[Use of thymidine-sparing regimens in first-line therapy and in switches from thymidine analogues]

Therapy with two NRTIs/NtRTI represents the current basis of highly active antiretroviral therapy (HAART) and is almost always associated either with a NNRTI or a protease inhibitor. Thymidine analogues zidovudine and stavudine were largely used in the past and the use of backbones not including one of them was uncommon. However, the use of thymidine analogues today has several drawbacks, such as fragile pharmacokinetics, the need of two daily doses, unsatisfactory safety and toxicity profiles, a large number of pills and important cross-resistance phenomena. The possibility of using backbones not including thymidine analogues is thus becoming increasingly popular, provided that efficacy is not affected. Moreover, as some of the problems related to thymidine analogue toxicity are only partly reversible, the strategy supporting the use of a thymidine analogue sparing regimen appears to be the only way to prevent damage that otherwise could be potentially irreversible. However, the quality and benefit of this approach have long been acknowledged in the DHHS guidelines, positioning the association of tenofovir and emtricitabine among the choices recommended for naive patients, for a modern approach to HIV infection therapy.