The VOICE Study: Vaginal and Oral Interventions to Control the Epidemic
I. The Big Picture
1. What is the aim of the VOICE Study?
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) medicines used successfully for treatment of HIV are safe and effective for HIV prevention, as either a vaginal microbicide gel or an oral tablet. In addition, the VOICE Study, which is also known as MTN-003, seeks to determine which of these regimens women are more likely to follow: applying a vaginal gel daily or taking a tablet by mouth once a day, an approach known as oral pre-exposure prophylaxis (PrEP). VOICE is the first effectiveness study of a microbicide that women use every day. Moreover, VOICE is the only trial evaluating both a tablet and a gel in the same study. VOICE will involve approximately 5,000 HIV-negative women between the ages of 18 and 45 from communities in southern Africa where a woman’s risk for acquiring HIV through sexual intercourse is among the highest.
2. Why is this study important?
VOICE is a trial focused on sexually active women in sub-Saharan Africa, a population representative of the largest and fastest growing sector affected by the world-wide epidemic. 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. Women desperately need a method for preventing HIV that they can control themselves. ARV-based prevention is a promising approach.
3. Who is conducting the study?
The VOICE Study 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 Division of AIDS (DAIDS) at 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). Leading the study are Zvavahera Mike Chirenje, M.D., University of Zimbabwe, Harare, Zimbabwe; and Jeanne Marrazzo, M.D., M.P.H., University of Washington, Seattle, Washington, USA. As co-sponsors of the trial, CONRAD of Arlington, Virginia, USA; and Gilead Sciences, Inc., of Foster City, California, USA, are providing the study products free of charge.
4. Where is the VOICE Study being conducted?
The VOICE Study is being conducted at NIAID-funded clinical research sites in Malawi, South Africa, Uganda and Zimbabwe.
5. Why is VOICE only being conducted in Africa?
The MTN has clinical trial sites in Africa, India and the United States, but not all of these sites are in places where the rates of new HIV infections are as high as they are in Africa. In places where the risk for HIV infection is high, researchers can determine more quickly and with greater certainty that a certain product is working. More importantly, women in sub-Saharan Africa represent the largest and fastest growing at-risk population for HIV, and they have the most to gain if this trial or any other trial identifies a safe and effective method for preventing HIV.
6. When did the trial begin and how long will it last?
VOICE began enrolling women into the study in September 2009 and is expected to take about three and a half years to complete. Results should be available some time in 2012.
7. What is a microbicide?
Microbicides are substances designed to prevent or reduce the sexual transmission of HIV or other sexually transmitted infections (STIs) when applied topically inside the vagina or rectum. A microbicide can be formulated in many ways, such as a gel or cream, or as a ring that would release the active ingredient over time. Several microbicide products are being tested in clinical trials, including in trials being conducted by the MTN, although none is currently approved or available for use.
8. What is pre-exposure prophylaxis (PrEP)?
Pre-exposure prophylaxis, or oral PrEP, is an experimental HIV prevention approach that involves use of ARVs by people who are HIV-negative. The idea is that by taking a medicine routinely – daily, for example –HIV infection would be prevented if a person were exposed to the virus, such as through unprotected sex.
9. What microbicide is being studied in the VOICE Study?
The VOICE Study is evaluating a candidate vaginal microbicide called topical tenofovir gel, which is among a newer class of candidate microbicides with specific activity against HIV. Tenofovir gel contains the same ingredient that is in the oral tablet, which is approved as a treatment for HIV infection in combination with other drugs. In its current form, each dose of tenofovir gel contains approximately 40 mg of active drug. Laboratory and animal 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 the gel to be well tolerated and safe. An expanded safety and acceptability trial called HPTN 059 found daily use of the gel over six months by sexually active HIV-negative women was safe and well-tolerated. Side effects experienced by women in these previous trials were minor and included dryness, itching, burning or discomfort in the genital area.
