The VOICE Study: Vaginal and Oral Interventions to Control the Epidemic
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Overview
The VOICE Study – Vaginal and Oral Interventions to Control the Epidemic – is a major HIV prevention trial evaluating two different approaches for preventing the sexual transmission of HIV in women, looking at whether some of the same antiretroviral (ARV) medications commonly used to treat people with HIV are safe and effective for HIV prevention, as either a vaginal microbicide or an oral tablet. In addition, VOICE , which is also known as MTN-003, seeks to determine which of these routines women are more likely to follow: taking a tablet daily, an approach known as oral pre-exposure prophylaxis (PrEP), or applying a vaginal microbicide gel daily. VOICE is the first effectiveness study of a microbicide that women use every day and the only trial evaluating both a tablet and a microbicide gel in the same study.
Specifically, VOICE is testing two different ARV tablets – tenofovir (Viread®) and Truvada® – drugs that are routinely used as part of combination therapy for treating HIV; and an ARV-based candidate microbicide called tenofovir gel. The study, which began September 2009, completed enrollment of 5,029 sexually active HIV-negative women at sites in Zimbabwe, Uganda and South Africa in June 2011. Results are expected early 2013.
VOICE is being conducted by a team of researchers working in the Microbicide Trials Network (MTN), an HIV/AIDS clinical trials network established and funded in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all components of the U.S. National Institutes of Health (NIH).
Why the VOICE Study is Important
Between 70 and 90 percent of all HIV infections in women are acquired through heterosexual intercourse. Moreover, women are twice as likely as their male partners to acquire HIV during sex. Although HIV infection rates are beginning to decline in some parts of the world, sub-Saharan Africa continues to bear the burden of the epidemic, with 22.5 million people living with HIV – more than two-thirds of the total 33.3 million cases globally. Because women and girls are especially vulnerable, there is an urgent need for effective prevention strategies. Two promising strategies involve the use of anti-HIV drugs, as either a vaginal gel or an oral tablet. Because VOICE is evaluating both approaches, it can provide greater understanding about their safety and effectiveness than can individual studies. Moreover, VOICE is uniquely positioned to provide important information about which approach women are more likely to use. This is critical, because no method can ever be effective if women don’t use it. Importantly, results of VOICE will help determine if tenofovir gel can be approved as a method for preventing HIV among women.
The VOICE Study at a Glance
- VOICE is a Phase IIb trial testing two different HIV prevention approaches – a tablet (PrEP) and a vaginal gel.
- Women who enrolled have been randomly assigned to one of five study groups, either to one of the three tablet groups: tenofovir, Truvada, or oral placebo (a tablet that looks the same but has no active medicine); or to one of the two gel groups: tenofovir gel or placebo gel. VOICE was designed to enroll approximately 5,000 women, about 1,000 in each group. Enrollment of 5,029 women was completed in June 2011.
- Women use the same product every day for the entire study (about two years), but no one knows which tablet or gel.
- Because it is not known whether the study approaches will be effective, researchers do everything possible to help prevent women from acquiring HIV. All participants receive ongoing HIV risk-reduction counseling, condoms and diagnosis and treatment of STIs – standard measures for reducing the risk of HIV.
- Protocol Chairs are Zvavahera Mike Chirenje, M.D., Zimbabwe; and Jeanne Marrazzo, M.D., M.P.H., USA.
Participant Safety and HIV Monitoring
VOICE was designed according to the most rigorous international medical practice and ethical standards and incorporates a multi-tiered safety review process designed to protect the safety and well-being of all participants. Potential volunteers were carefully screened by study staff to ensure that only women for whom it would be medically safe to participate could enroll. Women who joined the study are closely monitored during the entire time they are in the study. A detailed and ongoing informed consent process ensures that participants understand the procedures, risks and benefits of the study, and that they are not obliged to participate and may leave the study, without consequence, at any time.
All women in VOICE receive comprehensive HIV prevention counseling and services, with free condoms, risk-reduction counseling, monthly HIV testing and other provisions, throughout the trial. Despite these intensive efforts, a woman could become infected if she has unprotected sex with a partner who has HIV. Researchers don’t know if or to what extent drug resistance might occur in women who become infected in the study, so several safeguards are in place to minimize any potential risk. For instance, women in VOICE are tested for HIV at every monthly visit. If a test indicates that a woman has acquired HIV, staff will take steps to immediately stop her use of study product, because its continued use can increase the chance that virus will become resistant to the drug. VOICE participants who acquire HIV are counseled by study staff and linked with appropriate services and care in their communities. These women are encouraged to remain in VOICE to continue with routine study visits and be monitored for resistance so that it can be managed appropriately by those treating the infection. In addition, site staff offer women the opportunity to participate in another MTN study, MTN-015 . As a long-term observational study, MTN-015 does not provide HIV treatment, but frequent laboratory tests indicating how the disease is progressing and how women are responding to treatment can help local treatment providers better manage the clinical care of these women.
