The Cellular Pharmacology of Nucleoside‐ and Nucleotide‐Analogue Reverse‐Transcriptase Inhibitors and Its Relationship to Clinical Toxicities

Citations Over TimeTop 10% of 2004 papers

Abstract

Nucleoside- and nucleotide-analogue reverse-transcriptase inhibitors (NRTIs) require intracellular phosphorylation for anti-human immunodeficiency virus (HIV) activity and toxicity. Long-term toxicities associated with NRTIs may be related to overactivation of this process. In vitro experiments have shown increased rates of NRTI and endogenous nucleoside phosphorylation to be associated with cellular activation. Patients with advanced HIV disease often have overexpression of cytokines, which corresponds to an elevated cellular activation state. These patients also have higher rates of NRTI phosphorylation and NRTI toxicity, suggesting an interaction between a proinflammatory biological state, NRTI phosphorylation, and toxicity. Studies suggest that women may have higher rates of NRTI phosphorylation than do men, as well as increased risk for NRTI-induced toxicity. Future research is needed to understand the NRTI activation process and improve the long-term toxicity profile of NRTIs. Such research should include comparisons of NRTI phosphorylation according to sex and cellular activation state (i.e., elevated vs. low).

Related Papers

• → Antiviral Drug Resistance and the Need for Development of New HIV-1 Reverse Transcriptase Inhibitors(2012)104 cited
• → A Short-Term Clinical Evaluation of L-697,661, a Non-Nucleoside Inhibitor of HIV-1 Reverse Transcriptase(1993)147 cited
• → A Review of Recent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Research Activity(2002)23 cited
• → Identification of reverse transcriptase mutations associated with HIV-1 drug resistance mainly against non-nucleoside reverse transcriptase inhibitors in treatment-naive patients(1999)9 cited
• → Comparison of the Dynamics of Resistance-Associated Mutations to Nucleoside Reverse Transcriptase Inhibitors, Nonnucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors after Cessation of Antiretroviral Combination Therapy(2004)16 cited