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Safety of dapivirine vaginal ring and oral PrEP
for HIV prevention in the second trimester.
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Dapivirine Vaginal Ring for PrEP Safe Through Second and Third Trimesters
CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver
Mark Mascolini
Results from the third of three cohorts in the DELIVER (MTN-042) phase 3 trial confirmed the safety of the dapivirine vaginal ring when used as preexposure prophylaxis (PrEP) throughout the second and third trimesters of pregnancy [1]. The Microbicide Trials Network, which conducted the trial, says researchers "believe there is now sufficient evidence that the dapivirine ring is safe to use to protect against HIV throughout pregnancy, when the risk of acquiring HIV is up to three times greater than at any other time" [2].
Earlier randomized trials established dapivirine ring safety before pregnancy and during early pregnancy [3] and when started between 30 and 35 weeks gestation or 36 or more weeks gestation [4]. Using the ring before pregnancy did not affect pregnancy incidence, distribution of pregnancy outcomes, or frequency or pattern of congenital anomalies [3]. Late in pregnancy dapivirine did not affect rates of adverse pregnancy outcomes compared with tenofovir/emtricitabine (TDF/FTC), adverse outcomes were rare, and no maternal or infant serious adverse events could be linked to either PrEP method [4].
The DELIVER cohort described at CROI 2024, cohort 3, enrolled women at 12 to 29 weeks gestation, with ultrasound used to confirm gestational age [1]. Whereas the first two DELIVER cohorts used the dapivirine ring for 4 to 6 weeks and 7 to 12 weeks of pregnancy, the third cohort wore the ring for up to 30 weeks of pregnancy. To enter cohort 3, women had to be 18 to 40 years old and having a singleton pregnancy. They could have no history of pregnancy complications. Researchers randomized participants in a 4-to-1 ratio to dapivirine or TDF/FTC.
Researchers enrolled 251 women in Malawi, South Africa, Uganda, and Zimbabwe and randomized 202 to dapivirine and 49 to TDF/FTC. Age averaged 25.7 in the dapivirine group and 24.0 in the TDF/FTC group. Among women randomized to dapivirine, 70% had a prior pregnancy (average 1.6 full-term births), compared with 53% in the TDF/FTC group (average 1.5 prior full-term births). Overall time from enrollment to delivery averaged 16.4 weeks and ranged from 8 to 29.1 weeks.
Among 200 women analyzed in the dapivirine group, 197 (99%) had live births, as did 48 of 48 women in the TDF/FTC group. Respective proportions of full-term births were 95% and 94%. Among women using the ring, there were 2 stillbirths or intrauterine fetal deaths (judged not related to the ring) and 1 spontaneous abortion. No one taking TDF/FTC had these outcomes, and no one in either group had a therapeutic abortion.
For the dapivirine ring and TDF/FTC, rates of any hypertensive disorder of pregnancy measured 9% and 14%, peripartum or antepartum hemorrhage 3% and 0%, and postpartum hemorrhage 1% and 0%. These rates are similar to local background frequencies established by systematic chart review.
While 12% of women using the ring had composite (mother and infant) adverse events, 8% using TDF/FTC had composite events. Respective rates of composite events among infants were 16% and 4%. No mother in either study arm died, but 1 infant of a mother using the ring died. No women became infected with HIV. Congenital anomalies affected 9 infants (5%) in the dapivirine group and 2 (4%) in the TDF/FTC group.
The researchers noted that this analysis included only uncomplicated singleton pregnancies in urban or periurban settings and did not have the statistical power to detect rare pregnancy complications.
Combined with results from DELIVER cohorts 1 and 2, these cohort 3 findings, the researchers proposed, "support using the dapivirine vaginal ring and TDF/FTC as prevention options for pregnant people at risk of HIV."
References
1. Mhlanga F, Bunge KE, Fairlie L, et al. Safety of dapivirine vaginal ring and oral PrEP for HIV prevention in the second trimester. CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver. Abstract 168.
2 Microbicide Trials Network. Study finds no safety concerns when the dapivirine vaginal ring is used during the second and third trimesters of pregnancy, according to results presented at CROI 2024. Press release. March 5, 2024.
3. Makanani B, Balkus JE, Jiao Y, et al. Pregnancy and infant outcomes among women using the dapivirine vaginal ring in early pregnancy. J Acquir Immune Defic Syndr. 2018;79:566-572. doi: 10.1097/QAI.0000000000001861. https://journals.lww.com/jaids/fulltext/2018/12150/
pregnancy_and_infant_outcomes_among_women_using.5.aspx
4. Bunge K, Balkus JE, Fairlie L, et al. DELIVER: a study of a dapivirine vaginal ring and oral PrEP for the prevention of HIV during pregnancy. J Acquir Immune Defic Syndr. 2024;95:65-73. doi: 10.1097/QAI.00000000. https://journals.lww.com/jaids/abstract/2024/01010/deliver__a_safety_study_of_a_dapivirine_vaginal.9.aspx
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