Rectal Microbicides: New Hope for Non-Condom Prevention of HIV and other STDs

Why we need rectal microbicides What is involved in development Where the research is at Why this is a political issue 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 STD rates confirm UAI prevalence

Women at risk In large US survey 35% women age 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) In a Chinese study of 1300 people from 41 cities, nearly 70% of men and women reported engaging in anal intercourse (Burton 1990)

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 -- how effective?

What if we had a prevention spectrum? 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 Improved ART (including pediatrics) Post-exposure prophylaxis (PEP) Treatment for opportunistic infections Basic care/nutrition Rights-focused behaviour change VCT STI screening and treatment Vaccines Pre-exposure prophylaxis (PREP)

Why vaginal microbicides? Women currently have no way to protect themselves when man won’t use a condom Women biologically more vulnerable to HIV –2-4 times more likely than men to get HIV from unprotected 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: HIV+, penile & rectal 10 or more years 5 products 3 products 6 products products Phase 1 (safety) 1 to 6 Months Phase 2 (safety) Up to 2 Years 25 – 40 people people 3,000-10,000 people Vaginal Microbicide Research in 2005

How could microbicides work? Kill/inactivate/immobilize the virus Prohibit viral entry by blocking fusion Inhibit viral replication Create a physical barrier or some combination of these approaches

Physiological Differences VaginaAnus-colon-rectum Most of the epithelium is 40 cell layers thick Very fragile epithelium, 1 cell layer thick. Other and fewer CD4 cells than rectum More inflammatory cells under surface (CD4 receptors) Acidic pHAlkaline, rather than acidic pH Enclosed pouchOpen-ended tube 2 feet in length up to spleen

Anatomy 101: The Rectum and Colon

Research questions Dosing – how much, what is acceptable? Application Methods? Dilution – how would it spread? What assays (tests) to measure impact? How does rectal shedding of HIV impacts risk? Using baseline research, clinical studies and behavioral research to investigate.

Laboratory research To learn more about: The impact of intercourse on rectal tissue (trauma, inflammation, speed of healing) How HIV infection occurs in the rectum – what cells are most vulnerable What markers can we look at to determine impact of a product on the rectum?

Laboratory research in action: Dr. Ian McGowan, University of California/Los Angeles Measure the physical changes in their rectal tissue caused by anal intercourse Set a baseline to measure changes observed in later rectal safety trials

Distribution Research & Penile Irritation Studies To learn more about… How semen is distributed after intercourse 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 “Semen" could travel up to 60 centimeters (approx 2 feet) Showed where a microbicide would be needed to protect vulnerable tissues

Behavioral Research To learn more about… Prevalence of unprotected anal intercourse – both men and women Preferences re: formulation and delivery systems Sexual practices that affect microbicide feasibility How much product is acceptable

Behavioral research in action: Alex Carballo-Diéguez and Ken Mayer Columbia University (NY) and Fenway Community Health (Boston) Volume escalation trial 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

Research Overview WhatWho/Where/WhenType HPTN-056 Mucosal safety parameters UCLA Lab Microbicide Development Program U projects - UCLA, Johns Hopkins, NIH, 3 biotech firms to 2009 Lab, Clinical, Behavioral Additional acceptability studies Alex Carballo-Dieguez & Ken Mayer Behavioral

More vital steps 1.Safety trials on what happens if rectal application of first vaginal microbicides 2.Testing over the counter lubes to see how safe they are 3.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 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 Need more research to see if these products cause damage to human rectal cells

Microbicide research is drastically under-funded Pressure not to address anal sex Need legislation that would increase research support for both vaginal and rectal microbicides –e.g., Microbicide Development Act in U.S. 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 – Public presence in forums & conferences Media – print, electronic, guerilla! LifeLube.org

Rectal Microbicides Working Groups Organizing internationally in the US, UK, Canada Presence at –Microbicides 2004 and 2006 conferences –UK CHAPS conference –Gay Men’s Health Summits in Canada and US –Gay and Lesbian Medical Association annual meeting in Montreal –Gay Men’s Health Summits in Canada and US Working Collaboratively Meeting by bi-monthly conference call To join, contact Jim Pickett,

What you can do Visit or to 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 Write to your legislators Join the Rectal Microbicide Working Group calls