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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1336.)
© 2009 American Heart Association, Inc.

National Cholesterol Awareness Month

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

Remco Franssen; Raaj R. Sankatsing; Elly Hassink; Barbara Hutten; Mariette T. Ackermans; Kees Brinkman; René Oesterholt; Alejandro Arenas-Pinto; Stephen P. Storfer; John J. Kastelein; Hans P. Sauerwein; Peter Reiss; Erik S. Stroes

From the Department of Vascular Medicine (R.F., R.R.S., J.J.K., E.S.S.), the Department of Clinical Epidemiology, Biostatistics, and Bioinformatics (B.H.), the Department of Clinical Chemistry, Laboratory of Endocrinology (M.T.A., R.O.), the Department of Endocrinology and Metabolism (H.P.S.), and the Department of Infectious Disease, Tropical Medicine, and AIDS and the Center for Infection and Immunity Amsterdam (CINIMA) (P.R.), Academic Medical Center, Amsterdam, The Netherlands; IATEC BV (E.H.), Amsterdam, The Netherlands; the Department of Internal Medicine (K.B.), Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands; the Centre for Sexual Health & HIV Research (A.A.-P.), University College London, UK; and Boehringer Ingelheim Pharmaceuticals Inc (S.P.S.), Ridgefield, Conn.

Correspondence to Erik S.G. Stroes, Academic Medical Center, Department of Vascular Medicine, F4.275, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail e.s.stroes{at}amc.uva.nl

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-[1-¹³C]-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.

In this study the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) was shown to increase HDLc in treatment-experienced human immunodeficiency virus-1 infected patients by means of increasing the absolute production rate of apoA-I. This observed increase may contribute to the favorable cardiovascular profile associated with NVP.

Key Words: nevirapine • high-density lipoprotein cholesterol • apolipoprotein A-I • metabolism • stable isotopes