BOSTON — Women who used a dapivirine vaginal ring for HIV prevention were infected at a rate of less than 2%, according to interim data from the concurrent HOPE and DREAM extension trials.
What this drop in incidence means in the context of oral HIV prevention drugs and the rollout of test-and-treat programs remains to be seen, but one thing is true: “This is the lowest HIV rate ever seen in a prevention cohort like this,” said Jared Baeten, MD, from the University of Washington in Seattle, who is lead investigator of the HOPE open-label extension trial.
And by “cohort like this,” he means women. Historically, the oral HIV prevention combination of tenofovir and emtricitabine (Truvada, Gilead Sciences) has been proven effective in women only in trials that enroll women as one member of a serodiscordant couple (N Engl J Med. 2012;367:399-410). Women-only trials were halted because participants were not using the drug enough to draw any conclusions (N Engl J Med. 2012;367:411-422 and 2015;372:509-518).
Phase 3b HOPE results were presented by Baeten here at the Conference on Retroviruses and Opportunistic Infections (CROI) 2018. They are a follow-up to the ASPIRE phase 3 randomized controlled trial — presented at CROI in 2016, as reported by Medscape Medical News — which showed an overall efficacy of 27% (N Engl J Med. 2016;375:2121-2132).
A HOPE and a DREAM
Of the women who participated in ASPIRE, 57% agreed to move on to the HOPE study, which will be completed at the end of this year.
For the first 3 months, the 1407 HOPE participants — from Malawi, South Africa, Uganda, and Zimbabwe — came to the clinic monthly to exchange their rings for new ones. After that, they made quarterly visits.
At each visit, the women surrender their used ring and are given the option to decline future rings. As of October 2017, when the interim data were analyzed, 98% percent of women had showed up for their 9-month clinic visit, and 81% continued to accept the ring.
Baeten and his colleagues examined the returned rings and determined that 89% had residual drug concentration levels consistent with at least some use. In ASPIRE, this rate was 77%.
Women remain hugely at risk for HIV.
There is no placebo group — having one when researchers know the ring is effective “would be unethical” — so although the HOPE study is not designed to assess the effectiveness of the ring, the number of women who acquire HIV is reported, Baeten told Medscape Medical News.
According to interim data, 12 women acquired HIV, for an HIV incidence rate of 1.9%. In contrast, the rate in ASPIRE was 4.5%.
Baeten and his team calculated — with a modeling study that used historic data — that, in the absence of the ring, 4.1% of the HOPE women would have acquired HIV. If those assumptions are accurate, the dapivirine ring reduces the incidence of HIV by 54%, which is far higher than the 27% overall efficacy seen in ASPIRE.
In the DREAM trial, which is following 815 women from South Africa and Uganda who previously participated in The Ring Study (N Engl J Med. 2016;375:2133-2143), the same ring and the same drug is being tested. Interim DREAM data also show an efficacy rate of 54%.
The consistency between the two trials “is something that’s quite important,” said Zeda Rosenberg, ScD, from the International Partnership for Microbicides in Silver Spring, Maryland, who presented the interim DREAM data. “We are encouraged by these data, because we always thought that women would likely use the ring more once they knew the results of the phase 3 trial. That has been seen in other open-label extension studies of oral PrEP.”
It is possible that the ring is even more effective than these results suggest. The interim data have not been broken down by how much dapivirine had leeched from the ring. When the studies are complete and the researchers correlate HIV protection with how much of the ring was used, we will have a better sense of how effective the ring can be with regular use, said Rosenberg. Those data are expected to come out in 2019.
The data were met with excitement by some meeting attendees.
“It’s great to see some choices other than oral PrEP emerging,” said Sheena McCormack, MBBS, from Chelsea and Westminster Hospital in London, who is principal investigator of the PROUD oral PrEP study (Lancet. 2016;387:53-60).
These findings are “very encouraging,” said Peter Godfrey-Faussett, MBBS, from UNAIDS in Geneva. “Here is the next step for ring development.”
“Women remain hugely at risk for HIV, particularly in southern and east Africa. Until recently, there have been very few options in control of women to use,” he told Medscape Medical News. “We’ve seen, at this conference, that HIV incidence is sometimes falling among men because women are taking more antiretrovirals and pass on less HIV, and men can get circumcised. What we need now are interventions for women that they can use to reduce their risk of HIV.”
But it is this rapidly shifting HIV incidence rate that motivated some attendees to advise caution.
Epidemiology and Caution
After the presentation, Baeten was asked whether the roll out of test-and-treat strategies could have lowered the local incidence rate. If it did, the 54% rate of protection attributed to the ring might not be accurate.
“You have to be cautious of overly interpreting the results, because they may not be that significant,” said Reuben Granich, MD, an independent public health consultant in Washington, DC.
In fact, because the HOPE women did not acquire HIV when they used the ring in ASPIRE and because all those women have aged during the trials, it is not a fair parallel to compare the results in HOPE with those from the placebo group in ASPIRE, said Carl Dieffenbach, PhD, from the National Institutes of Health (NIH), which funded the HOPE study. They might be at different risk than the women who did acquire HIV in ASPIRE.
“We purposefully looked at adherence in this study and, over time, it morphed into a study of a measure of incidence,” Dieffenbach explained. When you do a clinical trial, you draw the control group “from the same pool at the same time” to capture the real risk that everyone in that community faces.
Although Baeten and Rosenberg drew parallels between HOPE and DREAM and the open-label extension trials for the oral HIV prevention pill, the one big difference is that, in the iPrEx extension (Lancet Infect Dis. 2014;14:820-829), researchers gathered dried blood spots from participants to check for drug levels so they could accurately correlate adherence with efficacy, he pointed out. Because the ring is topical and the drug does not circulate in the blood stream, researchers assessing the ring can’t do that.
Still, Dieffenbach reiterated the commitment of the NIH to support the development of the ring through licensure, and reported that the agency is currently funding the development of a vaginal ring containing both dapivirine and a hormonal contraceptive.
Future Commitments
“It is our hope and dream,” Dieffenbach said, chuckling, “that the study does get a fair hearing by regulators.”
Granich agreed, saying that despite what he sees as the studies’ limitations, the results are still exciting.
“As we head toward the elimination and end of AIDS, these prevention methods are going to be really, really important — especially as we go the last mile,” he told Medscape Medical News.
HOPE was funded by the National Institutes of Health. DREAM received funding from the Danish Ministry of Foreign Affairs, Flanders Department of Foreign Affairs, Irish Aid, the German Federal Ministry of Education and Research, PEPFAR, USAID, and the Bill and Melinda Gates Foundation. The International Partnership for Microbicides provided the study drug to both trials. Baeten, Rosenberg, McCormack, Godfrey-Faussett, and Granich have disclosed no relevant financial relationships.
Conference on Retroviruses and Opportunistic Infections (CROI) 2018: Abstracts OA143LB and 144LB. Presented March 7, 2018.
Follow Medscape on Twitter @Medscape and Heather Boerner @HeatherBoerner
Tidak ada komentar:
Posting Komentar