title: Protease inhibitor monotherapy is associated with a higher level of monocyte activation, bacterial translocation and inflammation.
abstract: BACKGROUND
  Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation.
  
  
  METHODS
  We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed.
  
  
  RESULTS
  CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16-CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16-CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01).
  
  
  CONCLUSIONS
  Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; btorres@clinic.ub.es.
authors.forename: Berta
authors.initials: B
authors.lastname: Torres
authors.affiliation: Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Lorna
authors.initials: L
authors.lastname: Leal
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Agathe
authors.initials: A
authors.lastname: Leon
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Lucero
authors.affiliation: Department of Clinical Microbiology, Hospital Clínic, CRESIB, University of Barcelona, Barcelona, Spain.
authors.forename: Míriam J
authors.initials: MJ
authors.lastname: Alvarez-Martinez
authors.affiliation: Department of Clinical Microbiology, Hospital Clínic, CRESIB, University of Barcelona, Barcelona, Spain.
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Martinez
authors.affiliation: Department of Clinical Microbiology, Hospital Clínic, CRESIB, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Rebollar
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Cordón
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D018988:Bacterial Translocation; D001777:Blood Coagulation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000453:epidemiology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis; D014766:Viremia; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017320:HIV Protease Inhibitors; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D017452:Receptors, IgG
keywords: immune activation; microbial translocation; monocyte; monotherapy; protease inhibitor; very low-level viremia