title: Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV-1-infected individuals.
abstract: OBJECTIVE
  Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips.
  
  
  METHODS
  HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients.
  
  
  RESULTS
  Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/μL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46).
  
  
  CONCLUSIONS
  The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.
authors.affiliation: Department of Medicine 1/Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zoufaly
authors.forename: J G
authors.initials: JG
authors.lastname: Kiepe
authors.forename: S
authors.initials: S
authors.lastname: Hertling
authors.forename: A
authors.initials: A
authors.lastname: Hüfner
authors.forename: O
authors.initials: O
authors.lastname: Degen
authors.forename: T
authors.initials: T
authors.lastname: Feldt
authors.forename: S
authors.initials: S
authors.lastname: Schmiedel
authors.forename: M
authors.initials: M
authors.lastname: Kurowski
authors.forename: J
authors.initials: J
authors.lastname: van Lunzen
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D006684:HLA-DR Antigens; D002097:C-Reactive Protein
keywords: HIV infection; HIV viraemia; immune activation; viral blips