Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study

Abstract

Background The Ring Study, a phase 3 trial in 1959 sexually active women (randomised 2:1), showed a favourable safety profile and a 31% HIV-1 infection risk reduction for a vaginal ring containing 25 mg of dapivirine, compared with a placebo ring. We report here the DREAM study, which aimed to evaluate safety, adherence, and HIV-1 incidence in those using the dapivirine vaginal ring (DVR) in open-label use. Methods The DREAM study is an open-label extension of The Ring Study, done at five research centres in South Africaand one research centre in Uganda. Former participants from The Ring Study, who remained HIV-negative and who did not discontinue the study due to an adverse event or safety concern that was considered to be related to the investigational product, were eligible. Women who were pregnant, planning to become pregnant, or breastfeeding at screening for DREAM were excluded. All participants received the DVR for insertion at the enrolment visit. Participants attended a 1-month follow-up visit and could either proceed with visits once every 3 months or attend monthly visits up to month 3 and then continue with visits once every 3 months. At each visit, HIV testing and safety evaluations were done, and residual dapivirine measured in used rings (approximately 4 mg is released from the DVR over 28 days of consistent use). HIV-1 incidence was compared descriptively with the simulated incidence rate obtained from bootstrap sampling of participants in the placebo group of The Ring Study, matched for research centre, age, and presence of sexually transmitted infections at enrolment. This study is registered with ClinicalTrials.gov, NCT02862171.

Vaginal ring acceptability: A systematic review and meta-analysis of vaginal ring experiences from around the world

“…The studies included 51 countries, with 28 studies from Europe [33,34,37,39,40,43,, 47 from North and South America and Australia [29-32, 36, 38, 42, 47, 48, 72-113], 18 from the Asia-Pacific [35,[114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129], 17 from North and sub-Saharan Africa [10,28,44,46,[130][131][132][133][134][135][136][137][138][139][140][141][142][143], and 13 from multiple regions [41,45,[144][145][146][147][148...…”

How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?

“…The frequency of NNRTI resistance in HOPE and DREAM was 7 of 38 seroconversions (18.4%) and 5 of 18 seroconversions (28%), respectively (Fig. 2) [69 ▪ ,77]. Both full-length reverse transcriptase Sanger sequencing and UMI-NGS with a detection limit of 1% mutation frequency were conducted due to the association of reduced susceptibility to DAPY class inhibitors by C-terminal domain mutations [78,79], but no additional or novel HIV-1 mutations were found to be selected by DPV.…”

“…A monthly silicone elastomer intravaginal matrix ring containing 25 mg of DPV (a diarylpyrimidine [DAPY] NNRTI) reduced the risk of HIV-1 infection among African women in the ASPIRE (MTN-020) and Ring (IPM 027) Phase III studies by 30% compared with placebo, and by an estimated 60% in the open label HOPE (MTN-025) and IPM DREAM studies [67,68 ▪ ,69 ▪ ,70]. Although the risk of breakthrough infection in younger women was greater in the trials due to low adherence, the open-label REACH (MTN-034) study showed higher rates of both ring acceptance (89%) and adherence (50%) in 16–21-year-old girls and young women.…”

Multipurpose Prevention Technologies: Opportunities and Challenges to Ensure Advancement of the Most Promising MPTs

“…Single indication HIV-only prevention products are also in development. Importantly, after multiple clinical trials demonstrating efficacy, the dapivirine intravaginal ring for HIV prevention is in the process of gaining regulatory approval in individual countries (27)(28)(29)(30). Furthermore, long-acting injectable cabotegravir (CAB-LA) has completed phase 3 trials in men who have sex with men, transgender women, and cisgender women, showing strong efficacy and safety results (31,32).…”