The VOICE Study: Vaginal and Oral Interventions to Control the Epidemic
Overview
The VOICE Study – Vaginal and Oral Interventions to Control the Epidemic – is a major HIV prevention trial evaluating two different approaches for preventing sexual transmission of HIV in women, looking at whether some of the same antiretroviral (ARV) medications used successfully for the treatment of HIV are safe and effective for HIV prevention, as either a vaginal microbicide or an oral tablet. In addition, the VOICE Study, which is also known as MTN-003, seeks to determine which of these routines women are more likely to follow: taking a tablet by mouth once a day, an approach known as oral pre-exposure prophylaxis (PrEP), or applying a vaginal microbicide gel every day. VOICE is the first effectiveness study of a microbicide that women use every day and the only trial evaluating both a gel and a tablet 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, will enroll approximately 5,000 sexually active HIV-negative women at sites in Zimbabwe, Uganda, South Africa and Malawi.
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, due in part to biological factors that make them more susceptible. With HIV infection rates continuing to rise in many areas of the world and the majority of new HIV infections occurring among women in sub-Saharan Africa, 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 the safety and effectiveness of each than individual studies could. Moreover, VOICE is uniquely positioned to provide important information about which approach women are more likely to use. This is critical, because no method will be effective if women don’t use it.
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 enroll are randomly assigned – like the toss of a coin – 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 will involve 5,000 women, 1,000 in each group.
- 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 – proven 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 are carefully screened by study staff to ensure that only women for whom it would be medically safe to participate can enroll. Women who join the study are closely monitored during the entire time they are in the study. A detailed 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 a comprehensive HIV prevention package, 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 immediately stop her use of study product, because its continued use can increase the chance that virus will become resistant to the drug. VOICE Study participants who acquire HIV will be counseled by study staff and linked with appropriate services and care in their study site communities. Women are encouraged to remain in VOICE to continue with routine study visits and be monitored for resistance so that if identified, it can be managed appropriately by those treating the infection. In addition, site staff will 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, 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 show that tenofovir gel can prevent HIV infection of target cells in vaginal tissue. Clinical safety studies performed to date have found it is well-tolerated and safe. 
The ARVs: Tenofovir and Truvada, the brand name for a combination drug consisting of tenofovir disoproxil fumarate 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 will be given the same doses of tenofovir and Truvada used for treating HIV. Oral PrEP studies thus far suggest these drugs are safe to be used in clinical trials involving people not infected with HIV.
Truvada and both the oral and topical formulations of tenofovir were developed by Gilead Sciences, Inc., of Foster City, California, USA, which assigned a royalty-free license for the topical gel to the International Partnership for Microbicides of Silver Spring, Maryland, and CONRAD, of Arlington, Virginia, in December 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 Family Health International, 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.
14-July-2010
See Also
Sep 16, 2009
Jul 20, 2009
