Nevirapine increases high-density lipoprotein cholesterol concentration by stimulation of apolipoprotein A-I production

R. Franssen, R.R. Sankatsing, E. Hassink, B. Hutten, M.T. Ackermans, K. Brinkman, R. Oesterholt, A. Arenas Pinto, S.P. Storfer, J.J. Kastelein, H.P. Sauerwein, P. Reiss, E.S. Stroes

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    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 > or =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.
    Original languageEnglish
    Pages (from-to)1336-41
    JournalArteriosclerosis Thrombosis and Vascular Biology
    Issue number9
    Publication statusPublished - 1 Jan 2009

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    Franssen, R., Sankatsing, R. R., Hassink, E., Hutten, B., Ackermans, M. T., Brinkman, K., Oesterholt, R., Arenas Pinto, A., Storfer, S. P., Kastelein, J. J., Sauerwein, H. P., Reiss, P., & Stroes, E. S. (2009). Nevirapine increases high-density lipoprotein cholesterol concentration by stimulation of apolipoprotein A-I production. Arteriosclerosis Thrombosis and Vascular Biology, 29(9), 1336-41.