February 7, 2001
While the deleterious effect of protease inhibitors on blood lipid levels is well known, much less is known about the effects of NNRTIs. In this sub-study of blood samples taken from the Atlantic Study, nevirapine is shown to have potentially cardio-protective effects on plasma lipids.
The Atlantic study randomized antiretroviral therapy-naive, asymptomatic HIV-positive patients to d4T/ddI plus one of indinavir, 3TC, or nevirapine. For the lipid analysis, patients were required to be on their assigned study medication for at least 24 weeks, and also to have two aliqots of stored plasma available at week 0, 6, and 24. Overall, 114 out of the 298 patients in Atlantic met these criteria. Measurements included a comprehensive analysis of not only cholesterol and triglycerides, but also lipoprotein subclasses.
The investigators found that although nevirapine treatment was associated with a small increase in LDL cholesterol, this was more than offset by a striking 38% increase in HDL cholesterol -- the "good" cholesterol known to be associated with lower cardiovascular risk. Improvements were also seen in HDL particle size and lipoprotein A1. A significant but smaller effect was also seen in the 3TC arm of the study, but not of the same magnitude, while no beneficial lipid changes occurred in the indinavir arm. The study investigators concluded that the favorable shifting of the total cholesterol/HDL ratio seen in the nevirapine arm of the study could confer significant benefit if maintained over a prolonged period of time.
The results of this study are similar to some other reports of efavirenz-induced increases in total and HDL cholesterol, and suggest a possible class effect related either to the structure of these NNRTIs or perhaps their similar effect on the cytochrome p450 system. The ultimate clinical implications of NNRTI-induced changes in plasma lipids remain uncertain, and will bear close watching.
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