Charlene Dezzutti, Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and lead researcher of the MTN Network Laboratory, explained:
"The lining of the rectum is much more fragile than the vaginal epithelium, so we can't be certain a product like tenofovir gel that is safe for vaginal use will be completely safe to use in the rectum.
We are very encouraged by our laboratory data that suggests the reformulated gel could be safer for rectal use, and serve as a dual compartment gel for use in both the vagina and rectum."
Individuals who have unprotected anal sex are 10 to 20 times more likely to contract HIV than those who have unprotected vaginal intercourse. Even though the gel has shown promise in reducing HIV risk in women through vaginal sex, the gel may not be safe to use rectally, as rectal lining (rectal epithelium) is considerably thinner than vaginal lining.
Tenofovir gel is hyperosmolar, meaning it contains a higher concentration of sugars and salts relative to cells. As a result, epithelial cells achieve balance by loosing water, which results in shrinkage, which in turn could make the rectal epithelium less efficient in protecting against HIV.
Therefore, researchers from CONRAD reformulated the gel by reducing the amount of glycerin in order to make it more amenable to rectal use. MTN researchers then tested the reformulated gel and found that it was three times less likely to cause cells in rectal tissue to release water and that it was just as effective at protecting against HIV as the vaginal formulation.
Results from an early phase clinical trial that involved 65 HIV-negative men and women who used the gel rectally once a day for one week, indicated that it was safe and acceptable in the participants. Results from this study, as well as future ones will be vital for the development of a rectal microbicide that could help protect against HIV or other sexually transmitted infections during anal sex.
The team are currently planning a Phase II, multi-site trial at clinical sites in the U.S., Peru, Thailand and South Africa. The trial will involve 186 men who have sex with men, and transgender women. Participants in the United States will undergo three regimens:
- reduced glycerin tenofovir gel used daily
- reduced glycerin tenofovir gel used before and after anal sex
- daily use of the antiretroviral tablet Truvada
Written by Grace Rattue