Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid

Southern African Journal of HIV Medicine

Field Value
Title Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid
Creator Decloedt, Eric H. Sinxadi, Phumla Z. Wiesner, Lubbe Joska, John A. Haas, David W. Maartens, Gary
Subject Pharmacokinetics; Pharmacogenetics pharmacokinetics; pharmacogenetics; tenofovir; emtricitabine; cerebrospinal fluid
Description Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration.Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine.Method: We collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold.Results: The geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing.Conclusion: No genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine.
Publisher AOSIS
Contributor This work was supported by the South African Medical Research Council and the European and Developing Countries Clinical Trials Partnership (SP.2011.41304.065). The drug assays analysed at the University of Cape Town were supported in part by the National
Date 2021-04-28
Type info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion — —
Format text/html application/epub+zip text/xml application/pdf
Identifier 10.4102/sajhivmed.v22i1.1206
Source Southern African Journal of HIV Medicine; Vol 22, No 1 (2021); 24 pages 2078-6751 1608-9693
Language eng
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Rights Copyright (c) 2021 Eric H. Decloedt, Phumla Z. Sinxadi, Lubbe Wiesner, John A. Joska, David W. Haas, Gary Maartens