An intravaginal ring for HIV pre-exposure prophylaxis: assessment of safety and pharmacokinetics in a randomized, placebo-controlled clinical trial.
9 affiliations
- 1Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, United States.
- 2Department of Chemistry, Oak Crest Institute of Science, Monrovia, CA, United States.
- 3Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, MD, United States.
- 4Department of Pathology, Johns Hopkins University, Baltimore, MD, United States.
- 5Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, United States.
- 6Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States.
- 7Jumpstart Research Consulting, LLC, Santa Fe, NM, United States.
- 8Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
- 9Kelly Government Solutions, Contractor to Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
Abstract
Introduction
In Eastern and Southern Africa, 63% of new HIV infections occurred in women and girls, with adolescent girls and young women representing a particularly vulnerable subpopulation. Effective vaginal products for HIV prevention are desirable because they are underrepresented in the currently approved portfolio and have attributes motivating product use. In this trial, we evaluated an innovative intravaginal ring (pod-IVR) as a platform for HIV pre-exposure prophylaxis (PrEP).Objective
To measure the safety and multicompartment pharmacokinetics (PKs) of a pod-IVR delivering tenofovir disoproxil fumarate (TDF) combined with emtricitabine (FTC) in healthy women over 28 days.Methods
The Phase 1 clinical trial consisted of a randomized order, controlled, double-blinded, crossover design. Ten women received either an active TDF-FTC pod-IVR or a placebo pod-IVR for 28 days, determined by 1:1 randomization, followed by product crossover for another 28 days. Safety was assessed in terms of adverse events related to product use, colposcopic examination, cervicovaginal epithelium thickness measurement by optical coherence tomography, and culture-independent assessment of the vaginal microbiome. Drug and/or drug metabolite concentrations were measured in cervicovaginal fluid (CVF), vaginal tissue, rectal tissue, rectal fluid, and plasma.Results
There was no evidence of a statistically significant difference in related adverse-event counts between study products. There also was no evidence suggesting the study product altered the vaginal microbiome systematically or reproducibly. Systemic plasma exposure to tenofovir (TFV) and FTC was low, consistent with topical delivery. High median CVF concentrations of TFV (38.9 ng mg⁻¹; 135×10³ fmol mg⁻¹) and FTC (239 ng mg⁻¹; 966×10³ fmol mg⁻¹) were measured. Median vaginal tissue concentrations of the anabolites responsible for inhibition of HIV reverse transcriptase exceeded our target concentrations: TFV diphosphate 0.651×10³ fmol mg⁻¹ and FTC triphosphate 0.180×10³ fmol mg⁻¹. Drug concentrations in rectal tissue samples generally were below the analytical lower limits of quantification, but were quantifiable in rectal fluids, 130 (TFV) and 300 (FTC) times lower than in CVF.Conclusions
The TDF-FTC pod-IVRs were safe and well-tolerated over the 28 days of consecutive use. The PK data met the target benchmarks associated with protection from vaginal HIV infection.Clinical trial registration
https://clinicaltrials.gov/study/NCT03255915, identifier NCT03255915.
Related
- Single-dose/day versus extended antibiotic prophylaxis for elective urological surgery: a prospective randomized controlled trial
- Pharmacokinetics of injectable favipiravir: phase I, randomized, double-blind, placebo-controlled study in healthy East Asian subjects
- A Phase I, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of intravenous ertapenem and zidebactam in combination (WCK 6777) in healthy adult subjects
- Higher tissue concentrations of cefuroxime achieved with preoperative stand-alone intraosseous regional prophylaxis in robotic-assisted total knee arthroplasty: a randomized controlled trial.
