Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy

AIDS. 2011 Nov 13;25(17):2123-31. doi: 10.1097/QAD.0b013e32834c4ac1.


Objectives: 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).

Design: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology*
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Gene Expression / immunology*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / mortality*
  • HIV-1* / drug effects
  • HIV-1* / immunology
  • HIV-1* / isolation & purification
  • Humans
  • Lymphocyte Activation
  • Male
  • Prospective Studies
  • Treatment Outcome
  • Uganda / epidemiology
  • Viral Load


  • Anti-HIV Agents
  • ADP-ribosyl Cyclase 1