10. What ARVs are being tested in VOICE?
VOICE is evaluating two ARV tablets, tenofovir and Truvada®. The full name for tenofovir is tenofovir disoproxil fumarate (TDF) and is known by the brand name Viread®. Truvada is the brand name for a combination drug that contains tenofovir and another active ingredient called emtricitabine (FTC). Sometimes researchers refer to Truvada as TDF+FTC. Tenofovir and Truvada are approved for the treatment of HIV when used in combination with other ARVs, a regimen called antiretroviral therapy (ART). They belong to a class of anti-HIV medications called nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) that act against HIV by targeting a key enzyme the virus needs to copy its genetic material – an essential step for the virus to multiply and infect other cells inside the body.
Participants in the VOICE Study will be given the same daily doses of tenofovir and Truvada used for treating HIV. Tenofovir is a 300-mg tablet. A single Truvada tablet contains 300 mg of tenofovir and 200 mg of FTC. Both drugs have excellent safety profiles and are well tolerated by most HIV-infected people. In some, minor side effects can include upset stomach, dizziness, headache, joint pain or fever. Serious side effects are rare, but can include liver function problems, kidney damage or failure, or reduction in bone mineral density. Much less is known about the safety and side effects of these drugs in people without HIV, but a study conducted by Family Health International in HIV-negative women in Ghana, Cameroon and Nigeria found no serious side effects, including to the liver, kidney or bone, associated with daily use of tenofovir. Of 859 participants for whom safety information was received, some noted stomach discomfort and headache.
11. Who manufactures the study products?
Gilead Sciences, Inc., of Foster City, California, USA, developed all three study products. While the company continues to manufacture tenofovir and Truvada, it assigned a royalty-free license for the vaginal gel to the International Partnership for Microbicides of Silver Spring, Maryland, and CONRAD, of Arlington, Virginia, in December 2006.
12. How is the VOICE Study designed?
VOICE is a Phase IIb (proof of concept) trial designed to evaluate both the safety and effectiveness of two approaches for preventing the sexual transmission of HIV: daily use of an ARV tablet (tenofovir or Truvada) and daily use of an ARV-based gel (tenofovir gel). To learn about the safety and effectiveness of each
approach requires the kind of trial in which participants are randomly assigned by chance, like in a raffle, to different study groups, including groups that may use a placebo. VOICE has five study groups -- two gel groups (tenofovir gel and an inactive placebo gel) and three tablet groups (tenofovir, Truvada and an inactive placebo tablet) – and will enroll approximately 5,000 women, about 1,000 in each group. The study is “blinded,” so neither participants nor researchers know who is in which tablet or gel group. Women in the two gel groups are provided identical applicators pre-filled with either tenofovir gel or placebo gel, although both gels look identical. Each study participant randomized to the tablet regimen takes two tablets once a day, one that looks like tenofovir and one that looks like Truvada. One contains the oral dose of the drug to which the participant is assigned and the second is an inactive placebo tablet. All participants receive ongoing HIV risk reduction counseling, condoms, and diagnosis and treatment of sexually transmitted infections (STIs). Once enrolled, participants will be in the study, on average, for 24 months.To determine the approach that women are more likely to use consistently, researchers ask participants a series of standard questions about sexual activity, product use, product use adherence, male condom use and product sharing. Participants also answer the same kinds of questions privately with the help of a computer, an approach that is thought to be a better way to collect sensitive information.
13. What kind of approvals were needed before this study could get underway?
VOICE underwent extensive and rigorous review by NIAID and the U.S. Food and Drug Administration. Moreover, before any site can begin enrolling women into the study, approvals must be received by government and regulatory authorities in the trial site country and by the site’s Institutional Review Board (IRB) or Ethics Committee (EC). IRBs and ECs ensure that studies are scientifically valid and ethically sound and provide oversight throughout the duration of the trial.
