Rectal formulation of tenofovir gel safe and acceptable in early phase clinical study

A gel formulation of the antiretroviral drug tenofovir designed specifically for rectal use was found safe and acceptable, according to a Phase I clinical study led by the U.S. National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), and presented today at the 19th Conference on Retroviruses and Opportunistic Infections (CROI). The results of the study, which included HIV-negative men and women who used the gel rectally once a day for one week, serve as an important step toward the development and testing of a rectal microbicide to prevent HIV from anal sex.

Microbicides, products applied on the inside of the rectum or , are being studied as an approach for preventing or reducing the sexual . The majority of microbicide research has focused on products to prevent through , yet the risk of becoming infected with HIV from unprotected anal sex may be 20 times greater than unprotected vaginal sex. Developed as a vaginal microbicide, gel was reformulated with less , a common additive found in many gel-like products, in the hopes of making it more appropriate for rectal use.

The study, known as MTN-007, began in October 2010 and enrolled 65 men and women at three sites – the University of Pittsburgh, University of Alabama at Birmingham and Fenway Health in Boston. It is a follow-up trial to an earlier study, RMP-02/MTN-006, which assessed the rectal use of the vaginal formulation of tenofovir gel. That study found the gel produced a significant antiviral effect when used in the rectum, but gastrointestinal were problematic.

In MTN-007, study participants were randomly assigned to one of four study groups. Three of these groups were assigned to use one of the following products for a one-week period: a rectal formulation of tenofovir gel; a placebo gel containing no active ingredient; or a gel containing the spermicide nonoxynol-9. A fourth group did not use any gel but took part in all of the study-related procedures and tests, including physical and rectal exams.

Study results indicated no significant differences in side effects among the three gel groups. Eighty percent of participants reported only minor side effects related to the use of study products, while 18 percent reported moderate side effects. (Two study participants reported severe adverse events, but they were not deemed to be related to use of the study products.) Participants' adherence to the use of their assigned study products was high, with 94 percent using the products daily as directed. When asked about the likelihood that they would use the gel in the future, 87 percent of the participants who used the rectal formulation of tenofovir gel indicated they would likely use the gel again, compared to 93 percent of the placebo gel group, and 63 percent of the nonoxynol-9 gel group. In addition to assessing safety and acceptability, researchers also conducted preliminary gene expression testing, and noted changes in the activation of some genes in the tenofovir gel group, which they are continuing to evaluate to understand more fully.

"These findings tell us that the 'rectal-friendly' version of tenofovir gel was much better tolerated than the vaginal formulation of the gel when used in the rectum," said Ian McGowan, M.D., Ph.D., co-principal investigator of the MTN and professor of medicine, Division of Gastroenterology, Hepatology and Nutrition and Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine. "We are very encouraged that the rectal gel was quite safe, and that most people who used it said they would be willing to use it in the future."

As follow-up to MTN-007, researchers are now planning a Phase II, multi-site trial called MTN-017 that will involve186 men who have sex with men and transgender women at clinical sites in Peru, South Africa, Thailand, and the U.S. Participants will cycle through three study regimens: rectal tenofovir gel used daily, rectal tenofovir used before and after anal sex, and daily use of the antiretroviral tablet Truvada®. MTN-017 will allow researchers to collect additional information about the gel's safety and acceptability in the , and compare it to the use of Truvada.

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