RESEARCH TRIANGLE PARK, NC — The Microbicides Trials Network (MTN) announced today that it will discontinue testing tenofovir vaginal gel in the HIV prevention trial VOICE (Vaginal and Oral Interventions to Control the Epidemic). This decision came after a routine review of study data on November 17, 2011. At that time, the VOICE Data and Safety Monitoring Board (DSMB) concluded that tenofovir gel was not effective at preventing HIV infection in the trial population.

This is the second recommendation within two months by the VOICE DSMB to discontinue a portion of the trial. On September 16, 2011, the DSMB determined that VOICE would not be able to show that oral tenofovir tablets were better than a placebo for preventing HIV infection among VOICE participants.

Now, the DSMB has also concluded that tenofovir gel will not demonstrate effectiveness in HIV prevention when compared with a placebo gel. The HIV incidence rates in the two groups were nearly identical, with a 6.1 percent incidence rate per year in the placebo gel group and 6.0 percent in the tenofovir gel group. Importantly, the DSMB had no concerns about the safety of tenofovir gel.

The VOICE trial will continue to evaluate the safety and effectiveness of oral Truvada® tablets compared to placebo tablets. Truvada is an HIV treatment product that contains a combination of the antiretroviral drugs tenofovir disoproxil fumarate (TDF, 300 mg) and emtricitabine (FTC, 200 mg) in a single pill. The DSMB recommended that the oral Truvada and placebo arms continue as originally planned. Women using Truvada or the oral placebo will stop using those products according to study protocol beginning in December 2011 or January 2012 through approximately June 2012. Final trial results are expected in early 2013.

The FEM-PrEP team commends the MTN and the VOICE researchers for their dedication to a rigorous scientific process and the trial participants for their important contributions to research on new HIV prevention methods. Despite these setbacks, VOICE remains a critically important study that will advance HIV prevention science.

The VOICE Trial: VOICE is a large Phase IIB HIV prevention trial involving 5,029 women at 15 sites in Uganda, South Africa and Zimbabwe. It is being conducted by MTN, which is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID). The trial is testing whether antiretroviral (ARV) medicines commonly used to treat people with HIV are safe and effective for preventing male-to-female sexual transmission of HIV. In VOICE, the safety and effectiveness of two different ARV-based approaches are being tested: daily use of an ARV tablet—an approach called oral pre-exposure prophylaxis (PrEP)—and daily use of a vaginal microbicide containing an ARV in gel form.

The FEM-PrEP Trial: As reported earlier, FHI 360 is closing its PrEP trial, FEM-PrEP, which is a Phase III, randomized, placebo-controlled clinical trial designed to assess the safety and effectiveness of a daily oral dose of Truvada for HIV prevention among women in sub-Saharan Africa. Following a scheduled interim review of the FEM-PrEP study data in April 2011, the trial's Independent Data Monitoring Committee advised that the FEM-PrEP study will be highly unlikely to demonstrate Truvada's effectiveness in preventing HIV infection in the study population, even if it continued to its originally planned conclusion.

FHI 360 subsequently concurred and initiated an orderly closure of the study over the subsequent few months. Follow-up of the HIV-negative cohort ended on August 12, 2011. Follow-up of women who became HIV-infected during the trial will continue until one year after their seroconversion, as per protocol, and they are referred for appropriate medical care and treatment in their community.

FEM-PrEP Next Steps: Data analyses from FEM-PrEP are not yet complete. Confirmation of all HIV infections, antiretroviral resistance testing and tenofovir and emtricitabine drug level testing is ongoing. Publication of the main findings, along with dissemination of final results to participants and site communities, is expected in the first quarter of 2012. Secondary analyses will occur later in 2012.

Comparison with FEM-PrEP and other trial results is crucial: The inability of the VOICE trial to demonstrate the effectiveness of oral tenofovir and tenofovir gel to prevent HIV infection is perplexing given that previous trials demonstrated positive findings when testing both these products.

In July 2010, scientists reported that the CAPRISA 004 trial of 1% tenofovir gel demonstrated 39% overall protection against HIV infection when women were asked to apply the gel before sex and a second time within 12 hours after sex (BAT 24 dosing regimen). In the VOICE trial, women were asked to apply tenofovir gel once a day, independent of sexual activity.

In clinical studies announced in 2011, researchers from the University of Washington (who conducted the Partners PrEP Study in Kenya and Uganda) and the U.S. Centers for Disease Control and Prevention (CDC) (who conducted the TDF2 study in Botswana) provided the first evidence that HIV infection among heterosexuals can be prevented by taking oral, once-daily Truvada or tenofovir tablets.

Even with the current VOICE findings, FACTS 001, a Phase III trial testing the same regimen of tenofovir gel used in CAPRISA 004, will continue as planned. FACTS 001 began enrolling participants in October and will involve approximately 2,200 women at up to nine sites in South Africa, with results expected in 2014.

With the closing of both the oral tenofovir and tenofovir gel arms of VOICE, there is now an even more critical need to explore why VOICE, CAPRISA, FEM-PrEP and the other trials had seemingly different findings. Investigators will only be able to determine why tenofovir gel was not effective in VOICE until the study is completed and all of the data are analyzed in full. As data become available, FHI 360 is eager to work with scientists from the MTN, CAPRISA, the University of Washington and the CDC to compare and understand results from recent HIV-prevention trials.