title: Evaluation of cardiovascular biomarkers in a randomized trial of fosamprenavir/ritonavir vs. efavirenz with abacavir/lamivudine in underrepresented, antiretroviral-naïve, HIV-infected patients (SUPPORT): 96-week results.
abstract: BACKGROUND
  Rates of cardiovascular disease are higher among HIV-infected patients as a result of the complex interplay between traditional risk factors, HIV-related inflammatory and immunologic changes, and effects of antiretroviral therapy (ART). This study prospectively evaluated changes in cardiovascular biomarkers in an underrepresented, racially diverse, HIV-1-infected population receiving abacavir/lamivudine as backbone therapy.
  
  
  METHODS
  This 96-week, open-label, randomized, multicenter study compared once-daily fosamprenavir/ritonavir 1400/100 mg and efavirenz 600 mg, both with ABC/3TC 600 mg/300 mg, in antiretroviral-naïve, HLA-B*5701-negative adults without major resistance mutations to study drugs. We evaluated changes from baseline to weeks 4, 12, 24, 48, and 96 in interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), d-dimer, plasminogen, and fibrinogen. Biomarker data were log-transformed before analysis, and changes from baseline were described using geometric mean ratios.
  
  
  RESULTS
  This study enrolled 101 patients (51 receiving fosamprenavir/ritonavir; 50 receiving efavirenz): 32% female, 60% African American, and 38% Hispanic/Latino; 66% (67/101) completed 96 weeks on study. At week 96, levels of IL-6, sVCAM-1, d-dimer, fibrinogen, and plasminogen were lower than baseline in both treatment groups, and the decrease was statistically significant for sVCAM-1 (fosamprenavir/ritonavir and efavirenz), d-dimer (fosamprenavir/ritonavir and efavirenz), fibrinogen (efavirenz), and plasminogen (efavirenz). Values of hs-CRP varied over time in both groups, with a significant increase over baseline at Weeks 4 and 24 in the efavirenz group. At week 96, there was no difference between the groups in the percentage of patients with HIV-1 RNA <50 copies/mL (fosamprenavir/ritonavir 63%; efavirenz 66%) by ITT missing-equals-failure analysis. Treatment-related grade 2-4 adverse events were more common with efavirenz (32%) compared with fosamprenavir/ritonavir (20%), and median lipid concentrations increased in both groups over 96 weeks of treatment.
  
  
  CONCLUSIONS
  In this study of underrepresented patients, treatment with abacavir/lamivudine combined with either fosamprenavir/ritonavir or efavirenz over 96 weeks, produced stable or declining biomarker levels except for hs-CRP, including significant and favorable decreases in thrombotic activity (reflected by d-dimer) and endothelial activation (reflected by sVCAM-1). Our study adds to the emerging data that some cardiovascular biomarkers are decreased with initiation of ART and control of HIV viremia.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00727597.
authors.forename: Princy
authors.initials: P
authors.lastname: Kumar
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Gregory
authors.initials: G
authors.lastname: Huhn
authors.forename: Louis
authors.initials: L
authors.lastname: Sloan
authors.forename: Catherine Butkus
authors.initials: CB
authors.lastname: Small
authors.forename: Howard
authors.initials: H
authors.lastname: Edelstein
authors.forename: Franco
authors.initials: F
authors.lastname: Felizarta
authors.forename: Ritche
authors.initials: R
authors.lastname: Hao
authors.forename: Lisa
authors.initials: L
authors.lastname: Ross
authors.forename: Britt
authors.initials: B
authors.lastname: Stancil
authors.forename: Keith
authors.initials: K
authors.lastname: Pappa
authors.forename: Belinda
authors.initials: B
authors.lastname: Ha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002219:Carbamates / Q000627:therapeutic use*; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005663:Furans; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000627:therapeutic use*; D010958:Plasminogen / Q000378:metabolism; D011446:Prospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D015415:Biomarkers; D002097:C-Reactive Protein; D002219:Carbamates; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D004338:Drug Combinations; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D005663:Furans; D015850:Interleukin-6; D019259:Lamivudine; D010755:Organophosphates; D010958:Plasminogen; D019438:Ritonavir; D013449:Sulfonamides; D019010:Vascular Cell Adhesion Molecule-1; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir; C036309:fibrin fragment D; C098320:efavirenz; C426859:fosamprenavir