Switching strategies to improve lipid profile and morphologic changes

Metabolic alterations and body fat changes are well-recognized limitations of protease inhibitor-based regimens. Strategies of replacing protease inhibitors with nonnucleoside reverse transcriptase inhibitors or abacavir have been shown to improve metabolic abnormalities, particularly by decreasing cholesterol and triglyceride levels, and reducing cardiovascular risk. The various therapeutic options show differences in efficacy, tolerability, and metabolic outcomes. Abacavir seems to be better tolerated, at least in the only randomized trial in which the three options were compared face-to-face, but it is associated with higher virologic failure in patients with prior suboptimal nucleoside therapy. Nonnucleoside reverse transcriptase inhibitors, particularly nevirapine, result in a better lipid profile with a greater increase in HDL cholesterol and in the HDUtotal cholesterol ratio, one of the most important parameters associated with a reduction in cardiovascular risk. Efavirenz has been associated with increased triglyceride levels in some studies. Although protease inhibitor compounds as a family have been linked to metabolic and body fat alterations, new drugs such as atazanavir seem to be associated with a more favorable lipid profile. Lipoatrophy is a stigmatizing complication in HIV-infected patients receiving HAART. There is strong evidence suggesting a prominent role of thymidine analogs, mainly stavudine, in its development. Substitution of stavudine or zidovudine for abacavir or tenofovir partially improves peripheral fat loss. In addition, the lipid profile significantly improves. Finally, although the extended use of non-thymidine nucleoside analogs and the development of new families of antiretroviral drugs will probably result in a lower impact in lipids and morphologic changes, many patients are currently under treatment with these compounds. In this setting, switching strategies may be useful to minimize clinical and psychological consequences, improving the quality of life of HIV-infected patients treated with HAART.