Last updated on April 24, 2014 at 13:42 EDT

AVAC Says VOICE Trial Changes are Disappointing, But Do Not Close the Door on PrEP for Women

September 28, 2011

Continued PrEP research more important than ever

NEW YORK, Sept. 28, 2011 /PRNewswire-USNewswire/ — The announcement today that one arm of a large-scale HIV prevention trial known as VOICE will stop early is disappointing, but must be seen in context, according to the global advocacy organization AVAC. “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.

“As 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.

“VOICE remains a pivotal study. We commend the VOICE trial team, the members of the DSMB and especially the more 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. “While 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 various PrEP strategies in women have been reported. The data are mixed and require further investigation. See table of PrEP and microbicide trials below as well as at http://www.avac.org/trials/.

“Taken 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. “The 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.

“Medical 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. “There 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
                              Product                        Status/
       Trial       Phase       tested     Population        Findings
                                                          July 2010.
                                                          gel reduced
                              1%         889 women        risk of HIV
     CAPRISA     Phase       tenofovir   in South         infection by
     004         IIB         gel         Africa           39%.
                                         2,499 gay
                                         men and
                                         other men
                                         who have
                                         sex with
                                         men and
                                         transgender      Results
                                         women in         reported
                                         Brazil,          November
                                         Ecuador,         2010. TDF/
                                         Peru,            FTC reduced
                                         South            risk of HIV
                             Oral        Africa,          by an
                 Phase       TDF/        Thailand         average of
    iPrEx        III         FTC         and the US       42%.
                                                          Stopped for
                                                          futility in
                                         1,951            April 2011,
                                         heterosexual     with 28 HIV
                                         women in         infections
                                         Kenya,           in each arm.
                             Oral        South            Full results
    FEM-         Phase       TDF/        Africa and       expected
     PrEP        III         FTC         Tanzania         early 2012.
                                                          DSMB review
                                                          in July 2011
                                                          showed daily
                                                          TDF reduced
                                                          risk of HIV
                                                          by an
                                                          average of
                                                          62%; daily
                                                          reduced risk
                                                          of HIV by an
                                                          average of
                                                          73%. As a
                                                          placebo arms
                                                          but the
                             Oral        4,758            trial is
                             TDF         serodiscordant   ongoing.
                             and         heterosexual     Additional
                             oral        couples in       data
     Partners    Phase       TDF/        Kenya and        expected
     PrEP        III         FTC         Uganda           2013.

                                                          July 2011.
                                         1,219            reduced risk
                                         heterosexual     of HIV
                             Oral        men and          infection by
                 Phase       TDF/        women in         an average
    TDF2         II          FTC         Botswana         of 63%.
                                                          Oral TDF arm
                                                          dropped for
                             Oral                         futility
                             TDF,                         based on
                             oral                         data from
                             TDF/                         DSMB review.
                             FTC         5,029 women      Other arms
                             and         in South         continuing.
                              1%         Africa,          Full results
                 Phase       tenofovir   Uganda and       expected
    VOICE        IIB         gel         Zimbabwe         early 2013.
                                         drug users
                 Phase                   in               Results
     Bangkok     II/         Oral        Bangkok,         expected
     Tenofovir   III         TDF         Thailand         early 2012.
                 Open-       Oral        from iPrEx       Results
    iPrEx        label       TDF/        and ATN          expected
     OLE         extension   FTC         082              2013.
                                                          Expected to
                                         Will enroll      begin in Q4
                                         3,150            2011.
                              1%         women in         Results
    FACTS        Phase       tenofovir   South            expected
     001         III         gel         Africa           2013.

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

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 and other emerging HIV prevention options as part of a comprehensive response to the pandemic.


Source: PR Newswire