Reversal of Atherogenic Lipoprotein Profile in HIV-1 Infected Patients with Lipodystrophy After Replacing Protease Inhibitors by Nevirapine

Background: The widespread use of protease inhibitors (PI) has been associated with abnormalities in the lipid profile of HIV-1-infected patients. Treatment simplification approaches in which PI are replaced by nevirapine (NVP) have been shown to improve PI-related toxicity.

Objective: To assess the impact on plasma lipids of replacing the PI by NVP in HIV-1 infected patients with lipodystrophy.

Methods: We studied 34 patients with lipodystrophy who had been the first to be enrolled in a prospective, randomized trial of continuing current treatment, or replacing PI with NVP. Sixteen patients replaced their PI with NVP and 18 continued their current PI-containing treatment. Total, low density lipoprotein (LDL), very low density lipoprotein (VLDL), intermediate density lipoprotein and high density lipoprotein (HDL) cholesterol and triglyceride levels, the size and particle number of LDL were determined at baseline and after 24 weeks, by nucleic magnetic resonance spectroscopy.

Findings: After 24 weeks of replacing the PI with NVP, we observed a reduction of total cholesterol (P = 0.028), LDL-cholesterol (P = 0.001), the number of circulating LDL particles (P = 0.003) and the VLDL-1 triglyceride level (P = 0.032). A concomitant significant increase was observed in both HDL-cholesterol level (P = 0.002) and HDL particle size (P < 0.001). No significant changes were observed in the group that continued taking the PI.

Conclusions: The replacement of PI by NVP improved the lipid profile both by reducing the number and lipid content of atherogenic LDL particles, and increasing the protective HDL fraction. Although total triglyceride levels remained unchanged, a reduction in the VLDL-1 fraction contributes to the reduction of LDL particles. These changes are expected to reduce the risk of cardiovascular disease in HIV-1-infected patients on highly active antiretroviral therapy.