title: Nevirapine increases high-density lipoprotein cholesterol concentration by stimulation of apolipoprotein A-I production.
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.
  
  
  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.
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Remco
authors: R
authors: Franssen
authors: Raaj R
authors: RR
authors: Sankatsing
authors: Elly
authors: E
authors: Hassink
authors: Barbara
authors: B
authors: Hutten
authors: Mariette T
authors: MT
authors: Ackermans
authors: Kees
authors: K
authors: Brinkman
authors: René
authors: R
authors: Oesterholt
authors: Alejandro
authors: A
authors: Arenas-Pinto
authors: Stephen P
authors: SP
authors: Storfer
authors: John J
authors: JJ
authors: Kastelein
authors: Hans P
authors: HP
authors: Sauerwein
authors: Peter
authors: P
authors: Reiss
authors: Erik S
authors: ES
authors: Stroes
mesh_terms: 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
chemical_list: 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