MTN-003C and MTN-003D Fact Sheet

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The VOICE C and VOICE D Social and Behavioral Research Sub-studies: Looking for Answers about Adherence and the Women in VOICE

 

Making Sense of the Results of VOICE

VOICE –Vaginal and Oral Interventions to Control the Epidemic – was a major HIV prevention trial that tested the safety and effectiveness of two different approaches for preventing the sexual transmission of HIV in women: daily use of an antiretroviral (ARV) tablet (tenofovir or Truvada®) or daily use of a vaginal gel (tenofovir gel). VOICE (also called MTN-003) involved 5,029 women in Uganda, South Africa and Zimbabwe largely representative of the epidemic in sub-Saharan Africa; about half were under age 25, and most were not married.

Why are VOICE C and VOICE D important?

 

Absent a “gold standard” for measuring adherence, researchers have relied on multiple methods in hopes of being able to piece together as accurate a picture as possible about participants’ study product use during a trial. But, what does it mean when one measure suggests high adherence but another shows just the opposite, as in VOICE? Taken alone or in combination, current measures of adherence are not telling the full story.

 

As such, VOICE C and VOICE D are especially important for helping to make sense of the disparate findings in VOICE, by providing greater insight about the women’s attitudes and behaviors and their reasons for using or not using the products. Moreover, both studies will help in understanding women’s social contexts, perceptions about HIV risk and motives for taking part in VOICE, and the deterrents to both product use and being open about these difficulties with study staff.

 

What is learned in VOICE C and VOICE D may also suggest ways that HIV prevention trials can glean more accurate and meaningful information about product adherence, as well as help inform the development of products that women may find more practical and easier to use, and importantly, that they will actually use.

 

As with VOICE, both VOICE C and VOICE D are studies of the Microbicide Trials Network (MTN) and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH), both of the U.S. National Institutes of Health (NIH).

 

VOICE C at a Glance

VOICE D at a Glance

 

Fast Facts about Adherence in VOICE

Participants were counseled at each visit about the importance of adhering to the study regimens, product use and safe sex practices. Moreover, participants were informed of results of other studies that found the same products effective when used consistently, such as CAPRISA 004, which tested tenofovir gel used before and after sex, and the Partners PrEP Study, which evaluated daily use of Truvada and tenofovir tablets.

 

Several methods were used to measure adherence in VOICE. At different time points during the trial, study staff asked participants about their sexual activity, product use, male condom use and product sharing. Similar questions were asked privately through a computer program. In addition, a record was kept of the number of leftover pills and unused applicators for each participant at every monthly visit. After the study was completed, information collected through these measures was then collated with data from objective laboratory tests to detect the presence of drug in samples of participants’ stored blood, vaginal fluid and hair.

 

At the end of the study, an analysis of blood samples from a subset of 773 participants who had received the active products (including 185 women who acquired HIV) found adherence to product use was low across all groups. Drug was detected in less than a third of blood samples from women who were assigned to use either Truvada or oral tenofovir tablets and in less than a quarter of samples from women asked to use tenofovir gel. In sharp contrast, adherence was estimated to be about 90 percent based on self-report measures and monthly counts of unused gel applicators and leftover pills.

 

Younger, single women in VOICE were much less likely to use the study products than those who were older or married, and were also more likely to get infected. In the Truvada group, for example, drug was detected in the blood of just 21 percent of younger, single women compared to 54 percent for those older and married. HIV incidence, which reflects the number of women who become newly infected for every 100 participants in a given year, was 8.8 among young, unmarried women, more than 10 times higher than the HIV incidence of 0.8 for the older, married women in VOICE.

 

Researchers are analyzing every sample collected from all participants in VOICE – more than 160,000 plasma samples alone – to better understand the relationship between product use and product efficacy. The results of these analyses, which should be available sometime in 2014, are not likely to change the study’s main conclusions, however.

 

What is adherence?

 

Adherence – a person’s correct and consistent use of a prescribed regimen – is especially important in the context of HIV prevention clinical trials.

 

For instance, when adherence is high, meaning most participants use the study product as directed, researchers can determine with greater certainty whether the product prevents HIV.

 

But no matter how effective a given product or approach may be, it can have no benefit if it’s not used; women who need safe and effective HIV prevention methods must also be willing and able to use them. As such, a finding of low adherence in a clinical trial may provide important clues about what might happen in the “real world.”

