Www.global-campaign.org Rectal Microbicides: New Hope for HIV and STD Prevention

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Rectal Microbicides:

New Hope for HIV and STD Prevention


• Why we need rectal microbicides

• What is involved in development

• Where the research is

• What you can do to get involved

Objectives


Men at risk

• High rates of condom use are difficult to maintain, as the rate of new HIV infections shows

• New data reveals reasons for concern:–UK: 48.8% UAI in the past year–US: 30% UAI (HIV - men in past year)

• STD rates confirm UAI prevalence


Women at risk

• In large US survey, 35% of women age 25-44 report having had anal sex at some time in their life

• 32% of high-risk women reported anal sex in past 6 months (Gross et al, 2000)


What is a microbicide?

Microbicides are substances that can reduce the transmission of HIV and other STD pathogens when applied vaginally and, possibly, rectally.

They are not yet available.

Currently, they are formulated as lubes, gels or creams applied with an applicator like those shown here


We need a product that is…

• Inexpensive

• Easily accessible (over the counter)

• Easy to use

• Safe, non-irritating

• Available in various forms (in lubes, suppositories, on condoms)

• Effective


What if we had a complete HIV toolkit?

Prior to exposure

Point of transmission

Treatment

•Male and female condoms and lube

•ART to prevent perinatal transmission

•Clean injecting equipment

•Vaginal and rectal microbicides

•Cervical barriers

•Post-exposure prophylaxis (PEP)

•Improved antiretroviral therapy

•Treatment for opportunistic infections

•Basic care/nutrition

•Prevention for positives

•Education and behavior change

•Therapeutic vaccines

•Rights-focused behaviour change

•Voluntary counselling and testing

•STI screening and treatment

•Male circumcision

•Preventative Vaccines

•Pre-exposure prophylaxis (PREP)


Why vaginal microbicides?• Women currently have no way to protect

themselves when her partner won’t use a condom

• Women biologically more vulnerable to HIV

– 2-4 times more likely than men to get HIV from vaginal sex

• Women may be less able to assert their rights

• Current methods (abstinence, fidelity, and condom use) often require male consent, knowledge, or cooperation


Laboratory Testing

2-6 Years

Phase 3(efficacy)

2 to 4 Years

Simultaneous studies in some cases:HIV+, penile & rectal safety

10 or more years

3 products3 products

4 products30+ products

Phase 1(safety)

1 to 6 Months

Phase 2(safety)

Up to 2 Years

25 – 40 people

200-400 people

3,000-10,000 people

Vaginal Microbicide Research in 2005


How could microbicides work?

• Kill/inactivate/immobilize the virus• Boost body’s natural defenses• Prohibit viral entry by blocking fusion• Inhibit viral replication• Create a physical barrier

or some combination of these approaches


Physiological Differences

Vagina RectumMost 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


Research questions

• Infection – more to learn about anal intercourse and HIV infection

• Testing - What assays (tests) to measure impact?

• Distribution – how would it spread?

• Application Methods?

• Dosing – how much, what is acceptable?

• How does rectal shedding of HIV impact risk?


Laboratory research

To learn more about:

• How HIV infection occurs in the rectum – what cells are most vulnerable

• The impact of intercourse on rectal tissue (trauma, inflammation, speed of healing)

• What markers can we look at to determine impact of a product on the rectum?


Laboratory research in action

Dr. Ian McGowan, HPTN 056University of California/Los Angeles

Goal: To define measurements that can be made on rectal tissue biopsies that would be of use in rectal microbicide safety studies.

Repeated measurements on 16 men, and studied variation based on:– Time– Location in the rectum– Sero status


Penile Acceptability Studies

To learn more about…

• How much tissue is likely to be exposed to a microbicide

• Impact of a product on the penis


Distribution research in action:

Dr. Craig Hendrix at Johns Hopkins University in Baltimore

• Volunteers simulated anal intercourse

• MRI scans done up to five hours after its release

• Initial studies suggest that semen could travel up to 60 centimeters

• Showed where a microbicide would be needed to protect vulnerable tissues


Behavioral Research

To learn more about…• Prevalence of anal intercourse for both

mean and women – and how many of these acts are protected

• Preferences re: formulation and delivery systems

• Sexual practices that affect microbicide feasibility

• How much product is acceptable


Behavioral research in action:

Alex Carballo-Diéguez, Columbia Univ (NY)Ken Mayer, Fenway Community Health (Boston)

How much gel is tolerable?• 18 HIV uninfected men• Maximum acceptable dose for insertion

and anal intercourse


Behavioral research in action:

Alex Carballo-Diéguez and Sigma Research Center both did surveys of MSM interest in

using microbicide

Results:In San Francisco: 59% heard of

microbicides, 25% - 35% might use (depending on stated effectiveness)

In the UK: 23% had heard of microbicides, 59% might use


More vital steps

1. Men and women need education about the risks of unprotected anal sex

2. Safety trials on rectal application of vaginal microbicides that are currently in large scale trials

3. Testing over the counter lubes to see how safe they are

4. Advocacy for increased research


Rectal safety trials on vaginal products

• We won’t know if the first vaginal microbicides are effective for rectal use

• But we must know if they are safe to put in the rectum or not

• Because some people will try to use them rectally

• If deemed harmful for the rectum, labels warning against rectal use are imperative.


Testing on over the counter

lubesDrs. Sudol & Phillips at Population Council, New

York

• Tested 5 OTC lubes in mice to see if they caused damage to rectal cells

• KY-Plus (no longer on market) and DeLube caused the most damage

• Viamore, Vagisil and Astroglide caused some damage

• More research is underway, with findings expected soon.

• Need more research to see if these products cause damage to human rectal cells


Online Lube Survey

• 7,500 participants from 100 countries• 700 women• Data analysis by UCLA• Information on condom and lubricant

use, rectal microbicide acceptability• Help establish priorities for testing

lubes for rectal safety


• Microbicide research is drastically under-funded

• Need for increased funding for both vaginal and rectal microbicides– Talk to your government officials– e.g., U.S. Microbicide Development Act

Advocacy for rectal microbicides


Global Campaign for Microbicides

A worldwide effort co-sponsored by groups working on• HIV/AIDS• reproductive health• gay health• women’s empowerment

Working to educate, raise awareness and generate collective advocacy for increased political and public investment in microbicide development


New strategy to raise awareness and demand among gay men

Three components:• Internet – http://lifelube.org• Public presence in forums &

conferences• Media – print, electronic, guerilla!

LifeLube.org


International Rectal Microbicides Working GroupWorking Collaboratively:• Global listserv• Bi-monthly conference calls• Developed an advocacy agenda• To join, contact Jim Pickett, [email protected]

Presence at conferences: – Microbicides 2006 conference– Gay Men’s Health Conferences– Gay and Lesbian Medical

Association annual meeting


What you can do

Visit www.global-campaign.org or www.irmwg.org to

• Join the International Rectal Microbicide Working Group calls and listserve

• Learn more about rectal microbicides• Sign up for the Global Campaign’s

newsletter• Host a talk on microbicides – this and other

presentations available for download• Endorse the Global Campaign

Documents

Www.global-campaign.org Rectal Microbicides: New Hope for HIV and STD Prevention