Extended duration dapivirine vaginal ring shows promise for HIV prevention
The use of a 90-day extended duration vaginal ring containing 100 or 200 mg of the antiretroviral drug dapivirine appeared safe, effective, and acceptable among HIV-negative women, according to results of a phase I trial presented at CROI 2021.
“Extended duration rings achieved higher dapivirine concentrations compared with monthly dapivirine rings which is likely to translate into at least equal efficacy,” said study author Dr Albert Liu from the San Francisco Department of Public Health, San Francisco, California, US. “All three vaginal rings were well tolerated.”
“Our findings support further evaluation of 3-month dapivirine rings for HIV prevention in women,” he said.
Participants in the MTN-036/IPM-047 trial were 49 HIV-negative cisgender females aged 18–45 years (mean age 30 years, 39 percent White) who were enrolled at two sites in the US. They were randomized 1:1:1 to receive extended duration dapivirine vaginal rings containing either 100 or 200 mg dapivirine to be used continuously for 13 weeks, or monthly rings containing 25 mg dapivirine to be replaced every 4 weeks.
Blood and cervicovaginal fluid (obtained through vaginal swabs) samples were obtained at 1, 2, and 4 hours after ring insertion and removal, and at each of the eight follow-up visits, and cervical tissue biopsies obtained at day 28 and 91.
The proportion of participants who experienced grade ≥2 genitourinary adverse events (AEs) did not significantly differ between the 100 or 200 mg rings (6 percent in each group) compared with the 25 mg monthly vaginal ring group (12 percent; p=1.00). Similarly, grade ≥3 AEs did not significantly differ between the extended duration and monthly vaginal ring groups (p=1.00). [CROI 2021, abstract 147]
A total of 126 AEs were reported, 76 percent of which were unrelated to the rings. Most AEs were mild (79 percent) or moderate (21 percent) in severity, and only one grade 3 AE was reported (unrelated to study product).
Geometric mean Tmax ranged from 16–25 days in plasma and 1–7 days in cervicovaginal fluid. The decrease in dapivirine concentrations in both plasma and cervicovaginal fluid 4 hours after ring removal did not significantly differ between groups.
Dapivirine concentrations were 1.3–1.9 times higher in plasma and 1.5–2.9 times higher in cervicovaginal fluid with the extended duration vs monthly rings.
The Area Under the Concentration-Time Curve for days 0–28 was 1.5–2.00 times higher for the extended duration vs the monthly ring.
Dapivirine concentration in cervical tissue was consistently higher with the 200 mg ring (geometric means ratio [GMR], 2.36–3.97) and higher in the 100 mg ring at day 91 (GMR, 3.04). Dapivirine concentration in plasma and cervicovaginal fluid was consistently higher in the 200 mg and 100 mg compared with the 25 mg groups at all timepoints (visits at day 28, 56, and 91).
At study completion, the mean amount of residual dapivirine in the vaginal rings was ~21 mg in the 25 mg ring, 86.7 mg in the 100 mg ring, and 184.3 mg in the 200 mg ring. The estimated amount of dapivirine released over the 13-week period was a mean 11.2, 14.2, and 22.8 mg with the 25, 100, and 200 mg rings, respectively.
Eighty-two percent of the participants (n=40) reported full adherence over the 13 weeks of use, with no significant difference between groups. The reasons for ring removal were discomfort or minor genitourinary symptoms (n=3), menses or bleeding (n=1), for cleaning purposes (n=1), partner dislike of ring or not wanting partner to know of ring (n=2), and sexual intercourse or pelvic exam (n=2). There were two incidents of ring expulsion, one related to sexual intercourse and another due to tampon removal.
Most participants reported liking the vaginal rings, with a median score of 8 on the 10-point Likert scale, and reported being likely to use the ring if it was effective (median score of 9).
“Vaginal rings are a promising HIV prevention strategy that offer a fully woman-centred and reversible long-acting prevention approach,” noted Liu.
The monthly 25 mg dapivirine ring was shown to be effective and safe in two phase III trials. The extended duration versions could potentially reduce user burden and cost, streamline follow-up visits, and encourage adherence, he added.
“Future approval of extended duration rings, if shown effective, could provide more long-acting options and increase access and equity to HIV prevention in women,” concluded Liu.