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


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.
Franssen
Remco
R
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
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
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D016632:Apolipoprotein A-I / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D015224:Dideoxynucleosides / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007700:Kinetics; D008131:London; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D019829:Nevirapine / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D015854:Up-Regulation; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D015224:Dideoxynucleosides; D019829:Nevirapine; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C505693:APOA1 protein, human