Closure of oral Tenofovir arm in VOICE Pre-Exposure Prophylaxis trial: PrEP as a “niche intervention”?
The Microbicides Trial Network (MTN) announced yesterday that its VOICE (Vaginal and Oral Interventions to Control the Epidemic, MTN003) HIV Pre-Exposure Prophylaxis (PrEP) prevention study will discontinue the daily oral tenofovir arm of the trial. The decision follows an interim review of the trial’s data by its Data Safety and Monitoring Board (DSMB) which recommended that VOICE stops evaluating the oral tenofovir tablet (TDF, brand name Viread), because it will not be possible for the study to show a difference in effect between the drug and the placebo tablet (futility) for the prevention of HIV infection in the context of that study. Importantly, the DSMB did not found any safety issues associated with the use of TDF in any arm of the trial.
This is the third PrEP trial, after FEM-PrEP and TDF2, for which an interim review of the trial’s data led to a change of course of the study. Because the four other arms of the VOICE trial continue, there are no data available publicly yet to explain why tenofovir would not show effectiveness in this study when three other studies showed a dramatic reduction in the risk of HIV infection with tenofovir alone or in combination with another antiretroviral (see table below). However, Sharon Hillier and Ian McGowan of the Microbicide Trials Network noted that the study’s population – predominately women in their 20’s, could be an important factor.
“If there’s one thing we’ve learned over the years it’s that unmarried women in their 20s are in a very different place in their lives than married women in their 30s. People in different circumstances will make different choices about their use of condoms, their choice of partners and whether or not to use a biomedical prevention product. As we continue the VOICE trial we recognize that there could be many factors that influenced the outcome with oral tenofovir, and even when we have more information available to us, understanding what exactly happened (or not) will not be simple.”
If confirmed (a full analysis of the data will not be available before several months) this would add to the challenge of defining a strategic use for PrEP in the general population or in populations at risk.
In sub-Saharan Africa where unprotected heterosexual intercourse is the primary driver of the epidemic, women account for 60 percent of adults with HIV. Young women are especially vulnerable being up to five times more likely to become infected with HIV than young men, and more than a quarter of all new global HIV infections occur in women aged 15-24.
|Slide presented by Slim Abdool Karim during the IRMA teleconference “Yes, Africa Needs Rectal Microbicides” 27 September 2011|
If PrEP is not an appropriate choice for these most vulnerable young women, then the relevance of the approach in this context and population is calling for questions (FEM-Prep also enrolled women of mean age 24 years). It will be critical to understand what has happened in VOICE and FEM-PrEP to ensure that PrEP remains a viable and efficient option for HIV prevention. Acceptability, use, adherence, biodistribution will undoubtedly be important contributory and explanatory factors. Data from previous and other ongoing trials in different populations, different contexts and using different drugs will provide crucial information to help identify who would benefit best from PrEP.
Data currently available do not exclude a potential PrEP roll-out but gradually hint at a targeted use of PrEP in vulnerable populations. PrEP is not for everybody and the outcome of these studies may not be that PrEP could become a “boutique intervention” but rather a “niche intervention” with great efficacy at individual level, poor efficiency as a systemic intervention, and limited effectiveness for curbing the epidemic at population level, but would nevertheless contribute to preventing a number of HIV infections. PrEP and in particular intermittent PrEP still has an important role to play (once shown to work) with other options and structural interventions that need to be developed and implemented simultaneously to ensure that a broad range of needs are addressed with appropriate and acceptable solutions.
Altogether, we can create a prevention environment that will lead to the taming of this epidemic toward zero new infection.
|Source: AVAC. More information about ongoing PrEP research is available at avac.org/prep.|