Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/ levonorgestrel vaginal rings
Date
2019Journal
PLoS ONEPublisher
Public Library of ScienceType
Article
Metadata
Show full item recordAbstract
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. Copyright 2019 Thurman et al.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066153443&doi=10.1371%2fjournal.pone.0217229&partnerID=40&md5=e90a5948fcae246bae1918b64a5853d8; http://hdl.handle.net/10713/10815ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0217229
Scopus Count
Collections
Related articles
- Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women.
- Authors: Thurman AR, Schwartz JL, Brache V, Clark MR, McCormick T, Chandra N, Marzinke MA, Stanczyk FZ, Dezzutti CS, Hillier SL, Herold BC, Fichorova R, Asin SN, Rollenhagen C, Weiner D, Kiser P, Doncel GF
- Issue date: 2018
- Differences in Local and Systemic TFV PK Among Premenopausal Versus Postmenopausal Women Exposed to TFV 1% Vaginal Gel.
- Authors: Thurman AR, Chandra N, Yousefieh N, Kimble T, Anderson SM, Cottrell M, Sykes C, Kashuba A, Schwartz JL, Doncel GF
- Issue date: 2018 May 1
- A phase 1 randomized placebo-controlled safety and pharmacokinetic trial of a tenofovir disoproxil fumarate vaginal ring.
- Authors: Keller MJ, Mesquita PM, Marzinke MA, Teller R, Espinoza L, Atrio JM, Lo Y, Frank B, Srinivasan S, Fredricks DN, Rabe L, Anderson PL, Hendrix CW, Kiser PF, Herold BC
- Issue date: 2016 Mar 13
- Safety and pharmacokinetics of single, dual, and triple antiretroviral drug formulations delivered by pod-intravaginal rings designed for HIV-1 prevention: A Phase I trial.
- Authors: Vincent KL, Moss JA, Marzinke MA, Hendrix CW, Anton PA, Pyles RB, Guthrie KM, Dawson L, Olive TJ, Butkyavichene I, Churchman SA, Cortez JM Jr, Fanter R, Gunawardana M, Miller CS, Yang F, Rosen RK, Vargas SE, Baum MM
- Issue date: 2018 Sep
- Safety and pharmacokinetics of intravaginal rings delivering tenofovir in pig-tailed macaques.
- Authors: Moss JA, Malone AM, Smith TJ, Butkyavichene I, Cortez C, Gilman J, Kennedy S, Kopin E, Nguyen C, Sinha P, Hendry RM, Guenthner P, Holder A, Martin A, McNicholl J, Mitchell J, Pau CP, Srinivasan P, Smith JM, Baum MM
- Issue date: 2012 Nov