title: Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir.
abstract: BACKGROUND
  The effect of specific antiretrovirals on inflammation is unclear.
  
  
  METHODS
  A5224s was a substudy of A5202, which randomized HIV-infected treatment-naïve patients to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir/ritonavir (ATV/r) in a factorial design. Our analysis compared changes in inflammation markers from baseline to week 24 between ABC/3TC and TDF/FTC. Secondary analyses included changes at week 96 and comparisons of EFV vs. ATV/r.
  
  
  RESULTS
  Analyses included 244 patients (85% male, 48% white non-Hispanic), median age 39 years, HIV-1 RNA 4.6 log10 copies/ml, CD4 240 cells/μl. TNF-α, soluble receptors of TNF-α (sTNFR)-I and II, soluble vascular cellular adhesion molecule (sVCAM)-1 and soluble intercellular adhesion molecule (sICAM)-1 decreased significantly at weeks 24 and 96, without significant differences between components (P ≥ 0.44). At week 24, ABC/3TC had a greater high-sensitivity C-reactive protein (hsCRP) mean fold change than TDF/FTC {1.43 vs. 0.88, estimated mean fold change percentage difference [Δ] 61.5% [95% confidence interval (CI) 13.6%, 129.5%]; P = 0.008}. Similar results were seen at week 96 (P = 0.021). At week 24 (but not 96), EFV had a greater hsCRP mean fold change than ATV/r [1.41 vs. 0.88; Δ = 60.2% (12.6%, 127.7%); P = 0.009]. IL-6 decreased significantly at week 24 with TDF/FTC but not with ABC/3TC (between-components P = 0.019). At week 96, IL-6 decreased significantly in both nucleoside reverse transcriptase inhibitor components (between-components P = 0.11). IL-6 changes were not significantly different between ATV/r and EFV at either time point (P ≥ 0.89).
  
  
  CONCLUSIONS
  Soluble TNF-receptors and adhesion molecules decreased following treatment initiation and did not differ by regimens. Differences were seen on hsCRP and IL-6 changes with ABC/3TC vs. TDF/FTC and on hsCRP with EFV vs. ATV/r.
authors.affiliation: Case Western Reserve University and Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA. grace.mccomsey@case.edu
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Douglas
authors.initials: D
authors.lastname: Kitch
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Nasreen C
authors.initials: NC
authors.lastname: Jahed
authors.forename: Kathleen
authors.initials: K
authors.lastname: Melbourne
authors.forename: Belinda
authors.initials: B
authors.lastname: Ha
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.forename: Anthony
authors.initials: A
authors.lastname: Bloom
authors.forename: Neal
authors.initials: N
authors.lastname: Fedarko
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism*; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000494:pharmacology; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood*; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology; D000068698:Tenofovir; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000187:drug effects; D000099227:Abacavir
chemical_list: D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D015415:Biomarkers; D002097:C-Reactive Protein; D003521:Cyclopropanes; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D015850:Interleukin-6; D019259:Lamivudine; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D019438:Ritonavir; D000068698:Tenofovir; D014409:Tumor Necrosis Factor-alpha; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir; C098320:efavirenz