Switch strategies in patients on effective HAART.

To provide the best possible long-term outcomes for patients, a number of strategies have been proposed based on the possibility to switch from a successful protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) to another antiretroviral regimen. The available evidence from clinical trials in virologically controlled patients demonstrates that switching the PI-based HAART to a simplified regimen is safe. However, abacavir-based simplified therapies should be limited to patients with a known drug history who have not undergone prior mono or dual nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) therapy. Triple NRTI regimens that do not include a thymidine analogue have not been adequately tested so far and are not recommended. The switch strategy may enhance long-term adherence and induce a moderate reduction in cholesterol or amelioration of the total/high-density lipoprotein (HDL) cholesterol ratio that might be particularly relevant for patients presenting other risks for coronary heart disease. Simplified regimens are not associated with a clinically relevant improvement in the redistribution of body fat. Thus, if such a therapeutic strategy is considered, it should be preferably implemented to prevent or delay lipodystrophy. As the therapeutic scenario is significantly changing, in the future, convenience and metabolic alterations will be less of an issue in the decision to use a PI-switch strategy. Future switch strategies may involve NRTIs. Among NRTIs, thymidine analogues and particularly stavudine appear to be most associated with lipoatrophy. NRTI switches may also be beneficial in reducing the risk of lactate level elevation, mitochondrial toxicity, insufficient immunological response to HAART and of selecting class-inducing resistance mutations.