title: High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort.
abstract: BACKGROUND
  Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.
  
  
  METHODS
  T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].
  
  
  RESULTS
  Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].
  
  
  CONCLUSIONS
  T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
authors.affiliation: Department of Medicine, Makerere University School of Medicine, Kampala, Uganda. drdamalie@yahoo.com
authors.forename: Damalie
authors.initials: D
authors.lastname: Nakanjako
authors.forename: Isaac
authors.initials: I
authors.lastname: Ssewanyana
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Agnes
authors.initials: A
authors.lastname: Kiragga
authors.forename: Robert
authors.initials: R
authors.lastname: Colebunders
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.forename: Rose
authors.initials: R
authors.lastname: Nabatanzi
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral