Tenofovir PrEP arm dropped in women's HIV prevention trial

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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 tablet arm.

Glossary

oral

Refers to the mouth, for example a medicine taken by mouth.

microbicide

A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

serodiscordant

A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

HIV-associated neurocognitive disorder (HAND)

HIV-associated neurocognitive disorder (HAND) describes the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the central nervous system (CNS) during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. Cognitive impairment in people with HIV is not necessarily due to HAND; other possible causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment and Alzheimer’s disease.

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 Executive Director.

“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.

Yasmin Halima, Director of the Global Campaign for Microbicides, stressed the value of VOICE.

“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 women.”

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.