Phosphorylation of nucleoside analog antiretrovirals: A review for clinicians

Nucleoside analogs (zidovudine, didanosine, zalcitabine, stavudine, abacavi r, lamivudine) have been administered as antiretroviral agents for more tha n a decade. They undergo anabolic phosphorylation by intracellular kinases to form triphosphates, which inhibit human immunodeficiency virus replicati on by competitively inhibiting viral reverse transcriptase. Numerous method s are used to elucidate the intracellular metabolic pathways of these agent s. Intracellular and extracellular factors affect intracellular phosphoryla tion. Lack of standardization and complexity of methods used to study phosp horylation in patients limit interpretation of study results and comparabil ity of findings across studies. However, in vitro and in vivo studies give important insights into mechanisms of action, metabolic feedback mechanisms , antiviral effects, and mechanisms of toxicity, and have influenced dosing regimens of nucleoside analogs.