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Vaginal and Rectal Microbicides:
An Update
M2010 Pre-Conference Workshop, 22 May 2010
Marc-André LeBlanc
What is a microbicide?
A product applied in the vagina or the rectum
that can offer protection against HIV and,
ideally, other STI pathogens
Microbicides are still in development
they are not available yet!
Gel,
lubricant
Vaginal
ring
Suppository
Rectal
Applicator
Film
Enema
Examples of how a microbicide might be delivered
How would a microbicide work?
ARV-based
non-ARV-based
•Blocks specific proteins of HIV so
that it cannot bind with a healthy
cell
• Prevents HIV from entering
healthy cells by creating a barrier
between the cell and HIV
• Blocks receptors on healthy cells
so that HIV cannot bind with them
• In the case of a vaginal
microbicide, could enhance the
vagina’s natural defense system
• Deactivates key components of
the HIV to inhibit replication
• Kills the virus by attacking it
Comparing ARV-based
and non-ARV-based microbicides
ARV-based
More potent against HIV
Advantages
Non-ARV-based
Could work against HIV and
other STIs
May be long lasting
Could be contraceptive
Not contraceptive
May be more toxic
Disadvantages
May cause resistance
Unlikely to protect
against other STIs
May be less potent against
HIV
May need to be used at time
of sex
Source: Global Campaign for Microbicides
Why would HIV+ people want
microbicides?
To reduce the risk of co-infection with
other HIV strains.
 To reduce the risk of other sexually
transmitted infections, and yeast and
bladder infections.
 To allow conception whilst protecting
partner.

If ARV-based microbicides work…
1. Only taken if you KNOW you are HIV negative.
–So regular HIV testing is necessary.
2. May be available by prescription only.
–So access to a qualified health care provider is
necessary.
3. Only the dosing used in trials is known to work.
–For now, must be applied daily or before sex.
Science
Biological challenges
Vagina
Rectum
Most of the epithelium is 40
cell layers thick
Very fragile epithelium,
1 cell layer thick
Fewer CD4 cells than rectum
More inflammatory cells under
surface
(CD4 receptors)
Acidic pH
Alkaline, rather than acidic pH
Enclosed pouch
Open-ended tube
Anatomy 101
The Product Pipeline
1 product in
large-scale
efficacy trials
8 products in
human safety
trials
Pre-clinical testing:
More than 50
candidates
early-stage
concepts
Source: Alliance for Microbicide Development, with thanks to Anna Forbes
Research activities
• Pre-clinical/basic science
– developing and testing products in labs and in
animal studies
• Clinical trials – safety and efficacy
– Are these products safe? Do they work?
• Acceptability & behavioural studies
– What kinds of products would people use?
– Who is having sex? What kind?
Outcomes of past studies
Signs of efficacy
Safe
Trend
toward
harm
No efficacy
Carraguard®
BufferGel®
PRO 2000 0.5%
Nonoxynol-9
Savvy
Cellulose sulphate
Most advanced & large-scale trials
Product
Trial sponsor
Phase
Location(s)
Results
expected
Tenofovir gel
CAPRISA/CONRAD/
USAID/FHI
Tenofovir gel
MTN
2b
South Africa
July 2010
2b
South Africa, Uganda,
Zambia, Zimbabwe
2012
More products & trials
ARV-based
Non-ARV-based
Running
p2- Tenofovir gel (V)
p1- Tenofovir gel (V)
p1- BufferGel Duet (V)
p1- Ethanol gel (men, G-STI)
p1- VivaGel (V)
Planned
p3- Tenofovir gel (V)
p2- Dapivirine ring (V)
p2- Dapivirine gel (V)
p1- Tenofovir gel (R)
p1- UC-781 gel (R)
p1?- PC-815 gel (V)
p3- BufferGel (V-STI)
p1?- CAP tablet (V)
When can we expect a
microbicide?
• Next late stage trial results due in 2010.
• If successful:
– a larger trial may be needed to confirm the results
– then it can take one to two years for product review and
licensing in each country.
• If unsuccessful:
– wait for results from candidates now in earlier trials.
What can you do?
For more information…
• Global Campaign for Microbicides
– www.global-campaign.org
• International Rectal Microbicide Advocates
– www.rectalmicrobicides.org
• African Microbicides Advocacy Group
– www.global-campaign.org/amag
• International Partnership for Microbicides
– www.ipm-microbicides.org
Questions?