Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/ levonorgestrel vaginal rings

Andrea Ries Thurman, Jill L. Schwartz, Jacques Ravel, Pawel Gajer, Mark A Marzinke, Nazita Yousefieh, Sharon M. Anderson, Gustavo F. Doncel

Research output: Contribution to journalArticle

Abstract

Recent data support that the vaginal microbiota may alter mucosal pharmacokinetics (PK) of topically delivered microbicides. Our team developed an intravaginal ring (IVR) that delivers tenofovir (TFV) (8-10 mg/day) alone or with levonorgestrel (LNG) (20 ug/day). We evaluated the effect of IVRs on the vaginal microbiota, and describe how the vaginal microbiota impacts mucosal PK of TFV. CONRAD A13-128 was a randomized, placebo controlled phase I study. We randomized 51 women to TFV, TFV/LNG or placebo IVR. We assessed the vaginal microbiota by sequencing the V3-V4 regions of 16S rRNA genes prior to IVR insertion and after approximately 15 days of use. We measured the concentration of TFV in the cervicovaginal (CV) aspirate, and TFV and TFV-diphosphate (TFV-DP) in vaginal tissue at the end of IVR use. The change in relative or absolute abundance of vaginal bacterial phylotypes was similar among active and placebo IVR users (all q values >0.13). TFV concentrations in CV aspirate and vaginal tissue, and TFV-DP concentrations in vaginal tissue were not significantly different among users with community state type (CST) 4 versus those with Lactobacillus dominated microbiota (all p values >0.07). The proportions of participants with CV aspirate concentrations of TFV >200,000 ng/mL and those with tissue TFV-DP concentrations >1,000 fmol/mg were similar among women with anaerobe versus Lactobacillus dominated microbiota (p = 0.43, 0.95 respectively). There were no significant correlations between the CV aspirate concentration of TFV and the relative abundances of Gardnerella vaginalis or Prevotella species. Tissue concentrations of TFV-DP did not correlate with any the relative abundances of any species, including Gardnerella vaginalis. In conclusion, active IVRs did not differ from the placebo IVR on the effect on the vaginal microbiota. Local TFV and TFV-DP concentrations were high and similar among IVR users with Lactobacillus dominated microbiota versus CST IV vaginal microbiota.

Original languageEnglish (US)
Article numbere0217229
JournalPloS one
Volume14
Issue number5
DOIs
StatePublished - May 1 2019

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Tenofovir
Female Contraceptive Devices
Levonorgestrel
Pharmacokinetics
Microbiota
pharmacokinetics
placebos
Gardnerella vaginalis
Lactobacillus
Tissue
Placebos
Prevotella
microbiome
anaerobes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/ levonorgestrel vaginal rings. / Thurman, Andrea Ries; Schwartz, Jill L.; Ravel, Jacques; Gajer, Pawel; Marzinke, Mark A; Yousefieh, Nazita; Anderson, Sharon M.; Doncel, Gustavo F.

In: PloS one, Vol. 14, No. 5, e0217229, 01.05.2019.

Research output: Contribution to journalArticle

Thurman, Andrea Ries ; Schwartz, Jill L. ; Ravel, Jacques ; Gajer, Pawel ; Marzinke, Mark A ; Yousefieh, Nazita ; Anderson, Sharon M. ; Doncel, Gustavo F. / Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/ levonorgestrel vaginal rings. In: PloS one. 2019 ; Vol. 14, No. 5.
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AU - Gajer, Pawel

AU - Marzinke, Mark A

AU - Yousefieh, Nazita

AU - Anderson, Sharon M.

AU - Doncel, Gustavo F.

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