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Dapivirine Vaginal Ring Cuts HIV Risk
27% to 56% in Two Trials in African Women
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
A vaginal ring that slowly releases dapivirine, a nonnucleoside antiretroviral, significantly cut the risk of HIV infection in two large placebo-controlled trials that enrolled African women [1]. Estimated protection from HIV was highest in women older than 21, who usually adhered better to scheduled ring use. But HIV protection rates were lower than in some trials of daily tenofovir/emtricitabine (TDF/FTC) pills.
Preexposure prophylaxis (PrEP) has proved effective with daily or as-needed pills, if people take the pills regularly. Tenofovir vaginal gel lowered HIV risk in one trial of African women but not in another. In all successful and unsuccessful trials of TDF PrEP, good adherence proved critical to success. Interest in an antiretroviral-releasing vaginal ring runs high because, once a woman inserts the ring, adherence drops out of the equation unless she removes the ring (which happened infrequently in the African trials). A vaginal ring also ensures autonomy more than daily or as-needed pills.
CROI features reports of two randomized placebo-controlled trial of a vaginal ring containing 25 mg of dapivirine. The first trial, MTN-020 or ASPIRE, enrolled 2629 HIV-negative women between 18 and 45 years old in Malawi, South Africa, Uganda, and Zimbabwe. Women made monthly visits to get a new ring and counseling. Researchers collected vaginal samples quarterly to measure dapivirine levels. Adherence meant a dapivirine level above 95 pg/mL, a concentration almost always attained more than 8 hours after ring insertion [1].
Women in ASPIRE had a median age of 26 and follow-up reached a median of 1.6 years. A high proportion of women, 91%, attended monthly visits. About 80% of women randomized to dapivirine had detectable plasma levels of the drug.
During follow-up 168 women became infected with HIV, including 71 women assigned to dapivirine (incidence 3.3 per 100 person-years) and 97 assigned to placebo (incidence 4.5 per 100 person-years). Those numbers meant women using the dapivirine ring had a 27% relative reduction in HIV incidence (95% confidence interval [CI] 1 to 46, P = 0.046). In an analysis excluding two sites with lower retention and adherence, the relative risk reduction with dapivirine reached 37% (95% CI 12 to 56, P = 0.007). And among women older than 21, dapivirine users had a 56% lower HIV incidence than younger women (95% CI 31 to 71, P = 0.0003). Adherence was worse in women 18 to 21 than in older women.
ASPIRE result got published online by the New England Journal of Medicine [3] as researchers outlined results at a CROI press conference.
The IPM 027 RING trial enrolled 1959 women at six South African centers and one Ugandan center. Researchers randomized them in a 2-to-1 ratio to the dapivirine ring or a placebo ring. As in the ASPIRE trial, women were 18 to 45 years old and inserted a new ring every 4 weeks. Median age of the 1959 women stood at 25 and 91% of women were not married. At this presentation, 761 women (39%) had completed 2 years of follow-up.
During follow-up, 133 women picked up HIV infection, including 77 in the dapivirine arm (incidence 4.08 per 100 person-years) and 56 in the placebo group (6.10 per 100 person-years). Those results meant randomization to dapivirine lowered HIV risk 30.7% (95% CI 0.90 to 51.5, P = 0.0401). Among women older than 21, dapivirine cut HIV risk 37.5% (95% CI 3.5 to 59.5).
Product-related adverse events in IPM 027 included metrorrhagia, menometrorrhagia, pelvic discomfort or pain, suprapubic pain, and application site pain. In both trials adverse event rates were similar in the dapivirine and placebo arms.
A vaginal ring does nothing to protect women from anally transmitted HIV, but anal sex rates were low in both trials (2% in ASPIRE). A tougher question is why overall HIV protection rates in these two trials (27% and 31%) substantially lagged protection rates in trials of daily oral TDF/FTC in similar populations of African women and their male sex partners (75% in Partners PrEP [4] and 62% in the TDF2 study [5]).
The IPM 027 investigators proposed that the dapivirine ring "may be an important HIV prevention option for women at risk of HIV infection."
References
1. Baeten JM, Palanee-Phillips T, Brown ER, et al. A phase III trial of the dapivirine vaginal ring for HIV-1 prevention in women. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 109LB.
2. Nel A, Kapiga S, Bekker LG, et al. Safety and efficacy of dapivirine vaginal ring for HIV-1 prevention in African women. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 110LB.
3. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. February 22, 2016. DOI 10.1056/NEJMoa1506110. http://www.nejm.org/doi/full/10.1056/NEJMoa1506110
4. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399-410.
5. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423-434.
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