Rectal Microbicides:
New Hope for HIV and STD Prevention
www.global-campaign.org
Objectives
• • • • Why we need rectal microbicides What is involved in development Where the research is What you can do to get involved
www.global-campaign.org
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
www.global-campaign.org
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)
www.global-campaign.org
What is a microbicide?
transmission of HIV and other STD pathogens when applied vaginally and, possibly, rectally.
Microbicides are substances that can reduce the
They are not yet available.
Currently, they are formulated
as lubes, gels or creams applied with an applicator like those shown here
www.global-campaign.org
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
www.global-campaign.org
• • • • •
What if we had a complete HIV toolkit?
Prior to exposure • Rights-focused behaviour change • Voluntary counselling and testing • STI screening and treatment • Preventative Vaccines Point of transmission • Male and female condoms and lube • ART to prevent perinatal transmission • Clean injecting equipment • Vaginal and rectal microbicides Treatment • Improved antiretroviral therapy • Treatment for opportunistic infections • Basic care/nutrition • Prevention for positives • Education and behavior change • Therapeutic vaccines
www.global-campaign.org
• Pre-exposure prophylaxis (PREP)
• Male circumcision
• Cervical barriers
• Post-exposure prophylaxis (PEP)
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
www.global-campaign.org
Vaginal Microbicide Research in 2005
3 products 10-20 products 6 products
5 products
Laboratory Testing 2-6 Years
Phase 1 (safety) 1 to 6 Months
25 – 40 people
Phase 2 (safety) Up to 2 Years
200-400 people
Phase 3 (efficacy) 2 to 4 Years
3,000-10,000 people
Simultaneous studies in some cases: HIV+, penile & rectal safety
10 or more years
www.global-campaign.org
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
www.global-campaign.org
Physiological Differences
Vagina
Most of the epithelium is 40 cell layers thick Fewer CD4 cells than rectum Acidic pH Enclosed pouch
Rectum
Very fragile epithelium, 1 cell layer thick. More inflammatory cells under surface (CD4 receptors) Alkaline, rather than acidic pH Open-ended tube
www.global-campaign.org
Anatomy 101
www.global-campaign.org
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?
www.global-campaign.org
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?
www.global-campaign.org
Laboratory research in action
Dr. Ian McGowan, HPTN 056 University 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
www.global-campaign.org
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
www.global-campaign.org
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
www.global-campaign.org
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
www.global-campaign.org
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
www.global-campaign.org
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
www.global-campaign.org
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
www.global-campaign.org
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.
www.global-campaign.org
Testing on over the counter lubes
Drs. 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
www.global-campaign.org
Advocacy for rectal microbicides
• Microbicide research is drastically underfunded • Need for increased funding for both vaginal and rectal microbicides
– Talk to your government officials – e.g., U.S. Microbicide Development Act
www.global-campaign.org
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
www.global-campaign.org
LifeLube.org
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!
www.global-campaign.org
International Rectal Microbicides Working Group
Working Collaboratively: • Global listserv • Bi-monthly conference calls • Developed an advocacy agenda • To join, contact Jim Pickett, jpickett@aidschicago.org Presence at conferences: – Microbicides 2006 conference – Gay Men’s Health Conferences – Gay and Lesbian Medical Association annual meeting
www.global-campaign.org
What you can do
Visit www.global-campaign.org or www.lifelube.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
www.global-campaign.org