title: Factors associated with CD8+ T-cell activation in HIV-1-infected patients on long-term antiretroviral therapy.
abstract: BACKGROUND
  Abnormal levels of CD8 T-cell activation persist in HIV-1-infected patients on suppressive antiretroviral therapy (ART) and may be deleterious.
  
  
  METHODS
  CD8 T-cell activation (% coexpressing CD38/HLA-DR) was analyzed on blood specimens from 833 HIV-1-infected patients on ART for ≥96 weeks with concurrent plasma HIV RNA (vRNA) ≤200 copies per milliliter. Factors associated with CD8 T-cell activation were assessed using generalized estimating equations to incorporate longitudinal measurements (median 4/participant).
  
  
  RESULTS
  Participants were 84% men, 47% white, 28% black, and 22% Hispanic, with median pre-ART age 38 years and median ART exposure 144 weeks. CD8 T-cell activation was higher at timepoints when vRNA was 51-200 versus ≤50 copies per milliliter [mean CD8 T-cell activation 23.4% vs. 19.7%; adjusted difference: 1.7% (95% confidence interval: 0.1 to 3.4), P = 0.042]. Restricting to vRNA ≤50 copies per milliliter, multivariable models showed the following factors associated with higher CD8 T-cell activation: older age [≥45 vs. ≤30 years: 3.6% (1.4 to 5.7), P = 0.004], hepatitis C virus antibody positivity [3.6% (0.9 to 6.2), P = 0.032], Hispanic vs. white [7.2% (5.3 to 9.0), P < 0.001], lower concurrent CD4 count [≤200 vs. >500 cells/mm: 2.2% (0.7 to 3.7), P < 0.001], lower concurrent CD4/CD8 ratio [-2.6% (-3.7 to -1.5) per 0.5 unit increase, P < 0.001], and higher pre-ART CD8 T-cell activation [2.0% (1.6 to 2.5) per 10% higher, P < 0.001].
  
  
  CONCLUSIONS
  In participants included in our analysis, residual low-level viremia between 51 and 200 copies per milliliter during ART was shown to be associated with greater CD8 T-cell activation than full suppression to <50 copies per milliliter. Older age, hepatitis C virus antibody positivity, race/ethnicity, higher pre-ART CD8 T-cell activation, and lower concurrent CD4/CD8 ratio and CD4 T-cell count also contribute to greater CD8 T-cell activation during suppressive ART.
authors: *Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; †Division of Infectious Diseases, Northwestern University, Chicago, IL; ‡Division of Infectious Diseases, Massachusetts General Hospital (MGH), Boston, MA; §The Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge, MA; ‖Division of HIV/AIDS, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA; ¶Division of Infectious Diseases; Department of Medicine; University of Washington, Seattle, WA; #Division of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, MD; and **Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA.
authors: Lu
authors: L
authors: Zheng
authors: Babafemi
authors: B
authors: Taiwo
authors: Rajesh T
authors: RT
authors: Gandhi
authors: Peter W
authors: PW
authors: Hunt
authors: Ann C
authors: AC
authors: Collier
authors: Charles
authors: C
authors: Flexner
authors: Ronald J
authors: RJ
authors: Bosch
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000302:isolation & purification; D006684:HLA-DR Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D051997:ADP-ribosyl Cyclase 1; D044966:Anti-Retroviral Agents; C498154:CD38 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D012367:RNA, Viral