title: Impact of peginterferon alpha and ribavirin treatment on lipid profiles and insulin resistance in Hepatitis C virus/HIV-coinfected persons: the AIDS Clinical Trials Group A5178 Study.
abstract: BACKGROUND
  The effect of peginterferon alpha/ribavirin (PEG-IFN/RBV) and hepatitis C virus (HCV) clearance on lipid and insulin resistance (IR) profiles in HCV/human immunodeficiency virus (HIV) coinfection is unknown.
  
  
  METHODS
  We measured fasting total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoproteins (HDL-C), triglycerides (TG), glucose, and insulin at defined intervals in the A5178 study (N = 329), a prospective treatment trial in HCV/HIV coinfection. Changes from baseline and the relation between baseline values of these variables to sustained virologic response (SVR) were determined.
  
  
  RESULTS
  Of 182 subjects with metabolic data, 98 achieved early virologic response (EVR) and continued PEG-IFN/RBV. Among those, median pretreatment HCV RNA was 6.6 log(10 )IU/mL; 73% had HCV genotype 1. Median pretreatment TC was 176 mg/dL (interquartile range [IQR],150-205]; median LDL-C was 99 mg/dL (IQR, 79-123); median HDL-C was 40 mg/dL (IQR, 31-47); and median TG was 147 mg/dL (IQR, 101-221). Median homeostasis model assessment of IR (HOMA-IR) was 3.3 (IQR, 1.7-5.3). The EVRs demonstrated a decline in TC, LDL-C, and HDL-C, whereas TG increased on treatment but returned to near baseline 24 weeks after end of treatment (EOT). The HOMA-IR decline from entry to 24 weeks after EOT was significant among non-sustained virologic responders and nonsignificant among sustained virologic responders; this difference was offset after adjusting for higher HOMA-IR at baseline among the former. Among all 182 subjects, entry LDL-C was associated with SVR in a joint logistic model adjusted for HCV genotype, race, and prior IFN (odds ratio, 1.17 per 10 mg/dL increase; 95% confidence interval, 1.03-1.32), but TC, HDL, TG, and IR were not.
  
  
  CONCLUSIONS
  Peginterferon alpha and RBV can significantly affect lipid profile and IR in HCV/HIV-coinfected persons. Although the lipid profile returns to near pretreatment levels after completion of treatment, our data suggest persistent modest improvement in IR with treatment. Clinical Trials Registration. NCT00078403.
authors.affiliation: University of Pittsburgh School of Medicine, PA 15213, USA. aabutt@pitt.edu
authors.forename: Adeel A
authors.initials: AA
authors.lastname: Butt
authors.forename: Triin
authors.initials: T
authors.lastname: Umbleja
authors.forename: Janet W
authors.initials: JW
authors.lastname: Andersen
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use; D060085:Coinfection / Q000097:blood / Q000188:drug therapy / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007333:Insulin Resistance; D016898:Interferon-alpha / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D008074:Lipoproteins; D011092:Polyethylene Glycols; D012254:Ribavirin