- Population pharmacokinetics of cefazolin administered as prophylaxis in paediatric patients undergoing cardiac surgery
BibTeX
@article{vincent2026intravaginal,
title = {{An intravaginal ring for HIV pre-exposure prophylaxis: assessment of safety and pharmacokinetics in a randomized, placebo-controlled clinical trial.}},
author = {Kathleen L Vincent and John A Moss and Mark A Marzinke and Richard B Pyles and Lauren Dawson and Trevelyn J Olive and Irina Butkyavichene and Amalia E Castonguay and John M Cortez and Mariana Remedios-Chan and Patricia Galvan and Sofia Rivera and Simon Webster and Manjula Gunawardana and Amy P Adler and Christina M Ramirez and Hans M L Spiegel and Craig W Hendrix and Peter A Anton and Marc M Baum},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1955105},
url = {https://europepmc.org/article/MED/42903070},
note = {CC BY},
}
RIS
TY - JOUR
TI - An intravaginal ring for HIV pre-exposure prophylaxis: assessment of safety and pharmacokinetics in a randomized, placebo-controlled clinical trial.
AU - Kathleen L Vincent
AU - John A Moss
AU - Mark A Marzinke
AU - Richard B Pyles
AU - Lauren Dawson
AU - Trevelyn J Olive
AU - Irina Butkyavichene
AU - Amalia E Castonguay
AU - John M Cortez
AU - Mariana Remedios-Chan
AU - Patricia Galvan
AU - Sofia Rivera
AU - Simon Webster
AU - Manjula Gunawardana
AU - Amy P Adler
AU - Christina M Ramirez
AU - Hans M L Spiegel
AU - Craig W Hendrix
AU - Peter A Anton
AU - Marc M Baum
PY - 2026
DA - 2026/10/06
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1955105
UR - https://europepmc.org/article/MED/42903070
AB - Introduction In Eastern and Southern Africa, 63% of new HIV infections occurred in women and girls, with adolescent girls and young women representing a particularly vulnerable subpopulation. Effective vaginal products for HIV prevention are desirable because they are underrepresented in the currently approved portfolio and have attributes motivating product use. In this trial, we evaluated an innovative intravaginal ring (pod-IVR) as a platform for HIV pre-exposure prophylaxis (PrEP).Objective To measure the safety and multicompartment pharmacokinetics (PKs) of a pod-IVR delivering tenofovir disoproxil fumarate (TDF) combined with emtricitabine (FTC) in healthy women over 28 days.Methods The Phase 1 clinical trial consisted of a randomized order, controlled, double-blinded, crossover design. Ten women received either an active TDF-FTC pod-IVR or a placebo pod-IVR for 28 days, determined by 1:1 randomization, followed by product crossover for another 28 days. Safety was assessed in terms of adverse events related to product use, colposcopic examination, cervicovaginal epithelium thickness measurement by optical coherence tomography, and culture-independent assessment of the vaginal microbiome. Drug and/or drug metabolite concentrations were measured in cervicovaginal fluid (CVF), vaginal tissue, rectal tissue, rectal fluid, and plasma.Results There was no evidence of a statistically significant difference in related adverse-event counts between study products. There also was no evidence suggesting the study product altered the vaginal microbiome systematically or reproducibly. Systemic plasma exposure to tenofovir (TFV) and FTC was low, consistent with topical delivery. High median CVF concentrations of TFV (38.9 ng mg⁻¹; 135×10³ fmol mg⁻¹) and FTC (239 ng mg⁻¹; 966×10³ fmol mg⁻¹) were measured. Median vaginal tissue concentrations of the anabolites responsible for inhibition of HIV reverse transcriptase exceeded our target concentrations: TFV diphosphate 0.651×10³ fmol mg⁻¹ and FTC triphosphate 0.180×10³ fmol mg⁻¹. Drug concentrations in rectal tissue samples generally were below the analytical lower limits of quantification, but were quantifiable in rectal fluids, 130 (TFV) and 300 (FTC) times lower than in CVF.Conclusions The TDF-FTC pod-IVRs were safe and well-tolerated over the 28 days of consecutive use. The PK data met the target benchmarks associated with protection from vaginal HIV infection.Clinical trial registration https://clinicaltrials.gov/study/NCT03255915, identifier NCT03255915.
SN - 2235-2988
ER -