Pharmacokinetics of Dapivirine Transfer into Blood Plasma, Breast Milk, and Cervicovaginal Fluid of Lactating Women using the Dapivirine Vaginal Ring [Antiviral Agents]

Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but are rarely included in trials. The 25 mg dapivirine vaginal ring (VR) reduced women's risk of sexually transmitted HIV infection in two Phase 3 trials conducted in Africa. MTN-029/IPM 039 was a Phase 1, open-label study of dapivirine VR use among lactating women. MTN-029/IPM 039 enrolled 16 healthy adult women who had already weaned their infants but were still able to express breast milk. Women were instructed to use the VR continuously for 14 days and provided milk, plasma, and cervicovaginal fluid (CVF) samples for pharmacological analysis. No infants were exposed to drug, but infant dosage was estimated per FDA guidance. Adverse events (AEs) were collected at all contacts. The study was completed with 100% participant retention. Median dapivirine concentrations were 676 pg/mL in breast milk, 327 pg/mL in plasma (milk:plasma ratio ~2.0), and 36.25 ng/mg in CVF. Six participants experienced ten total AEs, none of which required VR discontinuation. The estimated mean daily infant dosage was 74.3 ng/kg/day. In this first study of dapivirine exposure during lactation, dapivirine VR use was associated with lower concentrations of detectable dapivirine in milk and plasma compared to CVF, and a favorable safety profile. Estimated daily levels of infant dapivirine exposure were also low. Additional studies are needed to evaluate longer periods of dapivirine VR use among BF mother-infant pairs living in regions with higher incidence of sexually transmitted HIV infection.

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