ArticleJCI insight2018
Vaginal microbiome modulates topical antiretroviral drug pharmacokinetics.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Trial
- Phase 1 randomized pharmacokinetic and safety study of a 90-day tenofovir vaginal ring in the United States.Journal of the International AIDS Society · 2024Trial
- Vaginal Microbiota and Mucosal Pharmacokinetics of Tenofovir in Healthy Women Using a 90-Day Tenofovir/Levonorgestrel Vaginal Ring.Frontiers in cellular and infection microbiology · 2022Trial
- Tenofovir disoproxil fumarate intravaginal ring for HIV pre-exposure prophylaxis in sexually active women: a phase 1, single-blind, randomised, controlled trial.The lancet. HIV · 2019Trial
- Evaluating Vaginal Microbiome Effects on Antiretroviral Exposure in the Female Genital Tract Using Pharmacometric and Machine Learning Approaches.Clinical pharmacology and therapeutics · 2026Article
- Sustained mucosal delivery of SAMT-247 via an intravaginal ring reduces the risk of SIVCell reports. Medicine · 2026Article
- A cell-impermeable kinase inhibitor uncovers outside-in signaling pathways that promote HIV-1 infection.Journal of virology · 2026Article
- Prevotella bivia Influences Antiretroviral Pharmacokinetics and Viral Replication in an Ex Vivo Vaginal Tissue Model.Clinical and translational science · 2026Article
- Genomic Diversity of VaginalViruses · 2026Article
- The female microbiome in HIV prevention, pathogenesis, and treatment.Current opinion in HIV and AIDS · 2026Review
- Glypican-1 upregulation elicited in response to a cell-impermeable kinase inhibitor and its overexpression enhance HIV-1 infection.bioRxiv : the preprint server for biology · 2025Article
- Vaginal pharmacomicrobiomics modulates risk of persistent and recurrent bacterial vaginosis.NPJ biofilms and microbiomes · 2025Review
- No change in key HIV target cell markers following initiation of three progestin-based hormonal contraception methods: findings from the CHIME study.Frontiers in immunology · 2025Article
- Female Genital Tract Host Factors and Tenofovir and Lamivudine Active Metabolites.The Journal of infectious diseases · 2024Article
- The Application of Nano Drug Delivery Systems in Female Upper Genital Tract Disorders.Pharmaceutics · 2024Review
- Article
- Formulation and characterization of pressure-assisted microsyringe 3D-printed scaffolds for controlled intravaginal antibiotic release.International journal of pharmaceutics · 2023Article
- Interactions between microbiota and cervical epithelial, immune, and mucus barrier.Frontiers in cellular and infection microbiology · 2023Review
- Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2022Review
- Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Tenofovir gel and dapivirine ring provided variable HIV protection in clinical trials, reflecting poor adherence and possibly biological factors. We hypothesized that vaginal microbiota modulates pharmacokinetics and tested the effects of pH, individual bacteria, and vaginal swabs from women on pharmacokinetics and antiviral activity. Tenofovir, but not dapivirine, uptake by human cells was reduced as pH increased. Lactobacillus crispatus actively transported tenofovir leading to a loss in drug bioavailability and culture supernatants from Gardnerella vaginalis, but not Atopobium vaginae, blocked tenofovir endocytosis. The inhibition of endocytosis mapped to adenine. Adenine increased from 65.5 μM in broth to 246 μM in Gardnerella, but decreased to 9.5 μM in Atopobium supernatants. This translated into a decrease in anti-HIV activity when Gardnerella supernatants or adenine were added to cultures. Dapivirine was also impacted by microbiota, as drug bound irreversibly to bacteria, resulting in decreased antiviral activity. When drugs were incubated with vaginal swabs, 30.7% ± 5.7% of dapivirine and 63.9% ± 8.8% of tenofovir were recovered in supernatants after centrifugation of the bacterial cell pellet. In contrast, no impact of microbiota on the pharmacokinetics of the prodrugs, tenofovir disoproxil fumarate or tenofovir alafenamide, was observed. Together, these results demonstrate that microbiota may impact pharmacokinetics and contribute to inconsistent efficacy.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.