A disappointing setback in microbicide research was announced on Black Friday, as a gel intended to protect women from HIV was dropped from an important study because it didn't prove to be effective.
The vaginal microbicide gel was the second "arm," or experiment, to be dropped from the the VOICES (Vaginal and Oral Interventions to Control the Epidemic) trial in Africa. Both the gel and the pill dropped from the study in September contained a drug called tenofovir. A Truvada pill is still being tested in the study.
While the news was an unpleasant surprise, it's critical to continue moving forward with microbicide research, said Jim Pickett, chair of the International Rectal Microbicide Advocates. Pickett is also director of prevention advocacy and gay men's health for the AIDS Foundation of Chicago.
"This is tough news to hear, so soon after the tenofovir tablet arm stopped, and we are certainly disappointed," Pickett said in a statement. "The field has placed a great deal of hope - and resources - in the development of vaginal tenofovir gel and no one is happy about such an outcome."
The scientific path is a long, challenging and often confounding one, the statement said. While this wasn't information anyone wanted to hear, we will learn much about why tenofovir gel did not work in this well-conducted trial. At the moment we do not know whether this was a matter of adherence, biology, or sexual behaviors - or a combination of all three.
This is the full IRMA statement:
IRMA Expresses Disappointment; Calls for MTN 017 to Move Forward (Nov. 25, 2011)
International Rectal Microbicide Advocates (IRMA) expresses disappointment regarding today's announcement that the vaginal tenofovir gel arm in the Microbicide Trial Network's VOICE trial is being discontinued. VOICE has been exploring two ARV-based HIV prevention approaches since it began enrolling women in high incidence areas in South Africa, Uganda and Zimbabwe in 2009.
The MTN announced that the VOICE arm studying daily vaginal application of tenofovir gel was stopping after a regular review of study data conducted by the independent Data Safety Monitoring Board revealed that the gel, while safe, was not effective at preventing HIV infection in women. Less than two months ago, VOICE announced the discontinuation of its study arm testing tenofovir tablets because they also were shown to not be effective at preventing HIV in the trial. VOICE will continue to study the safety and efficacy of Truvada tablets.
"This is tough news to hear, so soon after the tenofovir tablet arm stopped, and we are certainly disappointed," said Jim Pickett, IRMA chair. "The field has placed a great deal of hope - and resources - in the development of vaginal tenofovir gel and no one is happy about such an outcome."
The scientific path is a long, challenging and often confounding one. While this wasn't information anyone wanted to hear, we will learn much about why tenofovir gel did not work in this well-conducted trial. At the moment we do not know whether this was a matter of adherence, biology, or sexual behaviors - or a combination of all three.
"Too often heterosexual transmission is presumed, by default, to be through unprotected vaginal intercourse. It will be interesting to learn how much anal intercourse was being reported in the trial. Unprotected anal intercourse is 10 to 20 times more likely to result in HIV transmission compared to unprotected vaginal intercourse. If even a small portion of VOIC E participants were practicing unprotected anal intercourse, this may have confounded the efficacy of the vaginal gel being tested," said Pickett.
It is critical that the planned MTN 017 Phase II rectal microbicide trial moves forward. MTN 017 will study a modified formulation of tenofovir gel, to be applied rectally among gay men and other men who have sex with men (MSM) in Thailand, South Africa, Peru and the United States with a proposed launch in mid-2012. While moving forward with MTN 017 is dependent on the MTN 007 study which tested rectal safety and acceptability of this gel, we expect results soon. If the results indicate this modified formulation of tenofovir gel is both safe and acceptable when used rectally, MTN 017 must happen.
"Gay men and other MSM suffer very high prevalence rates in every part of the world, and their primary exposure is from unprotected anal intercourse. It is therefore an imperative we study products for rectal use. The rectum is a more fragile environment than the vagina and has other characteristics that increase the chances for HIV infection to take hold," said Pickett. "As anal intercourse is a human behavior not confined to gay men and other MSM - we all have rectums after all- developing safe, effective, acceptable and accessible rectal microbicides will be important to the health and well-being of millions of women and men in Africa and throughout the world."
IRMA is pleased the FACTS 001 study, a Phase III trial in South Africa testing the same regimen of tenofovir gel used in CAPRISA 004, plans to continue . IRMA is also excited about the upcoming Phase III trial testing a vaginal ring containing the ARV dapivirine. Delivery methods such as vaginal rings may improve adherence and drug availability.