From old to new nucleoside reverse transcriptase inhibitors: changes in body fat composition, metabolic parameters and mitochondrial toxicity after the switch from thymidine analogs to tenofovir or abacavir.

INTRODUCTION: Thymidine analogs zidovudine (AZT) and stavudine (d4T) have been widely used because of their antiviral activity against HIV, but at the expense of high toxicity, mainly related to mitochondrial damage. Many studies have been performed replacing AZT or d4T with newer nucleoside analogs reverse transcriptase inhibitors (NRTIs) with less toxicity, such as tenofovir (TDF) or abacavir (ABC), maintaining virological efficacy.

AREAS COVERED: Relevant literature was identified using a PubMed search of articles published up to June 2010. Search terms included: 'thymidine analogs', 'stavudine', 'zidovudine', 'd4T', 'AZT', 'ZDV', 'treatment switch'. Original articles in which d4T or AZT had been replaced by TDF or ABC as switch strategies (with undetectable viral load) were reviewed where information about body fat distribution, mitochondrial functionality and/or plasma lipid parameters were available. Relevant references from these articles were also considered. Only studies performed in adult patients (18 years or older) are included. The readers will gain a better understanding of the toxicity caused by thymidine analogs, the treatment alternatives and the benefits observed after treatment switch to newer NRTIs.

EXPERT OPINION: Thymidine analogs AZT and d4T yield considerable toxicity and proactive switch to newer NRTIs such as TDF or ABC is necessary in order to avoid or partially reverse such side effects.