14. How does this trial differ from other HIV prevention trials of microbicides or PrEP?
The VOICE Study is the only trial evaluating two HIV prevention approaches – a tablet and a gel – in the same study and is the first effectiveness trial of a microbicide that women use every day instead of only at the time of sexual intercourse. VOICE is also one of the first trials of a newer class of microbicides, so-called ARV-based gels, that have specific action against HIV. While most other ongoing or planned trials of oral PrEP are testing either tenofovir or Truvada, only VOICE and the Partner’s PrEP Study are evaluating both.
15. How is the VOICE Study different from CAPRISA 004, which also involves tenofovir gel?
CAPRISA 004 is a Phase IIb trial that was conducted by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) to assess the safety and effectiveness of tenofovir gel for preventing HIV infection in women who applied the gel within 12 hours prior to sex and as soon as possible within 12 hours after sex during the 12-18 months they were in the study. In VOICE, women in the gel groups are applying study product once a day, whether they have sex or not, and will remain in the study for an average of two years. And while CAPRISA enrolled 892 sexually active HIV uninfected women at two sites in South Africa, VOICE is a larger study of 5,000 women, testing not only tenofovir gel but also oral tenofovir and oral Truvada. VOICE will enroll women from multiple regions in South Africa and from Malawi, Uganda, Zambia and Zimbabwe. Despite these differences, the two studies complement one another, and each is critical to advancing our understanding about the safety and effectiveness of tenofovir gel using different strategies among different populations of African women, as well as for providing insight about the particular regimen women in Africa will be more likely to use.
16. What is the reason for using the gel everyday in VOICE?
VOICE was designed in accord with current understanding about the mechanisms of tenofovir. As such, researchers conducting VOICE believe that using gel every day will provide cells with a sufficient level of drug needed for continuous protection. That’s because for the drug to work against HIV it must be in its activated form, which requires the drug first getting inside a target cell and then adding to its structure two molecules called phosphates. It takes tenofovir a bit of time to forge this protective shield, and the protection it offers gradually subsides. Researchers see daily dosing as a way to supply cells with a steady stream of reinforcements, providing a sustained defense impenetrable against HIV.
17. Why evaluate oral and topical approaches to HIV prevention in the same study?
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. Yet, it is not enough to determine that these strategies will be safe and effective for protecting against sexual transmission of HIV. Understanding which approach women are more likely to use is also critical, because no method will be effective if women don’t use it. A single trial designed to evaluate both approaches can provide the greatest insight and the most scientifically reliable information about the effectiveness, safety and women’s preferences for each.
18. Why is the VOICE Study using two drugs for oral PrEP but only one gel?
MTN researchers consulted many experts, including a group convened by NIAID’s Division of AIDS, to help determine whether the VOICE Study should evaluate as oral PrEP tenofovir only, Truvada only, or both drugs. Consensus weighed heavily in favor of studying both drugs, because this would allow researchers a unique opportunity to better assess their safety and effectiveness in an important at-risk population. The same decision was reached by University of Washington researchers, who are conducting the Partners PrEP Study, testing both drugs against a placebo in serodiscordant couples, whereby one partner is HIV infected and the other is not. Because the gel formulation of Truvada is not considered ready for testing in humans, it is only possible in VOICE to study tenofovir gel.
19. How will results of other oral PrEP or microbicide trials affect the VOICE Study?
New information from other oral PrEP or microbicide trials may influence the conduct of the VOICE Study. The VOICE Study team will consider all relevant research results as they become available and make modifications to the study as needed.
20. What if the products prove to be effective?
Should the VOICE Study provide evidence for the effectiveness of tenofovir, Truvada and/or tenofovir gel in preventing HIV infection, it will be critical to provide study participants, their communities, and the worldwide population at risk for HIV infection access to the effective product(s) in a timely manner. Product manufacturers are considering licensing agreements and preferred pricing arrangements for the study communities and other resource-poor settings. In addition, NIAID and MTN will initiate discussions with other public and private funding sources such as the World Health Organization, UNAIDS, Bill & Melinda Gates Foundation, and appropriate site government agencies that may be able to purchase product supplies in bulk and offer them at low or no cost to the study communities and other resource-poor communities most in need of the product(s).
