Pharmacokinetics, safety, and vaginal bleeding associated with continuous versus cyclic 90-day use of dapivirine and levonorgestrel vaginal rings for multipurpose prevention of HIV and pregnancy.

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Publisher: John Wiley & Sons, Inc.
Document Type: Report; Author abstract
Length: 441 words
Lexile Measure: 210L

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Abstract :

Background: We compared pharmacokinetics, safety, and vaginal bleeding associated with continuous versus cyclic use of a 90-day multipurpose prevention technology (MPT) vaginal ring for sustained delivery of dapivirine (DPV) for HIV pre-exposure prophylaxis and levonorgestrel (LNG) for contraception. Methods: In this Phase-1 trial, healthy HIV-uninfected women were randomized (1:1) to continuous or cyclic (28-days in/2-days out) use pattern of an MPT ring containing 200 mg DPV/320 mg LNG over 90-days. We quantified plasma DPV and LNG via liquid chromatography-mass spectrometry. We assessed vaginal bleeding and adverse events (AE) by daily text messaging. Results: Twenty-five evaluable participants had median age 36.0 years (range 21 to 43) and BMI 27 (range 20 to 39), and 20 (80%) self-identified as white. There were 84 AEs: 59 Grade-1, 24 Grade-2, and one Grade-4 (anemia related to cyclic product use). The number of women with = Grade-2 genitourinary AEs did not differ by continuous (3/12, 25%) or cyclic (5/13, 38%) use. With continuous use, median Cmax for DPV and LNG were 750 pg/mL (IQR 475 to 1401) and 1675 pg/mL (IQR 645 to 2575), respectively (Figure 1). Two days after ring removal (cyclic group), plasma DPV remained = concentration associated with previously demonstrated efficacy. Number of days with no bleeding, spotting/light, moderate, and heavy bleeding did not differ by use pattern (Table 1). Conclusions: Serum DPV and LNG concentrations previously associated with efficacy for HIV and pregnancy prevention respectively are achieved or exceeded with cyclic and continuous use of this MPT ring without toxicity. Vaginal bleeding profiles did not differ.

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Gale Document Number: GALE|A656303516