The Products Being Studied
The Vaginal Gel: The active ingredient in tenofovir gel belongs to a class of ARVs called nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). In its oral form, tenofovir disoproxil fumarate (TDF), known by the brand name Viread, is approved as a treatment for HIV infection in combination with other medications. Tenofovir gel is not a treatment for HIV; it is an approach being evaluated for its potential ability to prevent the sexual transmission of HIV. Laboratory and nonclinical studies have demonstrated that tenofovir gel acts on certain cells of the vagina and cervix that are the primary targets for HIV infection. Clinical safety studies performed to date have found it is well-tolerated and safe. More recently, the CAPRISA 004 study found tenofovir gel was safe and reduced the risk of HIV by 39 percent among women who used it before and after vaginal sex compared to women who used a placebo gel. CAPRISA 004 involved 889 women at two sites in South Africa. A larger trial of the same regimen, called FACTS 001, will be taking place at seven sites in South Africa. In the meantime, the U.S. Food and Drug Administration has indicated that it will consider approving tenofovir gel as an HIV prevention method for women based on the results of CAPRISA 004 and VOICE, if they are favorable.
The ARVs:Tenofovir and Truvada , the brand name for a combination drug consisting of tenofovir and emtricitabine (FTC), are NRTIs approved for the treatment of HIV. They are widely prescribed and well-tolerated by most people. In the VOICE Study, participants assigned to use tenofovir or Truvada are given the same dose used for treating HIV. Three PrEP trials have recently reported results, indicating that the drugs are both safe and effective in those populations studied. In the iPrEx Study, which involved nearly 2,500 men who have sex with men, there were 44 percent fewer HIV infections among participants assigned to daily use of Truvada compared to the placebo group. The Partners PrEP Study evaluated the safety and effectiveness of both tenofovir and Truvada among men and women in a discordant relationship with a partner who is HIV-positive; 4,758 serodiscordant couples were enrolled. There were 62 percent fewer HIV infections among participants assigned to take tenofovir daily compared to participants who took a placebo tablet, and 73 percent fewer infections among those who took Truvada. In a smaller trial of 1,200 heterosexual men and women in Botswana, researchers from the U.S. Centers for Disease Control and Prevention found 62.6 percent fewer HIV infections occurred in the group assigned to take Truvada than in the placebo group. A fourth study, FEM-PrEP, is preparing to close earlier than originally planned, because an interim review by its independent data monitoring committee established that even if the study were to continue, it would not be able to conclude whether or not daily Truvada is effective for prevention of HIV in its study population of high-risk women.
Viread, the brand name for tenofovir, and Truvada are registered trademarks of Gilead Sciences, Inc., of Foster City, Calif., U.S. Gilead assigned a royalty-free license for tenofovir gel to CONRAD, of Arlington, Virginia, and the International Partnership for Microbicides of Silver Spring, Maryland, in 2006. For VOICE, Gilead is providing tenofovir and Truvada tablets free of charge, and CONRAD is providing both the gel and gel applicators at no cost.
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About the MTN
The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH). The MTN brings together international investigators and community and industry partners who are devoted to reducing the sexual transmission of HIV through the development and evaluation of products applied topically or administered orally, working within a unique infrastructure specifically designed to facilitate the research required to support licensure of these products for widespread use.
Based at the University of Pittsburgh and Magee-Womens Research Institute in Pittsburgh, Pennsylvania, USA, MTN’s core operations are supported by a network laboratory at the University of Pittsburgh, a statistical and data management center housed within the Statistical Center for HIV/AIDS Research & Prevention (SCHARP) at the Fred Hutchinson Cancer Research Center, and FHl 360, a global organization with expertise conducting clinical protocols. MTN conducts its trials at clinical research sites located in seven countries and spanning three continents. MTN receives its funding from three NIH institutes: NIAID, the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Among the groups developing and evaluating microbicides for HIV prevention globally, the MTN is the only one funded by NIH. More information about the VOICE Study and other MTN studies can be found at http://www.mtnstopshiv.org/news/studies/mtn003 .
9-August-2011
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