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Pharmacogenomics. 2019 Jan 10. doi: 10.2217/pgs-2018-0140. [Epub ahead of print]

Genetic variation of kinases and activation of nucleotide analog reverse transcriptase inhibitor tenofovir.

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Department of Medicine (Division of Clinical Pharmacology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.


As antiretroviral therapy has become more accessible across the world and coformulations have improved patient compliance; the morbidity and mortality of HIV/AIDS has decreased. However, there is still a substantial gap in knowledge regarding the impact of genetic variation on the metabolism of and response to some of the most commonly prescribed antiretrovirals, including the nucleotide reverse transcriptase inhibitor tenofovir. While it has been scientifically established that tenofovir must be activated to be efficacious against HIV, the enzymes responsible for this activation have not been well characterized. The purpose of this review is to summarize and clarify the scientific knowledge regarding the enzymes that phosphorylate and activate this clinically important drug.


HIV; antiretroviral therapy; drug metabolism; genetic variants; precision medicine


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