Abstract
The HIV virus and hepatitis B virus nucleotide reverse transcriptase inhibitor tenofovir has been associated with proximal tubular toxicity; the latter was found to be predicted by plasma concentrations and with single-nucleotide polymorphisms in transporters-encoding genes. A cross-sectional analysis in adult HIV-positive patients with estimated creatinine clearance >60 ml min−1 was performed. Twelve-hour plasma and urinary tenofovir concentrations and single-nucleotide polymorphisms in several transporter-encoding genes were analysed. In 289 patients 12-h tenofovir plasma, urinary and urinary to plasma ratios were 69 ng ml−1 (interquartile range 51.5–95), 24.3 mg ml−1 (14.3–37.7) and 384 (209–560). At multivariate analysis estimated creatinine clearance, protease inhibitors co-administration and SLC28A2 CT/TT genotypes were independently associated with plasma tenofovir exposure; ABCC10 GA/AA genotypes and protease inhibitor co-administration were independently associated with the urinary to plasma tenofovir ratio. Tenofovir clearance was associated with genetic polymorphisms in host genes and with co-administered drugs: if confirmed by ongoing studies these data may inform treatment tailoring and/or dose reductions.
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Acknowledgements
This work was supported by a research grant from Gilead (Gilead Fellowship Program 2012, c2b35f7351).
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AC has received grants, travel grants and speaker’s honoraria from Abbvie, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Gilead Sciences, Viiv and Janssen-Cilag. SB has received grants, travel grants and consultancy fees from Abbvie, Boehringer-Inghelheim, BMS, Gilead Sciences, GlaxoSmithKline (GSK), MSD, Pfizer and Janssen-Cilag. GDP has received grants, travel grants and consultancy fees from Abbvie, Boehringer-Ingelheim, BMS, Gilead Sciences, GSK, MSD, Pfizer, Roche and Tibotec (Johnson & Johnson). The remaining authors declare no conflict of interest.
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Calcagno, A., Cusato, J., Marinaro, L. et al. Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines. Pharmacogenomics J 16, 514–518 (2016). https://doi.org/10.1038/tpj.2015.71
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DOI: https://doi.org/10.1038/tpj.2015.71
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