science does not always produce the answer we hope for
The vaginal microbicide intervention that was part of the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial has been stopped because the microbicide gel has not proven to be effective in reducing acquisition of HIV. VOICE is being conducted in South Africa, Uganda, and Zimbabwe and was designed to test whether antiretrovirals, either as oral pills or as a vaginal gel, are safe and effective in preventing sexual transmission of HIV in women. On the cancellation of the microbicide arm of the trial, the New York Times reported:
In this case, 6 percent of women using the tenofovir gel and 6 percent of those using the placebo had become infected by the time the outside panel looked at the data. It was found to be safe but not effective, which ethically requires the cancellation of the trial to keep any more women from becoming infected.
VOICE was building on work from two previous streams of research: microbicide gels and pre-exposure prophylaxis (PrEP). In July 2010, the CAPRISA study estimated microbicide gels to have reduced HIV acquisition by an estimated 39 percent overall and 54 percent by women with high adherence. In November 2010, the iPrEx study showed that MSM study participants who took a daily dose of oral antiretrovirals experienced an average of 44 percent fewer HIV infections than those taking a placebo. Findings from both studies were widely celebrated, seen as potential answers to stemming the tide of the AIDS epidemic.
The VOICE trial was particularly interesting because of its focus on preventing HIV in women. In Africa, it is estimated that 60 percent of the HIV-infected are women. Many believe the interventions VOICE was testing would be more effective than previous interventions (e.g. condoms) because women would be less likely to have to inform partners of their use. The VOICE trial innovated on earlier work by pitting the different prevention methods against each other, having the potential to identify which was most effective. VOICE had three treatment conditions: the vaginal microbicide tenofovir gel, and two oral pre-exposure prophylaxis drugs: oral tenofovir pre-exposure prophylaxis and oral pre-exposure prophylaxis using the tenofovir/emtricitabine combination pill Truvada.
The discontinuation of the tenofovir microbicide intervention arm of the trial was not the first set of disappointing news to come out of the VOICE trial. Earlier this year, the oral tenofovir arm was stopped…
…after the independent Data and Safety Monitoring Board for the VOICE study concluded that even if the trial ran to its planned conclusion, it would be impossible to demonstrate any significant difference in effect between oral tenofovir and a dummy pill (a placebo) in preventing new HIV infections.
Needless to say, the problems faced by the VOICE trial are particularly disappointing for those who were hoping to champion alternatives for women to keep themselves from getting infected with HIV.
One of the investigators in the VOICE trial, Professor Salim Abdool Karim–who was also the principal investigator on the CAPRISA study–had this to say about the failed microbicide intervention:
“These results were totally unexpected as there is good evidence from laboratory research, animal studies and human trials showing that tenofovir gel prevents HIV. However, science does not always produce the answer we hope for. This is particularly pertinent when a drug’s effectiveness is dependent on a complex combination of the biological activity of the drug and the human behaviour influencing use of the drug as prescribed during the study. I look forward to seeing the complete results and, in particular, an analysis of whether the drug levels in the female genital tract provides any clues to the study’s outcome.”
Karim’s statement makes clear that even if a biomedical intervention was found to be efficacious, ultimately all interventions rely on the behavior of individuals to be effective. Because he is an investigator, I presume he has a number of behavior-related hypotheses as to why the intervention failed. I’ll be on the lookout for any analysis to be published from the study and will share with haba na haba readers anything that comes out.