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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    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 > 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
    Volume29
    Issue number9
    DOIs
    Publication statusPublished - 1 Jan 2009

    Cite this

    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. https://doi.org/10.1161/ATVBAHA.109.192088