title: Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function.
abstract: OBJECTIVE
  HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional.
  
  
  RESULTS
  Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, low-density lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[(3)H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (P<0.001).
  
  
  CONCLUSIONS
  Compared with NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.
authors: Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Baiba K
authors: BK
authors: Gillard
authors: Joe L
authors: JL
authors: Raya
authors: Raul
authors: R
authors: Ruiz-Esponda
authors: Dinakar
authors: D
authors: Iyer
authors: Ivonne
authors: I
authors: Coraza
authors: Ashok
authors: A
authors: Balasubramanyam
authors: Henry J
authors: HJ
authors: Pownall
mesh_terms: D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D002788:Cholesterol Esters / Q000378:metabolism; D003131:Combined Modality Therapy; D004032:Diet; D015444:Exercise; D058607:Fibric Acids / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced* / Q000628:therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D009525:Niacin / Q000627:therapeutic use; D055550:Protein Stability; D018110:Receptors, Lipoprotein / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D002788:Cholesterol Esters; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D018110:Receptors, Lipoprotein; D014280:Triglycerides; D009525:Niacin
keywords: HIV dyslipidemia; hepatocyte cholesteryl ester uptake; high-density lipoprotein function; lipoprotein composition
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