Results from a large-scale HIV prevention trial among African women known as VOICE (Vaginal and Oral Interventions to Control the Epidemic) provide an urgent reminder that products must meet the needs of the people using them.
While disappointing, the results lend new urgency and direction to the search for additional safe and effective HIV prevention options for women, AVAC said today.
Researchers announced today that none of three pre-exposure prophylaxis (PrEP) and microbicide interventions tested in VOICE – daily oral tenofovir, daily oral TDF/FTC (Truvada), and daily 1% vaginal tenofovir gel – provided additional protection against HIV in the study, likely because few of the women in the trial used the products as directed.
This low adherence explains the lack of benefit and is consistent with data from other antiretroviral (ARV)-based prevention trials that found a correlation between higher levels of adherence and protection from HIV. The new results were presented in Atlanta at the 20th Conference on Retroviruses and Opportunistic Infections (CROI).
“The VOICE results reinforce what we already know from previous trials – these interventions work when they are used, and they don’t work when they are not used,” said Mitchell Warren, AVAC Executive Director. “PrEP is still a valuable option for many women, and men, who recognize their risk and can take PrEP consistently. Now we have a dual responsibility to understand who might benefit from daily PrEP and ensure that they can access it, and to accelerate the development of additional options that can meet the urgent needs of others.”
A range of trials has shown varying levels of effectiveness of tenofovir-based prevention for heterosexual men and women, and for men and transgender women who have sex with men.
The VOICE data do not invalidate the prior trial results, including the finding that daily oral tenofovir-based PrEP provided high levels of protection for women in stable relationships where one partner was HIV-positive, and that 1% vaginal tenofovir gel was modestly effective on a different dosing schedule.
“Previous trials of tenofovir-based gel and pills have shown that biologically this approach can work, but only if the product is used. HIV prevention is never just biomedical – behavior is key. What we’ve learned from VOICE and other trials is that adherence to the prescribed dose – the behavioral component – is the variable that determines effectiveness,” Warren added.
“Biomedical tools do not work in a vacuum but rather in the complex realities of women’s and girls’ lives. The women of VOICE and other prevention trials have much to tell us. Now we need to listen to what they are saying and design prevention options based on a better understanding of their reproductive and sexual health needs and desires, their perceptions of personal risk for HIV infection, and their interest in and ability to use the products offered in those trials,” Warren said.
VOICE showed a very high incidence of HIV in the trial – 5.7 percent among all the women in the trial and 8.8 percent among unmarried women under the age of 25 in South Africa.
“The high rates of new HIV infections among women, especially young women, are the most shocking and disturbing data from this trial. They are a sobering reminder of how desperately women need new prevention options that they can and will use to protect themselves from HIV,” said Elizabeth Bukusi, Deputy Director (Research and Training) of the Kenya Medical Research Institute (KEMRI) and an AVAC Board Member. “The VOICE results teach us again that an urgent need for new prevention options does not mean women will automatically demand or use those products.”
Following the 2012 US Food and Drug Administration (FDA) approval of Truvada as PrEP for adults at risk of HIV, AVAC called for a comprehensive package of PrEP demonstration projects for all populations – including young women – that could benefit from the proven option of daily oral TDF/FTC.
Demonstration projects and other studies in which participants know that they are taking an intervention that has been proven to work will provide important information about how adherence can be supported in real-world situations.
AVAC is also working with advocacy partners in the US and internationally to push national health agencies to systematically determine how PrEP can be delivered to the women and men who will benefit from it.
This includes a statement released today from a coalition of HIV and women’s health advocates calling on US agencies to coordinate a PrEP agenda to quickly and accurately answer questions about how PrEP can be made available to women in the US.
At the same time, AVAC calls for accelerated research and development of additional HIV prevention options that are less dependent on adherence and may be easier and more desirable for women to use.
These include different delivery mechanisms, such as long-acting rings and injections, and less-than-daily dosing schedules, such as that being tested in the FACTS 001 trial, which is looking at 1% tenofovir vaginal gel used around the time of sex.
Renewed commitment and resources are also urgently needed for research to develop HIV vaccines, which would overcome many of the issues around adherence, and combined contraceptive and HIV prevention methods, which would address many women’s needs more comprehensively.
“The data presented today are only the beginning of what we will learn from VOICE. We need to make sure that we get all of the information we can from the VOICE participants to help us understand why women were dedicated to the trial and yet were not willing or able to use the products consistently. These women are at such high risk for HIV, we owe it to them to work with them to find the options that they can and will use to protect themselves,” Warren said.