Switching Strategies to Improve Lipid Profile and Morphologic Changes

Metabolic alterations and body fat changes are well-recognized limitations of protease inhibitor-basedregimens. Strategies of replacing protease inhibitors with nonnucleoside reverse transcriptase inhibitorsor abacavir have been shown to improve metabolic abnormalities, particularly by decreasingcholesterol and triglyceride levels, and reducing cardiovascular risk. The various therapeutic optionsshow differences in efficacy, tolerability, and metabolic outcomes. Abacavir seems to be bettertolerated, 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 profilewith a greater increase in HDL cholesterol and in the HDL/total cholesterol ratio, one of the mostimportant parameters associated with a reduction in cardiovascular risk. Efavirenz has been associatedwith 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 strongevidence suggesting a prominent role of thymidine analogs, mainly stavudine, in its development.Substitution of stavudine or zidovudine for abacavir or tenofovir partially improves peripheral fatloss. In addition, the lipid profile significantly improves.Finally, although the extended use of non-thymidine nucleoside analogs and the development of newfamilies of antiretroviral drugs will probably result in a lower impact in lipids and morphologicchanges, many patients are currently under treatment with these compounds. In this setting, switchingstrategies may be useful to minimize clinical and psychological consequences, improving the qualityof life of HIV-infected patients treated with HAART.