II. At the Trial Site
21. Do women participating in the study provide informed consent?
Women who volunteer to join the study are told about all the study procedures, any possible risks and benefits and the time requirements of the study. Study staff also explain that women do not have to join and they can leave the study at any time, without consequence. This process is called “Informed Consent” and it occurs prior to screening for the study and again at enrollment, and continues throughout the study. Information is provided in simple terms and translated into local languages. Site community educators and Community Advisory Board (CAB) members also play important roles in helping prospective participants understand the study.
22. What is being done to ensure the safety of participants in the VOICE Study?
VOICE was designed according to the most rigorous international medical practice and ethical standards and includes numerous measures to protect the well-being of its 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. Although the ARVs being used in VOICE are usually safe and cause few side effects when used as part of treatment in HIV-infected people, there is much less information about their use in people without HIV. As such, VOICE researchers will monitor study participants very closely throughout the trial. Several other layers of review and monitoring of safety are incorporated into the trial, including strict national and international procedures for monitoring and reporting. This involves clinical teams at the trial sites who perform thorough checks on the health, safety and welfare of participants at each study visit; a team at the MTN statistical and data management center (SDMC) that assesses incoming reports on a daily basis; and a VOICE protocol safety review team (PSRT) that provides regular monthly oversight. The PSRT includes three additional MTN physicians – two specializing in infectious diseases and HIV and the other in obstetrics and gynecology – whose sole responsibilities are to ensure that everything possible is being done to monitor and protect the safety of participants.
As the study progresses, regular reviews will be conducted by an independent Vaccine and Prevention Data and Safety Monitoring Board (DSMB) that oversees clinical trials funded by NIAID to ensure that participants are not being adversely affected by the study or study products. If the DSMB has any safety concerns, it may, at any time, recommend that the study modify its procedures or be discontinued. In addition, the DSMB may recommend halting the trial if there is compelling evidence for a product’s effectiveness or if it becomes clear that the trial cannot answer whether a product is effective.
23. What happens if a participant acquires HIV during the VOICE Study?
All women in VOICE receive a comprehensive HIV prevention package, with free condoms, risk-reduction counseling, 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. Women in the trial who test positive for HIV are taken off study product immediately, because continuing its use could increase the risk of the virus becoming resistant to that drug; and they are counseled and referred by study staff to local HIV care and support services. Providers and programs to which participants are referred offer psychosocial services and medical care, including antiretroviral therapy. Women are encouraged to remain in the VOICE Study and continue with routine study visits. When possible, they also are referred to other local research studies for HIV-infected women. In addition, VOICE Study participants who become infected are invited to participate in another MTN study called MTN-015, a long-term observational study of women who acquire HIV while participating in an MTN trial. Although MTN-015 does not provide HIV treatment, with a participant’s permission, researchers can maintain close contact with her primary treatment provider and share results of laboratory tests that are performed as part of the study, which may suggest modifications to her treatment and help improve the level of care.
24. How could a woman acquire HIV while taking part in a trial of a microbicide or oral PrEP, approaches meant to prevent HIV?
In sub-Saharan Africa, where the VOICE Study is being conducted, a woman’s risk for acquiring HIV through sexual intercourse is greater than in any other part of the world. To reduce the risk of HIV for women participating in its trials, MTN researchers provide trial participants free condoms, frequent HIV testing and HIV risk-reduction counseling, including on the use of condoms, and routine testing and treatment for STIs. Despite these intensive, ongoing efforts, a woman who participates in a trial like VOICE could acquire HIV if she has unprotected sex with a partner who is infected with the virus.
25. Is there concern that women who become HIV-infected will develop drug resistance to either tenofovir or Truvada?1
It’s important to understand that drug resistance would be possible only in someone infected with HIV, and the study’s primary interest is in reducing the risk of HIV infection in all women who participate. If, despite the study’s efforts a woman becomes infected, VOICE has safeguards to minimize the potential for drug resistance. 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. Women testing positive for HIV in VOICE will be monitored for resistance so that if identified, it can be managed appropriately by those treating the infection. Resistance to one ARV does not reduce the effectiveness of all ARVs. Most types of drug resistance can be readily managed by stopping the ineffective ARV drug and starting a new combination of drugs. Still, researchers don’t know if or to what extent drug resistance might occur in women who become infected in the study. VOICE and similar studies will provide important information.
