title: Inflammatory biomarker changes and their correlation with Framingham cardiovascular risk and lipid changes in antiretroviral-naive HIV-infected patients treated for 144 weeks with abacavir/lamivudine/atazanavir with or without ritonavir in ARIES.
abstract: Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of <6% or ≥6%, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were assessed at baseline, week 84, and week 144. Biomarkers were stratified by FRS category. When ritonavir-boosted/nonboosted treatment groups were combined, median hsCRP did not change significantly between baseline (1.6 mg/liter) and week 144 (1.4 mg/liter) in subjects with FRS <6% (p=0.535) or with FRS ≥6% (1.9 mg/liter vs. 2.0 mg/liter, respectively; p=0.102). Median IL-6 was similar for subjects with FRS <6% (p=0.267) at baseline (1.6 pg/ml) and week 144 (1.4 pg/ml) and for FRS ≥6% (2.0 pg/ml vs. 2.2 pg/ml, respectively; p=0.099). Median Lp-PLA(2) decreased significantly (p<0.001) between baseline (197 nmol/min/ml) and week 144 (168 nmol/min/ml) in subjects with FRS <6% and with FRS ≥6% (238 nmol/min/ml vs. 175 nmol/min/ml, respectively; p<0.001). In conclusion, in antiretroviral-naive subjects treated with abacavir-based therapy for 144 weeks, median inflammatory biomarker levels for hsCRP and IL-6 generally remained stable with no significant difference between baseline and week 144 for subjects with either FRS <6% or FRS ≥6%. Lp-PLA(2) median values declined significantly over 144 weeks for subjects in either FRS stratum.
authors.affiliation: Apex Family Medicine and Research, Denver, Colorado 80209, USA. byoung@apexresearchllc.org
authors.forename: Benjamin
authors.initials: B
authors.lastname: Young
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Squires
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Ross
authors.forename: Lizette
authors.initials: L
authors.lastname: Santiago
authors.forename: Louis M
authors.initials: LM
authors.lastname: Sloan
authors.forename: Henry H
authors.initials: HH
authors.lastname: Zhao
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wine
authors.forename: Gary E
authors.initials: GE
authors.lastname: Pakes
authors.forename: David A
authors.initials: DA
authors.lastname: Margolis
authors.forename: Mark S
authors.initials: MS
authors.lastname: Shaefer
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000069446:Atazanavir Sulfate; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003327:Coronary Disease / Q000453:epidemiology*; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D019259:Lamivudine / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D018570:Risk Assessment; D019438:Ritonavir / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult; D000099227:Abacavir
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D015415:Biomarkers; D002097:C-Reactive Protein; D015224:Dideoxynucleosides; D004338:Drug Combinations; D015850:Interleukin-6; D019259:Lamivudine; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D019438:Ritonavir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir