Pharmacokinetics of dapivirine transfer into blood plasma, breast milk, and cervicovaginal fluid of lactating women using the dapivirine vaginal ring

Lisa M. Noguchi, Craig Hoesley, Cliff Kelly, Rachel Scheckter, Katherine Bunge, Annalene Nel, Mark A Marzinke, Craig Hendrix, Charlene S. Dezzutti, Sharon L. Hillier, Debra L. Bogen, Jeanna M. Piper, Richard H. Beigi

Research output: Contribution to journalArticle

Abstract

Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but they 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. We conducted a phase 1, open-label study (MTN-029/IPM 039) of dapivirine VR use among lactating women in Pittsburgh, PA, and Birmingham, AL, USA. 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 the drug, but infant dosage was estimated according to 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 10 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 than in CVF samples 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. (This study has been registered at ClinicalTrials.gov under registration no. NCT02808949.)

Original languageEnglish (US)
Article numbere01930-18
JournalAntimicrobial agents and chemotherapy
DOIs
StatePublished - Mar 1 2019

Fingerprint

Female Contraceptive Devices
Human Milk
Pharmacokinetics
Milk
Sexually Transmitted Diseases
Breast Feeding
HIV Infections
TMC120-R147681
Lactation
Mothers
HIV
Pharmacology
Safety

Keywords

  • Breastfeeding
  • Dapivirine
  • HIV
  • Lactation
  • Pharmacokinetics
  • Vaginal

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Pharmacokinetics of dapivirine transfer into blood plasma, breast milk, and cervicovaginal fluid of lactating women using the dapivirine vaginal ring. / Noguchi, Lisa M.; Hoesley, Craig; Kelly, Cliff; Scheckter, Rachel; Bunge, Katherine; Nel, Annalene; Marzinke, Mark A; Hendrix, Craig; Dezzutti, Charlene S.; Hillier, Sharon L.; Bogen, Debra L.; Piper, Jeanna M.; Beigi, Richard H.

In: Antimicrobial agents and chemotherapy, 01.03.2019.

Research output: Contribution to journalArticle

Noguchi, Lisa M. ; Hoesley, Craig ; Kelly, Cliff ; Scheckter, Rachel ; Bunge, Katherine ; Nel, Annalene ; Marzinke, Mark A ; Hendrix, Craig ; Dezzutti, Charlene S. ; Hillier, Sharon L. ; Bogen, Debra L. ; Piper, Jeanna M. ; Beigi, Richard H. / Pharmacokinetics of dapivirine transfer into blood plasma, breast milk, and cervicovaginal fluid of lactating women using the dapivirine vaginal ring. In: Antimicrobial agents and chemotherapy. 2019.
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abstract = "Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but they 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. We conducted a phase 1, open-label study (MTN-029/IPM 039) of dapivirine VR use among lactating women in Pittsburgh, PA, and Birmingham, AL, USA. 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 the drug, but infant dosage was estimated according to 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 10 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 than in CVF samples 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. (This study has been registered at ClinicalTrials.gov under registration no. NCT02808949.)",
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