Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway.

After zidovudine (ZDV), a 3′-azido analogue of thymidine, was found to be an effective antiretroviral drug against HIV [1,2], other nucleoside analogues inhibiting reverse transcriptase (RT) soon followed: didanosine (ddI), zalcitabine (ddC), lamivudine (3TC), stavudine (D4T), and recently abacavir (1592U89) [3–7]. These drugs have demonstrated efficacy in reduction of morbidity and mortality, especially in combination therapy [8–10]. A special feature of some of these drugs is the protection against AIDS dementia complex, which appears to be related to good penetration of the blood–brain barrier [11–13]. Although the introduction of protease inhibitors has changed the management of HIV infection drastically, this cerebroprotective property will assert the role of these nucleoside RT inhibitors (NRTI) as a cornerstone of antiretroviral therapy [9,10].