Trial reportPloS one2011
A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.
Trial report in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00594373 (Effect of Repeated Applications of Tenofovir Gel on Mucosal Mediators of Immunity and Intrinsic Antimicrobial Activity of Cervicovaginal Secretions in Women at Low Risk for HIV-1 Infection), which is not on this map. Cited by 58 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.
Effect of Repeated Applications of Tenofovir Gel on Mucosal Mediators of Immunity and Intrinsic Antimicrobial Activity of Cervicovaginal Secretions in Women at Low Risk for HIV-1 Infection
Who cites it
58 citing papers in PubMed, 82 citations in OpenAlex.
- Tenofovir Douche as HIV Preexposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics (DREAM 01).The Journal of infectious diseases · 2024Trial
- A phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir.Frontiers in cellular and infection microbiology · 2023Trial
- Trial
- 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
- Pharmacokinetics and Pharmacodynamics of Tenofovir Reduced-Glycerin 1% Gel in the Rectal and Vaginal Compartments in Women: A Cross-Compartmental Study With Directly Observed Dosing.Journal of acquired immune deficiency syndromes (1999) · 2018Trial
- Comparison of the Pharmacokinetics and Pharmacodynamics of Single-Dose Tenofovir Vaginal Film and Gel Formulation (FAME 05).Journal of acquired immune deficiency syndromes (1999) · 2018Trial
- Trial
- Trial
- Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods.Antimicrobial agents and chemotherapy · 2016Trial
- Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women.AIDS research and human retroviruses · 2016Trial
- Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066).AIDS research and human retroviruses · 2016Trial
- HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.Journal of acquired immune deficiency syndromes (1999) · 2014Trial
- Trial
- Trial
- RMP-02/MTN-006: A phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fumarate.AIDS research and human retroviruses · 2012Trial
- Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.Science translational medicine · 2012Trial
- Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.PloS one · 2012Trial
- Evaluating the impact of three progestin-based hormonal contraceptive methods on immunologic changes in the female genital tract and systemically (CHIME Study): a prospective cohort study protocol.BMC women's health · 2022Article
- Differences in Vaginal Microbiota, Host Transcriptome, and Proteins in Women With Bacterial Vaginosis Are Associated With Metronidazole Treatment Response.The Journal of infectious diseases · 2021Article
- Tenofovir and emtricitabine concentrations in hair are comparable between individuals on tenofovir disoproxil fumarate versus tenofovir alafenamide-based ART.Drug testing and analysis · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPreclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.
methods30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL) on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.
resultsA significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001) and fit a sigmoid E(max) pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.
conclusionsTenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development of models more predictive of microbicide efficacy.
trial registrationClinicalTrials.gov NCT00594373.
Indexed as
Identifiers
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.