Nevirapine Increases High-Density Lipoprotein Cholesterol Concentration by Stimulation of Apolipoprotein A-I Production

Abstract

Objective— The purpose of this study was to investigate the mechanism by which the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) increases high-density lipoprotein cholesterol (HDLc) in treatment-experienced human immunodeficiency virus-1 (HIV-1)–infected patients. Methods and Results— Twelve HIV-1 infected patients, with stably suppressed HIV-1 viral load using AZT/3TC/abacavir for ≥6 months, added NVP to their current antiretroviral regimen. Patients received a primed bolus infusion of the stable isotope L-[1- 13 C]-valine for 12 hours before, as well as 6 and 24 weeks after, the addition of NVP to study apolipoprotein A-I (apoA-I) kinetics. Absolute production rate (APR) and fractional catabolic rate (FCR) of apoA-I were calculated using SAAM-II modeling. Major HDLc-modulating enzymes were assessed. Plasma apoA-I and HDLc levels increased significantly after 24 weeks of treatment by, respectively, 13±4% ( P =0.01) and 16±6% ( P =0.015). Concomitantly, apoA-I production rate at 24 weeks increased by 17±7% ( P =0.04). ApoA-I catabolism did not change. A modest increase of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein activity was observed. Conclusions— NVP increases apoA-I production, which contributes to the HDLc increase after introduction of NVP-containing regimens. In view of the potent antiatherogenic effects of apoA-I, the observed increase may contribute to the favorable cardiovascular profile of NVP.