Marcia Frellick

February 22, 2016

BOSTON — A vaginal ring inserted monthly that slowly releases the potent antiretroviral dapivirine reduced the risk for HIV infection by up to 56% in the phase 3 multicountry ASPIRE study of African women.

And in the Ring Study — a phase 3 sister study of women in sub-Saharan Africa, funded by the International Partnership for Microbicides (IPM), which developed the ring — it was shown to be safe and effective in preventing the transmission of HIV during vaginal intercourse.

"The results are encouraging," said ASPIRE researcher Jared Baeten, MD, PhD, vice chair of the Department of Global Health and codirector of the International Clinical Research Center at the University of Washington in Seattle.

"For the first time, we have two studies in women demonstrating that a female-controlled strategy can safely reduce the risk of acquiring HIV," he told Medscape Medical News.

Findings from both studies were released here at the Conference on Retroviruses and Opportunistic Infections 2016. Results from ASPIRE — A Study to Prevent Infection with a Ring for Extended Use — which was funded by the National Institutes of Health, were published online in the New England Journal of Medicine to coincide with their presentation.

ASPIRE

Dr Baeten and his colleagues recruited women 18 to 45 years of age in Malawi, South Africa, Uganda, and Zimbabwe. The 2629 healthy, sexually active, HIV-negative women were randomized to receive either the dapivirine ring or a placebo ring, which was inserted once every 4 weeks over 24 months.

 
For the first time, we have two studies in women demonstrating that a female-controlled strategy can safely reduce the risk of acquiring HIV.
 

There were 168 HIV-1 infections during the study period — 71 in the dapivirine group (incidence, 3.3 per 100 person-years), and 97 in the placebo group (incidence, 4.5 per 100 person-years).

There was a 27% relative reduction in the overall incidence of HIV-1 in the dapivirine group, compared with the placebo group (95% confidence interval [CI], 1 - 46; P = .046). But when the researchers excluded two sites that had lower rates of retention and adherence, the relative reduction was 37% (95% CI, 12 - 56; P = .007). And when they limited the analysis to women older than 21 years, the relative reduction was 56% (95% CI, 31 - 71; P = .0003).

Rates of adverse medical events and antiretroviral resistance among women who became infected were similar in the two groups.

Ring Study Had Similar Results

In the Ring Study, Annalene Nel, MD, PhD, from Paarl, South Africa, who is chief medical officer of the IPM, and colleagues assessed the safety and efficacy of the ring in 1959 women from six research centers in South Africa and one center in Uganda.

The primary efficacy end point was the rate of HIV-1 seroconversion, and the primary safety end point was the incidence of adverse events.

The 1762 South African women and the 197 Ugandan women were randomized, in a 2 to 1 ratio, to receive either the dapivirine ring or a placebo ring.

The median age at the start of the study was 25 years, and 91% of the women were unmarried.

During the study period, there were 133 HIV-1 infections — 77 in the dapivirine group (incidence, 4.08 per 100 person-years) and 56 in the placebo group (incidence, 6.10 per 100 person-years).

The risk for HIV-1 infection was 30.7% lower in the dapivirine group than in the placebo group (95% CI, 0.90 - 51.5; P = .0401). When the researchers limited the analysis to women 21 years and older, the risk was 37.5% lower (95% CI, 3.5 - 59.5).

Although HIV clinicians were hoping for larger reductions in risk, "it's very comforting to see how consistent the results are across the two trials," said Sheena McCormack, MD, a clinical epidemiologist from Chelsea and Westminster Hospital in London, United Kingdom.

 
If you put tenofovir in the ring, would we have seen better results?
 

It is difficult to know whether improving the ring itself or the medicine it releases would make for higher numbers, she told Medscape Medical News. "If you put tenofovir in the ring, would we have seen better results?"

Dr McCormack said she is not surprised that adherence was low among the youngest women in the trial. For one thing, adherence is more difficult in a study like this where the women didn't know whether they had drug or placebo.

"Also, the women are not necessarily in relationships where things, such as when they're going to have sex, are predictable," she explained. They also don't have as great a sense of their risk as older women, she pointed out.

One of the next steps in the research is an open-label trial where women will know they are using the ring and not a placebo, Dr Nel said.

"We've seen in the other prevention trials with an open-label extension that efficacy improved because the women knew it was safe and effective. We hope we will see the same," she said.

Dr McCormack noted that she is encouraged by the results and glad to hear that the IPM plans to apply for licensure.

If licensure is granted, it is estimated that the vaginal ring will be on the market in 2019, Dr Nel told Medscape Medical News.

Dr McCormack reports receiving support from Gilead Sciences. Dr Nel is chief medical officer of the IPM. Dr Baeten has disclosed no relevant financial relationships.

Conference on Retroviruses and Opportunistic Infections (CROI) 2016: Abstracts 109LB and 110LB. Presented February 22, 2016.

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