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Dapivirine Vaginal Ring Does Not Blunt Effectiveness of Hormonal Contraception
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Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle
WEBCAST:http://www.croiwebcasts.org/console/player/33461?mediaType=slideVideo&
Mark Mascolini
Using a dapivirine vaginal ring to prevent HIV infection did not diminished the effectiveness of hormonal contraception in the ASPIRE/MTN-020 trial in 4 African countries [1]. Regardless of randomization to dapivirine or placebo, pregnancy incidence proved high among women taking oral contraceptives but low in those using injectable or implantable hormonal contraceptives.
A vaginal ring containing the nonnucleoside dapivirine lowered the rate of HIV acquisition by 31% in a placebo-controlled trial in Africa [2]. Because the potential for drug-drug interactions between the dapivirine ring and hormonal contraceptives had not been assessed in epidemiologic studies, ASPIRE/MTN-020 investigators compared pregnancy incidence in women randomized to the dapivirine ring or to placebo in trial participants.
ASPIRE/MTN-020 enrolled women from 4 sub-Saharan countries [3]. Participants were HIV-negative, sexually active, not intending to become pregnant, and using a highly effective contraception method. Researchers conducted monthly urine pregnancy tests and collected plasma samples quarterly. They calculated pregnancy incidence separately for each of four hormonal contraceptive methods: oral contraceptive pills, implants, injectable norethisterone enanthate (NET-EN), or injectable depot medroxyprogesterone acetate (DMPA).
The analysis included 2310 women, 1139 randomized to dapivirine and 1171 to placebo. Age ranges were similarly distributed in the two study arms (about 20% 18 to 21, about 33% 22 to 26, and about 45% 27 to 45). About 60% in each study arm reported using a condom the last time they had vaginal sex, and 16% in each arm had more than 1 sex partner in the past 3 months.
There were 63 pregnancies in the dapivirine arm (5.5%) and 54 in the placebo arm (4.6%). In an analysis adjusted for age, marital status, number of prior live births, and condom use, pregnancy incidence did not differ between dapivirine and placebo users. Overall pregnancy incidence proved much higher among women taking oral contraceptives (about 30 per 100 person-years regardless of randomization) than in women using an implant, NET-EN, or DMPA (all about 1 per 100 person-years). The difference between the oral group and the other groups was just as striking when the analysis accounted for dapivirine detection at quarterly follow-up visits.
The researchers suggested that poor pill adherence could explain the high pregnancy rate in oral contraceptive users. In contrast, injectable and implantable methods proved highly effective in preventing pregnancy in both the dapivirine and placebo arms. Thus the researchers conclude that the dapivirine ring is "not associated with diminished hormonal contraceptive effectiveness for pregnancy prevention." These findings reflect in vitro studies showing that dapivirine does not induce the CYP1A2 or CYP3A4/5 drug-metabolizing enzymes. The ASPIRE team observes that topical absorption of dapivirine eluted from the ring yields low systemic dapivirine concentrations, which cut chances of interactions between dapivirine and other drugs.
The researchers believe their findings "support the use of the dapivirine vaginal ring for HIV-1 prevention" in women using contraception.
References
1. Balkus J, Palanee-Phillips T, Siva S, et al. Dapivirine ring use does not diminish the effectiveness of hormonal contraception. Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle. Abstract 88. http://www.croiwebcasts.org/console/player/33461?mediaType=slideVideo&
2. Nel A, van Niekerk N, Kapiga S, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med. 2016;375:2133-2143.http://www.nejm.org/doi/full/10.1056/NEJMoa1602046
3. ClinicalTrials.gov. Phase 3 safety and effectiveness trial of dapivirine vaginal ring for prevention of HIV-1 in women (ASPIRE). ClinicalTrials.gov identifier NCT01617096. https://clinicaltrials.gov/ct2/show/NCT01617096
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