26. What is the VOICE Study doing to reduce the risk of drug resistance?1
VOICE includes several safeguards to minimize the potential for drug resistance. Researchers screen all prospective participants for HIV infection to avoid enrolling anyone who is already HIV-infected, and women who are enrolled undergo monthly HIV testing so that investigators can quickly identify women who have acquired HIV and immediately stop their use of the study drug (tablet or gel). In addition, study products are dispensed monthly – and only after results of HIV testing are known to be negative – to prevent an infected participant from continuing to use the study product. This is especially important as neither the researchers nor the participants know if the study product they were randomly assigned to use contains an active drug or a placebo. Based on current understanding about viral resistance, VOICE researchers believe that these and other procedures will help minimize the potential that resistant virus will develop or persist in women who acquire HIV while in the study.
27. How will you know if a woman has drug resistance?1
Women who acquire HIV infection in VOICE will be tested often for the presence of HIV drug resistant virus using both standard and highly sensitive methods. Women who chose to participate in MTN-015 will have additional tests for resistance performed so that researchers can determine its prevalence and patterns over time. Tests that are performed as part of MTN-015 may suggest modifications to her treatment and help improve the level of her care.
28. Does VOICE provide antiretroviral therapy, or ART, to women who acquire HIV?
MTN receives funding to conduct clinical trials only, and therefore, is not adequately resourced to provide HIV treatment. However, MTN investigators have given a great deal of thought to the issue of providing ART to women who acquire HIV during study participation. VOICE Study participants who acquire HIV are be linked with appropriate services and care in their study site communities. 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.
29. The VOICE Study includes a lot of monitoring of bone health. What does that have to do with HIV prevention?2
Researchers have observed that HIV-infected women who are treated with an ART regimen that includes tenofovir can experience modest decreases in bone mineral density (thinning of bone). If tenofovir and Truvada are to be considered approaches for preventing HIV it will be important to understand the effects, if any, on bone in women who are otherwise in good health. It is especially important to gain understanding of the potential effects on women in sub-Saharan Africa who are among those at highest risk for acquiring HIV. As such, all participants in the VOICE Study undergo regular monitoring to assess how product use may be affecting bone. In addition, a separate, more focused study on bone health, called VOICE B, is being conducted at two VOICE sites in a subset of VOICE participants who have been randomly assigned to the oral tablet regimen.
30. Are you concerned that participants in the study will feel a false sense of protection and be more apt to engage in high-risk behaviors?
Participants are counseled at each visit on the importance of adhering to the regimens of the study and safe sex practices. They are also reminded that none of the products being tested has been proven effective in preventing HIV, and that not all women participating in the study may be using an active product.
31. ARVs are in short supply for HIV-infected individuals, so aren’t you concerned participants will share or sell study products?
Study products are dispensed only to enrolled participants upon receipt of a written prescription from an authorized prescriber, and each prescription is limited to a one-month supply of tablets or gel. Participants are counseled monthly on the importance of adhering to study regimens and on the dangers posed by sharing study products with other participants or others not in the study, especially since not all women will be assigned to use active products.
32. How do you know that women are really using the gel or taking the tablets everyday? And what kind of barriers might prevent women from fully complying with study regimens?
VOICE researchers recognize the importance of understanding women’s adherence to daily regimens of vaginal gel and oral tablets, because not even the most effective prevention approach can do any good if it’s not used. Adherence is evaluated using different measures, such as counts of tablets or gel applicators at monthly visits, face-to-face interviews and with Audio-Computer Assisted Self Interviewing (ACASI), which allows participants to answer sensitive questions about condom use, product use and sexual behavior with greater privacy. In addition, VOICE researchers hope to identify other important social, cultural and contextual factors that operate at the household, study clinic and community levels that may influence VOICE participants’ willingness or ability to adhere to the study product use regimen. As a sub-study of VOICE, VOICE C will explore these additional factors and the level at which they may hinder or facilitate adherence.
