World's third rectal microbicide trial launched in Pittsburgh

International Rectal Microbicide AdvocatesOct 14 2010

Calls for more funding to strengthen field

The world's third rectal microbicide trial launched in Pittsburgh, Pennsylvania today, with sites preparing to open in Boston, Massachusetts, and Birmingham, Alabama soon. Scientists will test the rectal safety and acceptability of tenofovir gel, a microbicide developed for vaginal use that has shown promise for preventing HIV through vaginal intercourse. Depending on the outcome of this new study, tenofovir gel could be further evaluated to determine if it can reduce the risk of HIV among both men and women who engage in receptive anal intercourse.

"International Rectal Microbicide Advocates (IRMA) congratulates the Microbicide Trials Network and its partners on the launch of this very important study - the third Phase I trial in history to look at the safety and acceptability of a microbicide gel applied rectally," said Jim Pickett, IRMA Chair and Director of Advocacy at AIDS Foundation of Chicago. "This brings us another step closer to the development of safe and effective rectal microbicides for use during anal intercourse," he said.

Condoms are considered the gold standard for the prevention of HIV and STDs during sexual intercourse, but not all receptive partners are able or willing to use condoms every time. An act of anal intercourse that is not protected by a condom is 10 to 20 times more likely to result in HIV transmission compared to an act of unprotected vaginal intercourse, due to the fragility of the rectal lining and the large presence of cells targeted by HIV. New methods to protect against the sexual transmission of HIV are urgently needed. Strategies beyond condoms - such as vaccines, oral prevention, and microbicides - will provide individuals with more prevention options.

Microbicides - substances applied topically on the inside of the rectum or vagina - could potentially help prevent the transmission of HIV. The research and development of vaginal microbicide candidates is much more advanced than research on rectal microbicides. Tenofovir gel, for example, is a candidate microbicide specifically developed to prevent vaginal transmission of HIV. In a recent study known as CAPRISA 004, tenofovir gel was found to significantly reduce the risk of HIV among at-risk women who were instructed to use the gel before and after vaginal intercourse. In an ongoing, large-scale effectiveness trial called VOICE - Vaginal and Oral Interventions to Control the Epidemic - researchers from the U.S. National Institutes of Health-funded Microbicide Trials Network (MTN) are testing daily use of tenofovir gel in African women, with results expected in 2013.

This new Phase I rectal microbicide study, known as MTN-007, aims to determine if rectal use of tenofovir gel is safe, and in particular, does not cause cells in the rectum to become more vulnerable to HIV. Investigators will also ask trial participants questions regarding the gel's desirability. MTN-007 will enroll 60 men and women at the University of Pittsburgh, the University of Alabama at Birmingham, and Fenway Health in Boston. Leading the study is Ian McGowan, M.D., Ph.D., of the University of Pittsburgh, who is also co-principal investigator of the MTN and serves as Scientific Vice-Chair of IRMA.

Little is known about tenofovir gel used rectally, but science is advancing our understanding. Laboratory and animal studies involving rectal application of tenofovir gel have suggested it's safe for testing in humans. In fact, MTN researchers have just completed the first Phase I trial with eighteen participants, called RMP-02/MTN-006, in collaboration with the Microbicide Development Program at the University of California, Los Angeles. While results of RMP-02/MTN-006 are not expected until early 2011, researchers have already recommended modifications to the gel's formulation. MTN-007 is evaluating the new formulation, which still contains the same amount of active drug - 1% percent tenofovir - but has a lower concentration of glycerin (an additive found in many types of products) to make it more amenable for rectal use.

"It is very encouraging to see the rectal microbicide field moving forward," said IRMA Community Vice-Chair Kadiri Audu, who also heads up the IRMA Nigeria chapter, "and I look forward to trials taking place in Africa as well." He continued, "Gay men and other men who have sex with men in Africa have high rates of HIV infection, and we know unprotected heterosexual anal sex is relatively common on the continent and contributes a sizable number of HIV infections. As much as we need vaginal microbicides to give women an extra prevention tool, rectal microbicides for the women, men, and transgender individuals who engage in anal intercourse are absolutely essential as well."

While the rectal microbicide field has gained significant momentum, more focus and resources are necessary. In 2010, U.S. $7.2 million is being spent globally on rectal microbicide research. IRMA has calculated that annual investments must increase by 40% from 2011 - 2014, to U.S. $10 million/year and must increase further to U.S. $44 million (a six-fold increase) in the years 2015 - 2020 to ensure a minimum of candidate products are moving through the research pipeline into advanced testing for effectiveness.