Trial reportAIDS (London, England)2016
A phase 1 randomized placebo-controlled safety and pharmacokinetic trial of a tenofovir disoproxil fumarate vaginal ring.
Trial report in AIDS (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02762617 (Phase 1 Safety and Pharmacokinetic Study of a Polyurethane Tenofovir Disoproxil Fumarate Vaginal Ring in Sexually Active Women), which is not on this map. Cited by 16 papers.
What it found
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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.
Phase 1 Safety and Pharmacokinetic Study of a Polyurethane Tenofovir Disoproxil Fumarate Vaginal Ring in Sexually Active Women (TDF IVR-002)
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- 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
- Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Preclinical Considerations for Long-acting Delivery of Tenofovir Alafenamide from Subdermal Implants for HIV Pre-exposure Prophylaxis.Pharmaceutical research · 2023Article
- Synthetic Mucin Gels with Self-Healing Properties Augment Lubricity and Inhibit HIV-1 and HSV-2 Transmission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Fundamental aspects of long-acting tenofovir alafenamide delivery from subdermal implants for HIV prophylaxis.Scientific reports · 2022Article
- Fused deposition modeling three-dimensional printing of flexible polyurethane intravaginal rings with controlled tunable release profiles for multiple active drugs.Drug delivery and translational research · 2022Article
- Reciprocal Modulation of Antiretroviral Drug and Steroid Receptor FunctionAntimicrobial agents and chemotherapy · 2019Article
- Phosphonate prodrugs: an overview and recent advances.Future medicinal chemistry · 2019Review
- Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection.PloS one · 2019Article
- 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.PLoS medicine · 2018Article
- Sustained Release Drug Delivery Applications of Polyurethanes.Pharmaceutics · 2018Review
- Article
- Pharmacokinetics of the Protein Microbicide 5P12-RANTES in Sheep following Single-Dose Vaginal Gel Administration.Antimicrobial agents and chemotherapy · 2017Article
- Attitudes and perceptions towards novel objective measures of ARV-based vaginal ring use: Results from a global stakeholder survey.PloS one · 2017Article
- Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes.Drug design, development and therapy · 2017Review
- Biomarkers and biometric measures of adherence to use of ARV-based vaginal rings.Journal of the International AIDS Society · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundTenofovir disoproxil fumarate (TDF), a prodrug of tenofovir (TFV), may be ideal for topical HIV preexposure prophylaxis because it has higher tissue and cell permeability than TFV; is not adversely impacted by seminal proteins; and its active metabolite, TFV-diphosphate (TFV-DP), has a long intracellular half-life. We engineered a TDF eluting polyurethane reservoir intravaginal ring (IVR) to provide near constant mucosal antiretroviral concentrations.
methodsA first-in-human randomized placebo-controlled trial was conducted to assess the safety and pharmacokinetics of the TDF IVR in healthy, sexually abstinent women (15 TDF and 15 placebo). Drug concentrations were measured in cervicovaginal fluid (CVF) obtained by swab, cervical tissue, plasma, and dried blood spots (DBS) over 14 days of continuous ring use.
resultsThere were 43 total, 23 reproductive tract, and eight product-related grade 1 adverse events. Steady-state CVF TFV concentrations were achieved proximal (vagina, ectocervix) and distal (introitus) to the TDF IVR 1 day after ring insertion. Median tissue TFV-DP concentrations 14 days after TDF IVR placement were 120 fmol/mg (interquartile range 90, 550). CVF collected from the cervix 1 week and 2 weeks after TDF IVR insertion provided significant protection against ex-vivo HIV challenge. Eleven of 14 (78%) participants had detectable TFV-DP DBS concentrations 14 days after TDF IVR placement, suggesting that DBS may provide a surrogate marker of adherence in future clinical trials.
conclusionA TDF IVR is safe, well tolerated, and results in mucosal TFV concentrations that exceed those associated with HIV protection. The findings support further clinical evaluation of this TDF IVR.
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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.