Another arm of the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial has been discontinued, the National Institute of Allergy and Infectious Diseases at the National Institutes of Health announced Friday.
The Data Safety Monitoring Board (DSMB) recommended the discontinuation of the daily one percent tenofovir vaginal gel arm of the study during a routine trial review when there was no difference in effect demonstrated between the drug-containing gel and the placebo gel groups, according to an NIH press release.
The VOICE study – the first to compare the safety and efficacy of oral versus topical pre-exposure prophylaxis (PrEP) interventions in the prevention of sexually transmitted HIV – tested three PrEP strategies among 5,000 women at various study sites in Africa. The daily oral tenofovir arm of the trial was discontinued in late September when a DSMB determined the trial would not be able to show that tenofovir tablets effectively protected women from HIV infection. The third study arm looking at daily administration of oral Truvada (a combination therapy containing tenofovir and emtricitabine) will continue.
“These results were totally unexpected as there is good evidence from laboratory research, animal studies and human trials showing that tenofovir gel prevents HIV,” said Salim Abdool Karim, MD, PhD, director of the Center for the AIDS Program of Research in Africa (CAPRISA). “However, science does not always produce the answer we hope for.”
The CAPRISA 004 trial, whose results were announced in July 2010 at the International AIDS Conference in Vienna, showed that one percent tenofovir vaginal gel used by women before and after sex reduced HIV infection by 39 percent and genital herpes by 51 percent. During a call with bloggers Monday, Stefano Bertozzi, MD, director of HIV and Tuberculosis (TB) at the Bill & Melinda Gates Foundation, said the problem likely lies in adherence.
“We’re not sure why daily use of the microbicide didn’t work, but suspect it has to do with women’s adherence to study protocol and the suspicion that it was not used every day,” Bertozzi said. “Adherence has been the biggest problem with daily use products.”
Systemic and topical medicines not dependent on daily adherence are needed, he said, mentioning the currently ongoing study of the dapivirine vaginal ring and a potential injectible – much like the contraceptive that women receive every three months – for men who have sex with men.
South Africa is moving forward with a confirmatory trial of CAPRISA with a similar dosing schedule, Bertozzi said. The trial – funded by the U.S. government, the Gates Foundation and the South African government – will hopefully give us a better understanding of what the determinants of adherence are. The FACTS 001 trial, another tenofovir gel trial looking at safety and effectiveness, which has just begun in South Africa and uses a different dosing strategy from VOICE, should also provide clues.