AVAC Says VOICE Trial Changes are Disappointing, But Do Not Close the Door on PrEP for Women
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 Results reported July 2010. Tenofovir 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 TDF/FTC reduced risk of HIV by an average of 73%. As a result, placebo arms discontinued 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. Results released July 2011. TDF/FTC 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. 2,400 injecting drug users Phase in Results Bangkok II/ Oral Bangkok, expected Tenofovir III TDF Thailand early 2012. Enrolling participants 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.
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.