A major HIV prevention trial comparing a tenofovir
microbicide with two forms of oral pre-exposure prophylaxis as HIV prevention
methods for women is to halt investigation of oral tenofovir pre-exposure prophylaxis, the
Microbicide Trials Network announced on Wednesday.
The decision was taken 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.
The VOICE trial (Vaginal and Oral Interventions to Control
the Epidemic) was designed to compare tenofovir microbicide gel, oral tenofovir
pre-exposure prophylaxis and oral pre-exposure prophylaxis using the tenofovir
/ emtricitabine combination pill Truvada.
The study also contains two placebo arms: a placebo gel arm and a placebo
VOICE has recruited 5,029 women at 15 trial sites in Uganda, South
Africa and Zimbabwe. About 1,000 women will
stop taking tenofovir in the study. The trial will continue to test tenofovir
microbicide gel and Truvada, and
women who are receiving oral tenofovir will be informed of the need to stop
taking the drug at their next scheduled study visit.
Final results from the study are expected in early 2013,
after all participants have completed at least one year of follow-up.
“Of course we are disappointed to hear that the tenofovir
pill arm of VOICE will not be able to answer the question of whether or not the
drug prevents HIV infection in women in this study,” said Mitchell Warren, AVAC
“This development raises as many questions as answers about
how oral pre-exposure prophylaxis, or PrEP, might work for women, making the
continuation of the VOICE study, along with other research for new HIV
prevention options for women, as essential as ever,” Warren added.
Halima, Director of the Global Campaign for Microbicides, stressed the value of
“With the good news that PrEP has been shown in studies to reduce HIV
risk in men who have sex with men, serodiscordant couples, and sexually active
heterosexual men and women, the key question remains—do we have sufficient
evidence that PrEP works in women? For this reason, VOICE continues to be an
exceptionally important study.
"Not only does it include both oral PrEP and a
vaginal microbicide in the same trial, but VOICE, we hope, will help provide
the evidence we need to bring us closer to delivering two more options for
Tenofovir-only PrEP was shown to be effective by the
Partners study, which announced results in July 2011. That study compared
pre-exposure prophylaxis with either tenofovir or Truvada with a placebo arm,
and found that the risk of infection was reduced by 62% in the tenofovir arm
and by 73% in the Truvada arm. The
difference between the two active drugs was not significant. That study
recruited both men and women.
Another study, conducted only in women, has shown a lack of
effect of PrEP using Truvada. The FEM PREP
study was halted in April 2011 after the study’s Data and Safety Monitoring
Board concluded that the trial would be unable to show a preventive effect of
Truvada PrEP even if it ran to its planned conclusion.
On the other hand the
TDF-2 study, which recruited both men and women in Botswana, has
shown that Truvada reduced the risk
of infection by 63%. The study was not designed to evaluate whether Truvada was equally effective at
preventing infection for men and for women. Results from the TDF-2 study were
announced in July 2011.