Impact of CD8R T-cell activation on CD4R T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy
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Date
2011
Journal Title
Journal ISSN
Volume Title
Publisher
AIDS (London, England)
Abstract
To assess whether T-cell activation independently predicts the extent of CD4þ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART).
Prospective cohort study.
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 (CD38þHLA-DRþ) T cells were measured every 3 months.
Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/ml; and VL, 5.1 log10 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 CD8þ T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P¼0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8þ 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 (P¼0.048).
Higher pre-ART CD8þ T-cell activation independently predicts slower CD4þ T-cell recovery and higher persistent CD8þ 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.
Description
Keywords
Antiretroviral therapy, HIV, Mortality, Sub-Saharan Africa, T-cell activation, Uganda
Citation
Hunt, P. W., Cao, H. L., Muzoora, C., Ssewanyana, I., Bennett, J., Emenyonu, N., ... & Martin, J. N. (2011). Impact of CD8+ T cell activation on CD4+ T cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS (London, England), 25(17), 2123. DOI:10.1097/QAD.0b013e32834c4ac1