33. What happens to women who are breastfeeding or who become pregnant?
Pregnant women and women who are breastfeeding cannot join the VOICE Study because researchers don’t know the effects of tenofovir, Truvada or tenofovir gel on a woman’s pregnancy or the development of her fetus, or on her baby if she uses the gel or tablets when breastfeeding. Women also must not be planning to become pregnant during the study, and those who enroll must use effective contraception and have monthly pregnancy tests throughout the trial. If a participant becomes pregnant during the study, she must stop using the study products, but will remain in the study and continue with all trial site visits. She will also be referred by study staff to available sources of medical care and other services that she or her baby may need. Depending on the timing of pregnancy relative to the study’s progress, some women may be able to resume using gel or tablets, provided they are no longer breastfeeding. Women who become pregnant will also be invited to participate in MTN’s Prevention Agent Pregnancy Exposure Registry, also known as EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure), which is a first-of-its-kind observational study of women who become pregnant during an HIV prevention trial as well as women who during their pregnancy, participated in an MTN safety study in pregnant women.
34. What are the medical benefits for women participating in the study?
Study participants receive free laboratory tests and physical exams, counseling on preventing HIV infection and free condoms. STI risk-reduction counseling, testing and treatment are provided at no charge to both women and their partners. In addition, VOICE provides effective contraception and monthly pregnancy and HIV testing. Participants who acquire HIV during the trial are counseled appropriately and receive referrals to community-based programs for care and support. They have the option to remain in the trial off of study product and be followed with all scheduled safety evaluations.
35. If women participating in this study use condoms, how will you know if the gel or ARV is effective for preventing HIV?
In order to reduce the risk of HIV for all women in the trial, researchers provide participants free condoms and HIV risk-reduction counseling, including on the use of condoms, and routine testing and treatment for STIs. If,during the course of the study, every single participant used a condom for every act of sexual intercourse, it would be nearly impossible for researchers to evaluate the effectiveness of microbicides or oral PrEP. But as is true in the “real world,” women are not always able to convince their partners to use condoms or to use them all the time. Once the study is completed, results are analyzed taking into account the number of times women reported using condoms with each sex act.
36. How does the VOICE Study involve the community?
The MTN is guided by an agenda that seeks to foster participation by and collaboration with representatives of diverse scientific disciplines related to HIV prevention, as well as from the lay communities in which MTN trials are being conducted. MTN’s Community Advisory Boards (CABs) play an essential role, as do community and advocacy groups, in every stage of protocol development and implementation. MTN’s Community Working Group (CWG), comprised of community educators and CAB members from each clinical research site, is particularly engaged, and for VOICE, has provided input on the protocol, informed consent process and many of the study’s procedures. The MTN also sought consultations with leading African advocates working in HIV prevention, treatment access and women’s health. The MTN leadership acknowledges that an understanding of the purpose, methods, and limitations of clinical research is vital for meaningful community input into study design and implementation, and that true community participation in HIV prevention research requires a level of ownership in the entire research process. As such, all trials sites have active community engagement programs with local non-governmental organizations, activist groups, journalists, local physicians, health department officials and other stakeholders. These activities involve locally designed approaches and methods to make the science clearly accessible to lay people, including those with little or no formal education.
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More information about the VOICE Study can be found at http://www.mtnstopshiv.org/news/studies/mtn003
1 Additional information about HIV drug resistance in ARV-based prevention is available at http://www.mtnstopshiv.org/node/1075
2 – A Q&A and backgrounder on VOICE B, the Bone Mineral Density Sub-study of VOICE, can be found at http://www.mtnstopshiv.org/news/studies/mtn003
14-July-2010
See Also
Sep 16, 2009
Jul 20, 2009
