Monday, April 25, 2016

First Evidence of Long-Acting PrEP that May Work for Women

BETA is reporting from the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Boston—bringing you the latest news, updates, and research on HIV treatment and prevention.

A microbicide vaginal ring shows modest success in protecting women from HIV, but issues with adherence still remain.

Developing HIV prevention options for women at risk of HIV is an ongoing challenge for the HIV research community. Products controlled by women—such as microbicide gels that need to be applied daily or before and/or after sex—have failed to demonstrate efficacy in large clinical trials when women did not, or could not, use the products in the way they were designed. But now, there’s a glimmer of hope for a new type of HIV prevention product for women: a silicone vaginal ring that delivers a drug called dapivirine.
Annalene Nel
Annalene Nel, MD, PhD
“I’m thrilled to share that the dapivirine ring might be a new HIV prevention option for women,” said Annalene Nel, MD, PhD, of International Partnership for Microbicides, at a CROI press conference.
Nel, along with Jared Baeten, MD, PhD, of the University of Washington, presented groundbreaking results from two separate Phase 3 clinical trials (designed in collaboration) demonstrating the success of a long-acting dapivirine vaginal ring in reducing HIV risk among African women. Dapivirine is an investigational non-nucleoside reverse transcriptase inhibitor antiretroviral drug. The ring used in the two studies provided long-acting protection from HIV but needed to be replaced every 30 days.
The ASPIRE study, with 2,629 women in four African countries, showed an HIV risk reduction of 27% with the dapivirine ring compared to placebo. After researchers excluded two study sites with lower retention and adherence, the ring was responsible for reducing HIV risk by 37%. There were 168 HIV infections during the course of the study: 97 in the placebo group (4.5% incidence rate per 100 person-years) and 71 in the dapivirine group (3.3% incidence rate per 100 person-years).
The Ring Study, with 1,959 women in South Africa and Uganda, showed that the dapivirine ring reduced risk of HIV infection by 31%. Seventy-seven women (out of 1,300) using the dapivirine ring and 56 (out of 650) using placebo acquired HIV.
Jared Baeten
Jared Baeten, MD, PhD
“This is the first demonstration of a sustained release approach for antiretroviral prevention,” said Baeten at the CROI press conference.
Adherence was an issue
As with previous PrEP studies involving women, the results are tempered by adherence issues, which the researchers indicated may have been responsible for the modest (though significant) overall reduction in HIV risk seen.
Researchers were able to assess adherence by measuring the levels of dapivirine taken from blood samples and by measuring the amount of residual dapivirine still remaining on the vaginal rings once they’d been used.
In both studies, adherence increased over time—which Baeten and colleagues suggest could be due to the fact that women needed time “to be comfortable with the ring.” Women who were adherent and used the ring more consistently were more likely to have decreased risk of HIV infection.
Since participants self-inserted the vaginal rings during study visits, and returned with them still in place, Nel suggested during the press conference that some participants may have actually taken the rings out between visits then put them back in place before returning to the clinic. “The reason why many of the women at high risk participate in the trials—we should not underestimate. Women participate in trials for the standard of care as well as the monetary incentive.”
Younger women had less protection from HIV
Younger women were less likely to be adherent, and were thus less protected from HIV. In the ASPIRE study, the dapivirine ring did not show any evidence of protecting women between the ages of 18 and 21. However, the efficacy of HIV protection for women over 21 was 56%.
Nel reported similar findings in The Ring Study: no significant protection for women ages 18 to 21, but higher efficacy (37%) for women over age 21.
“HIV protection in the study was, not surprisingly, greater with greater adherence,” explained Baeten.
“The data from both studies suggest that the ring must be used consistently to achieve protection and that protection can be achieved with consistent use,” said Nel.
Baeten and colleagues also suggested that physiological considerations may have an effect. “The genital tract of women in this age group may be more susceptible to HIV-1 infection and potentially also more difficult to protect with antiretroviral prophylaxis strategies.”
Looking forward
Nel reported that the study sponsor, International Partnership for Microbicides, will pursue an open-label continuation of The Ring Study, and plans to seek regulatory approval for the investigational product.
During the press conference, Baeten raised the possibility that—if used in real-world settings—the ring might show greater risk reduction that that seen in these two studies.
“These clinical trials are tremendous endeavors. But they are different than what real-world counseling is like. Women in the studies are counseled, appropriately, that, ‘we don’t know if this works. We don’t know if this is safe.’ Perhaps it’s not surprising that we see lower adherence and lower HIV protection in these two studies. I think the real-world situation might be quite different, when someone is choosing to use the ring that is known to be safe and effective.”
Baeten, J. M. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women.The New England Journal of Medicine. February 22, 2016.
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