title: Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.
abstract: Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART).
  
  
  
  A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders.
  
  
  
  After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated.
  
  
  
  When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
authors.affiliation: Hospital Clínico San Carlos-IdiSSC, Universidad Complutense, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Estrada
authors.affiliation: Universidad de Alcalá de Henares, CIBERESP, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Monge
authors.affiliation: Hospital Clínico San Carlos-IdiSSC, Universidad Complutense, Madrid, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Gómez-Garre
authors.affiliation: Universidad de Alcalá de Henares, CIBERESP, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Sobrino
authors.affiliation: Hospital General de Elche, Elche, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Masiá
authors.affiliation: Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Portilla
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Viladés
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.affiliation: Hospital San Pedro-CIBIR, Logroño, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Blanco
mesh_terms: D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood; D054467:Phospholipases A2 / Q000097:blood; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D015415:Biomarkers; D003521:Cyclopropanes; D008077:Lipoproteins, LDL; D000069446:Atazanavir Sulfate; D009195:Peroxidase; D054467:Phospholipases A2; C098320:efavirenz; D001663:Bilirubin
keywords: atazanavir; bilirubin; efavirenz; oxidative stress; prospective studies