title: Comparative impact of antiretroviral drugs on markers of inflammation and immune activation during the first two years of effective therapy for HIV-1 infection: an observational study.
abstract: BACKGROUND
  Few studies have compared the impact of different antiretroviral regimens on residual immune activation and inflammation with discordant results. Aim of the study was to investigate the impact of various antiretroviral regimens on markers of immune activation and inflammation during the first two years of effective therapy.
  
  
  METHODS
  We studied HIV-infected antiretroviral-naïve patients who began cART with either abacavir/lamivudine or tenofovir/emtricitabine, combined with ritonavir-boosted lopinavir (LPV/r), atazanavir (ATV/r) or efavirenz (EFV). All the patients had a virological response within 6 months, which was maintained for 2 years with no change in their ART regimen. C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), monokine induced by interferon-γ (MIG) and interferon-γ-inducible protein-10 (IP-10) were measured in stored plasma obtained at cART initiation and 24 months later. Mean changes from baseline were analyzed on loge-transformed values and multivariable linear regression models were used to study the effect of the treatment components, after adjusting for factors that might have influenced the choice of ART regimen or biomarker levels. Differences were expressed as the mean fold change percentage difference (Δ).
  
  
  RESULTS
  Seventy-eight patients (91% males) with a median age of 43 years met the inclusion criteria. Their median baseline CD4 cell count was 315/mm3 and HIV-1 RNA level 4.6 log10 copies/ml. During the 2-years study period, IL-6, IP-10 and MIG levels fell significantly, while hs-CRP and sCD14 levels remained stable. IP-10 and MIG levels declined significantly less strongly with ATV/r than with EFV (IP-10Δ -57%, p = 0.011; MIGΔ -136%, p = 0.007), while no difference was noted between LPV/r and EFV. The decline in IL-6 did not differ significantly across the different treatment components.
  
  
  CONCLUSIONS
  After the first 2 years of successful cART, IL-6, IP-10 and MIG fell markedly while hs-CRP and sCD14 levels remained stable. The only impact of ART regimen was a smaller fall in markers of immune activation with ATV/r than with EFV. Our results suggest that these markers could be worthwhile when evaluating new antiretroviral drugs.
authors.affiliation: INSERM, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris F-75013, France. suhaibhattab@yahoo.com.
authors.forename: Suhaib
authors.initials: S
authors.lastname: Hattab
authors.forename: Amelie
authors.initials: A
authors.lastname: Guihot
authors.forename: Marguerite
authors.initials: M
authors.lastname: Guiguet
authors.forename: Slim
authors.initials: S
authors.lastname: Fourati
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Fabienne
authors.initials: F
authors.lastname: Caby
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D054357:Chemokine CXCL10 / Q000097:blood; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D003521:Cyclopropanes; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D009842:Oligopeptides; D011725:Pyridines; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D007371:Interferon-gamma; D002097:C-Reactive Protein; C098320:efavirenz; D019438:Ritonavir