‘€œOf 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 thisstudy,’€ said Mitchell Warren, AVAC Executive Director. ‘€œThis 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.

‘€œAs the field grapples with what the different PrEP results mean, researchers, public health experts and communities must share information, discuss implications and determine the best way forward for these important interventions,’€ Warren said.

After an interim review of trial data, the independent Data Safety and Monitoring Board (DSMB) for VOICE’€”a five-arm proof-of-concept trial that has enrolled more than 5,000 women in South Africa, Uganda and Zimbabwe’€”has recommended that the oral tenofovir arm of the study be stopped and that the women in that arm exit the trial in a structured process. The DSMB concluded that there was no possibility that daily use of the oral tenofovir pill (TDF, brand name Viread) would show effectiveness in preventing HIV in the context of the VOICE trial. The trial will continue to evaluate two other antiretroviral-based products ‘€“ oral TDF/FTC (a combination of tenofovir and emtricitabine (FTC), brand-name Truvada) and 1% tenofovir gel. Importantly, the DSMB found no safety issues in any arm of the trial.

The data that form the basis for the DSMB’€™s recommendation were not released at the time of this announcement and will not be made available to the VOICE research team and public until data from all arms of the trial are analyzed when the trial is complete.

‘€œVOICE remains a pivotal study. We commend the VOICE trial team, the members of the DSMB and especially themore than 5,000 women who are participating in the trial. Despite the fact that oral tenofovir did not work in VOICE, two active arms of the trial are continuing and, importantly, no safety issues have been found,’€ said Warren. ‘€œWhile we don’€™t yet know why oral tenofovir did not work in this trial, VOICE will still provide critical information about both oral and topical PrEP that will help move the HIV prevention research agenda forward,’€ Warren said.

VOICE launched in 2009 with a five-arm trial design to evaluate the safety and effectiveness of oral tenofovir, oral TDF/FTC and 1% tenofovir gel, each used daily, compared to a placebo gel or placebo pill. The DSMB recommendation affects only the women in the oral tenofovir arm. While these women will exit the trial, participants in the other four arms will remain in the study.

In the last 18 months, there have been results from several trials of ARV-based prevention in HIV-negative people. So far, data from four effectiveness trials of variousPrEP strategies in women have been reported. The data are mixed and requirefurther investigation. See table of PrEP and microbicide trials below as wellas at  http://www.avac.org/trials/prep.)

‘€œTaken together, the data leave a range of questions on how oral and topical PrEP might be used as a prevention strategy for women. One of the most important questions to answer with urgency is which strategies will work for women throughout their lives, and VOICE will continue to be a key trial for answering this question,’€ Warren said. ‘€œThe different PrEP results we’€™ve seen in the past year underscore the need for close coordination of clinical trials testing the same or similar strategies and of planning for implementation,’€ Warren said, noting that plans were still underway to launch demonstration projects of oral TDF/FTC for HIV prevention among gay and bisexual men and transgender women, on the basis of the data from the iPrEx trial.

Additional information from VOICE, FEM-PrEP, Partners PrEP, iPrEx OLE, the FACTS 001 topical microbicide trial and planned PrEP demonstration projects will help guide decisions about the best use of oral and topical PrEP among different populations and will answer important questions about the potential for real-world use of PrEP among different populations and in different contexts.

‘€œMedical research is often complicated, and we must expect setbacks along the way. But with 2.6 million new HIV infections every year, it is imperative that we continue to look for new ways to curb the epidemic,’€ Warren added. ‘€œThere will never be a silver bullet for HIV prevention, so we must continue to rapidly expand testing, treatment and medical male circumcision, amongst the array of evidence-based interventions, while also accelerating the research and development of additional new options, notably oral PrEP, topical microbicides and vaccines to protect against HIV.’€

PrEP and ARV-Based Microbicide Trials

Trial

Phase

Product tested

Population

Status/Findings

CAPRISA 004

Phase IIB

1% tenofovir gel

889 women in South Africa

Results reported July 2010. Tenofovir gel reduced risk of HIV infection by 39%.

iPrEx

Phase III

Oral TDF/FTC

2,499 gay men and other men who have sex with men and transgender women in Brazil, Ecuador, Peru, South Africa, Thailand and the US

Results reported November 2010. TDF/FTC reduced risk of HIV by an average of 42%.

FEM-PrEP

Phase III

Oral TDF/FTC

1,951 heterosexual women in Kenya, South Africa and Tanzania

Stopped for futility in April 2011, with 28 HIV infections in each arm. Full results expected early 2012.

Partners PrEP

Phase III

Oral TDF and oral TDF/FTC

4,758 serodiscordant heterosexual couples in Kenya and Uganda

DSMB review in July 2011 showed daily TDF reduced risk of HIV by an average of 62%; daily TDF/FTC reduced risk of HIV by an average of 73%. As a result, placebo arms discontinued but the trial is ongoing. Additional data expected 2013.

TDF2

Phase II

Oral TDF/FTC

1,219 heterosexual men and women in Botswana

Results released July 2011. TDF/FTC reduced risk of HIV infection by an average of 63%.

VOICE

Phase IIB

Oral TDF, oral TDF/FTC and 1% tenofovir gel

5,029 women in South Africa, Uganda and Zimbabwe

Oral TDF arm dropped for futility based on data from DSMB review.  Other arms continuing. Full results expected early 2013.

Bangkok Tenofovir

Phase II/III

Oral TDF

2,400 injecting drug users in Bangkok, Thailand

Results expected early 2012.

iPrEx OLE

Open-label extension

Oral TDF/FTC

Enrolling participants from iPrEx and ATN 082

Results expected 2013.

FACTS 001

Phase III

1% tenofovir gel

Will enroll 3,150 women in South Africa

Expected to begin in Q4 2011. Results expected 2013.

More information about ongoing PrEP research is available at  avac.org/prep. More information about DSMBs is available at  avac.org/dsmb.

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About AVAC:    Founded in 1995, AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP andother emerging HIV prevention options as part of a comprehensive response tothe pandemic.