 

Beyond VOICE: What Other Trials Have to Say

Partners PrEP and FEM-PrEP: The Highs and Lows of Adherence

Other studies in other populations of people have shown that with consistent use ARV-based products are highly effective for preventing HIV. Indeed, this was the basis for U.S. Food and Drug Administration approval of Truvada as HIV prevention, with the results of the Partners PrEP Study providing especially convincing evidence among heterosexual couples in whom one of the partners has HIV. Adherence to product use was very high in Partners PrEP, and both tenofovir and Truvada were very effective. Importantly, these were men and women who were on average older than the women in VOICE, and all were in committed relationships with a partner they knew was infected. They may have been more motivated to use the products consistently, knowing very well they risked getting infected. Yet, like VOICE, the FEM-PrEP study did not find Truvada effective among its population of young, predominately single women, most of whom had not followed the daily pill-taking regimen as instructed.

 

FEM-PrEP researchers are exploring the possible reasons why women had not used their study products, including whether participants hadn’t seen themselves at risk of HIV. Indeed, based on interviews with a small sample of participants at enrollment and quarterly throughout the time they were in the trial, the researchers found that 63 percent of the women perceived themselves at low or no immediate risk of HIV, yet, 28 percent had multiple partners and 74 percent reported having sex without a condom in the prior four weeks. The ongoing HIV testing and counseling and healthcare services that were provided as part of the study were important reasons the women enrolled and remained in the trial, and the researchers surmise that the reassurance of having a negative HIV test each month may have given these women an “out” for not using the product.

 

Aspiring to get it right:

Measuring adherence in current and future HIV prevention trials

Researchers are evaluating different strategies and new prevention approaches they hope women will want and be able to use. FACTS 001 is testing tenofovir gel used before and after sex and plans to enroll 2,900 women at nine South African sites, with results expected in 2015. As sister studies, ASPIRE, which is being conducted by the MTN, and The Ring Study, which is a trial of the International Partnership for Microbicides, are both assessing whether a vaginal ring containing the ARV drug dapivirine is safe and effective for protecting against HIV when used by women for a month at a time. Results of these two studies are expected late 2014 or early 2015.

 

Still, the results of VOICE have caused these and other trials to reevaluate and/or strengthen their efforts to enhance product adherence, including helping current and prospective trial participants and local communities better understand the importance of product use and the impact that non-adherence can have on the findings of a research study. Many of these trials have already incorporated ways to measure and use adherence information closer to “real time,” as the trial is underway. In ASPIRE, for example, participant blood samples are being tested on a routine basis to determine the presence of active drug, but in a way that preserves the blinded, placebo-controlled nature of the study. So, while the study investigators and participants don’t know individual participant results, data pooled according to sites or the study overall can indicate a need to modify ongoing adherence counseling, enrollment activities or community messages about ASPIRE.

 

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About VOICE

VOICE, also known as MTN-003, is a flagship study of the Microbicide Trials Network. The study began September 2009 and completed follow-up of all participants in August 2012. VOICE was led by Zvavahera Mike Chirenje, M.D., from the University of Zimbabwe in Harare; and Jeanne Marrazzo, M.D., M.P.H., from the University of Washington in Seattle. The study products were provided by Gilead Sciences, Inc., of Foster City, Calif., and by CONRAD, of Arlington, Va. Viread (oral tenofovir) and Truvada are registered trademarks of Gilead Sciences. In 2006, Gilead assigned a royalty-free license for tenofovir gel to CONRAD and the International Partnership for Microbicides of Silver Spring, Md. More information about VOICE and related sub-studies can be found at http://www.mtnstopshiv.org/news/studies/mtn003.

 

About the Microbicide Trials Network
The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners whose work is focused on the development and rigorous evaluation of promising microbicides – products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV – from the earliest phases of clinical study to large-scale trials that support potential licensure of these products for widespread use. More information about the MTN is available at www.mtnstopshiv.org.

 

Click here for PDF version of this document.

 

21-February-2014

 

See Also

MTN-003 (VOICE) Study Protocol

 

MTN-003C (VOICE C) Study Protocol

 

MTN-003D (VOICE D) Study Protocol

 

 


Source URL: https://mtnstopshiv.org/news/studies/mtn003cd/factsheet