title: Practical Considerations For Developing Nucleoside Reverse Transcriptase Inhibitors.
abstract: Nucleoside reverse transcriptase inhibitors (NRTI) remain a cornerstone of current antiretroviral regimens in combinations usually with a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase inhibitor (INI). The antiretroviral efficacy and relative safety of current NRTI results from a tight and relatively specific binding of their phosphorylated nucleoside triphosphates (NRTI-TP) with the HIV-1 reverse transcriptase which is essential for replication. The intracellular stability of NRTI-TP produces a sustained antiviral response, which makes convenient dosing feasible. Lessons learned regarding NRTI pharmacology screening, development, and use are discussed. NRTI and prodrugs currently under clinical development are outlined.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA ; Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
authors.forename: Selwyn J
authors.initials: SJ
authors.lastname: Hurwitz
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
keywords: HIV; antiviral agents; nucleoside analogs; pharmacology
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