title: Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy.
abstract: OBJECTIVE
  To assess whether T-cell activation independently predicts the extent of CD4(+) T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART).
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38(+)HLA-DR(+)) T cells were measured every 3 months.
  
  
  RESULTS
  Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/μl; and VL, 5.1 log(10) copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre-ART CD8(+) T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8(+) T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048).
  
  
  CONCLUSIONS
  Higher pre-ART CD8(+) T-cell activation independently predicts slower CD4(+) T-cell recovery and higher persistent CD8(+) T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.
authors: Department of Medicine, University of California, San Francisco, USA. phunt@php.ucsf.edu
authors: Peter W
authors: PW
authors: Hunt
authors: Huyen L
authors: HL
authors: Cao
authors: Conrad
authors: C
authors: Muzoora
authors: Isaac
authors: I
authors: Ssewanyana
authors: John
authors: J
authors: Bennett
authors: Nneka
authors: N
authors: Emenyonu
authors: Annet
authors: A
authors: Kembabazi
authors: Torsten B
authors: TB
authors: Neilands
authors: David R
authors: DR
authors: Bangsberg
authors: Steven G
authors: SG
authors: Deeks
authors: Jeffrey N
authors: JN
authors: Martin
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D051997:ADP-ribosyl Cyclase 1