ArticleJournal of acquired immune deficiency syndromes (1999)2016
Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design.
Article in Journal of acquired immune deficiency syndromes (1999), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02983110 (Does Sex Hormone Therapy Decrease Nucleos), which is not on this map. Cited by 14 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.
Does Sex Hormone Therapy Decrease Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Active Metabolite Formation in Mucosal Tissues?
Who cites it
14 citing papers in PubMed.
- Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK-2048A Intravaginal Rings.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with men.Journal of the International AIDS Society · 2018Trial
- Levels of Intracellular Phosphorylated Tenofovir and Emtricitabine Correlate With Natural Substrate Concentrations in Peripheral Blood Mononuclear Cells of Persons Prescribed Daily Oral Truvada for HIV Pre-exposure Prophylaxis.Journal of acquired immune deficiency syndromes (1999) · 2017Trial
- Heterogeneous Antiretroviral Drug Exposure in Male and Female Genital Tract Tissues.The Journal of infectious diseases · 2025Article
- Antiretroviral drug exposure in urethral and glans surface sampling of the penis.The Journal of antimicrobial chemotherapy · 2021Article
- Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021Review
- Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry.Wellcome open research · 2021Article
- Perspectives on the utility and interest in a point-of-care urine tenofovir test for adherence to HIV pre-exposure prophylaxis and antiretroviral therapy: an exploratory qualitative assessment among U.S. clients and providers.AIDS research and therapy · 2020Article
- Does Mucosal B1 Activation Result in the Accumulation of Peak IgM During Chronic Intrarectal SIVmac239 Exposure to Protect Chinese-Origin Rhesus Macaques From Disease Progression?Frontiers in microbiology · 2020Article
- Pharmacology of Antiretrovirals in the Female Genital Tract for HIV Prevention.Journal of clinical pharmacology · 2018Review
- Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children.Journal of clinical pharmacology · 2018Review
- Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum.Journal of acquired immune deficiency syndromes (1999) · 2018Article
- Differences in Local and Systemic TFV PK Among Premenopausal Versus Postmenopausal Women Exposed to TFV 1% Vaginal Gel.Journal of acquired immune deficiency syndromes (1999) · 2018Article
- Importance of Drug Pharmacokinetics at the Site of Action.Clinical and translational science · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
backgroundQuantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration (cervicovaginal fluid; CVF) or swab (rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized.
methodsForty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50%-200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48 hours. Relationships between these paired samples were characterized by linear and multiple linear regression. Adjusted r values were used to select the final predictive models.
resultsCVF exposure increased linearly with dose for all antiretrovirals (r(2) ≥ 0.23, P ≤ 0.02) except raltegravir (r(2) = 0.08, P = 0.19). In RF, only emtricitabine increased linearly with dose (r(2) = 0.27, P = 0.01). For all antiretrovirals, CVF and RF concentrations significantly correlated with mucosal tissue concentrations (female genital tract r(2) ≥ 0.37, rectal tissue (2)r ≥ 0.50, P ≤ 0.001). In the final multivariate models, plasma and fluid concentrations were both associated with FGT concentrations for all antiretrovirals (r(2) ≥ 0.81, P < 0.001). The same was noted for rectal tissue (r(2) ≥ 0.58, P < 0.001) except for tenofovir, for which RF alone was predictive of tissue concentration (r(2) = 0.91, P < 0.001).
conclusionsMucosal fluids were positively correlated with tissue concentrations and including plasma concentrations improved the regression models in most cases. Dose linearity in CVF, but not RF, suggests a saturation process in lower gastrointestinal tract tissue. These findings suggest that mucosal fluid and plasma concentrations may be used for qualitative inference of tissue concentrations for these antiretrovirals.
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