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Updated: Nov 5, 2025

Prediction of HIV-1 Coreceptor Usage Tropism by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid
Eric H Decloedt1,2, Phumla Z Sinxadi2, Lubbe Wiesner2
1Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
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.
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