Mitochondrial toxicity

Nucleoside analogue reverse transcriptase inhibitors (NRTI) were the first therapeutic agents to demonstrate clinical efficacy as antiretroviral therapy for HIV infection, and they continue to be used in contemporary highly active antiretroviral therapy (HAART) regimens that may combine three NRTIs, or two drugs from this class with either HIV protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs).

The use of NRTI therapy appears to be an important determinant of the durability and effectiveness of these HAART regimens, indicating that this drug class will be a component of HIV therapy for the foreseeable future. This knowledge also highlights the need for a comprehensive understanding of NRTI-induced drug toxicities.

As HIV infection becomes a “manageable” disease with greatly reduced morbidity and mortality attributable to immune deficiency, the identification, monitoring, and management of these adverse effects assumes proportionally greater importance in the clinical setting.