ArticleAntimicrobial agents and chemotherapy2014
Correlation between plasma, intracellular, and cervical tissue levels of raltegravir at steady-state dosing in healthy women.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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.
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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.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- The Effect of Rifampicin on Darunavir, Ritonavir, and Dolutegravir Exposure within Peripheral Blood Mononuclear Cells: a Dose Escalation Study.Antimicrobial agents and chemotherapy · 2022Article
- Long-Term Suppressive cART Is Not Sufficient to Restore Intestinal Permeability and Gut Microbiota Compositional Changes.Frontiers in immunology · 2021Article
- Validation of a UHPLC-MS/MS Method to Quantify Twelve Antiretroviral Drugs within Peripheral Blood Mononuclear Cells from People Living with HIV.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Variable cellular ivacaftor concentrations in people with cystic fibrosis on modulator therapy.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Article
- Pharmacology of Antiretrovirals in the Female Genital Tract for HIV Prevention.Journal of clinical pharmacology · 2018Review
- 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
- Susceptibility of porcine endogenous retrovirus to anti-retroviral inhibitors.Xenotransplantation · 2016Article
- Relationship Between Genital Drug Concentrations and Cervical Cellular Immune Activation and Reconstitution in HIV-1-Infected Women on a Raltegravir Versus a Boosted Atazanavir Regimen.AIDS research and human retroviruses · 2015Observational
- Pharmacokinetics of antiretrovirals in mucosal tissue.Expert opinion on drug metabolism & toxicology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Raltegravir is an antiretroviral with potential value for preexposure prophylaxis (PrEP) against HIV, but the intracellular pharmacokinetics in genital tissue have not been described. In this study, healthy, HIV-uninfected nonpregnant women took 400 mg of raltegravir twice daily for 22 days. On day 8, 15, and 22, blood was collected 0, 4, 6, 8, and 12 h and cervical biopsy specimens taken 0, 6, and 12 h after raltegravir dosing. Plasma and intracellular raltegravir concentrations in peripheral blood mononuclear cells (PBMC) and cervical tissue were measured by tandem mass spectrometry. Linear mixed effects models evaluated correlations between different sample types, as well as differences in concentration between phases of the menstrual cycle. Ten women were enrolled: 9 completed all three visits and 1 completed two visits. The age (mean ± standard deviation) of participants was 30 ± 8 years. Trough plasma concentrations of raltegravir 12 h after a directly observed dose were above the HIV 95% inhibitory concentration (IC95) of 33 nM (14.6 ng/ml) in 96% of measurements, compared to 67% of PBMC and 89% of cervical tissue trough values. Across all measurements, only 2% (3/135) of plasma values fell below the IC95, compared to 10% (13/135) for PBMC and 6% (5/81) for cervical tissue. There was no impact of menstrual phase on raltegravir concentrations. In conclusion, cervical tissue raltegravir concentrations were no greater than plasma concentrations, and ∼10% of all cervical tissue trough values were below the IC95, making the current twice-daily formulation of raltegravir impractical for PrEP.
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Registered trials
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