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

Full 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.

Author information

Author/s: Franssen, Remco (R); Sankatsing, Raaj R (RR); Hassink, Elly (E); Hutten, Barbara (B); Ackermans, Mariette T (MT); Brinkman, Kees (K); Oesterholt, René (R); Arenas-Pinto, Alejandro (A); Storfer, Stephen P (SP); Kastelein, John J (JJ); Sauerwein, Hans P (HP); Reiss, Peter (P); Stroes, Erik S (ES);

Affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.

Journal and publication information

Publication Type: Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't

Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol), published in United States. (Language: eng)

Reference: 2009-Sep; vol 29 (issue 9) : pp 1336-41

Dates: Created 2009/08/20; Completed 2009/09/08;

PMID: 19667106, status: MEDLINE (last retrieved date: 9/8/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adult
Anti-HIV Agents - therapeutic use
Antiretroviral Therapy, Highly Active
Apolipoprotein A-I - blood
Cholesterol, HDL - blood
Dideoxynucleosides - therapeutic use
HIV Infections - blood; drug therapy; virology
HIV-1 - genetics; isolation & purification
Humans
Kinetics
London

London
Magnetic Resonance Spectroscopy
Male
Middle Aged
Netherlands
Nevirapine - therapeutic use
RNA, Viral - blood
Reverse Transcriptase Inhibitors - therapeutic use
Treatment Outcome
Up-Regulation
Viral Load

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: APOA1 protein, human (0) ; Anti-HIV Agents (0) ; Apolipoprotein A-I (0) ; Cholesterol, HDL (0) ; Dideoxynucleosides (0) ; RNA, Viral (0) ; Reverse Transcriptase Inhibitors (0) ; abacavir (0) ; Nevirapine (129618-40-2)

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