer…..
When he refuses
and you can’t…..
When you desire a baby,
but not HIV….
When you don’t want anything
to come between you…..
When You Want to Be
Extra Sure…..
Acknowledgements
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Anna Forbes
Lori Heise
Polly Harrison
Anna Foss
Peter Vickerman
Charlotte Watts
Alan Stone
Michael Gross
Anna-Barbara Moscicki
–
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–
–
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Peg Weeks
Maryann Abbott
Katherine Mosack
Robin Shattock
Global Campaign for
Microbicides
– Alliance for
Microbicide
Development