AIDS. 25(17):2123–2131, NOVEMBER 13TH, 2011
DOI: 10.1097/QAD.0b013e32834c4ac1
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PMID: 21881481
Issn Print: 0269-9370
Publication Date: November 13th, 2011
Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy
Peter Hunt;Huyen Cao;Conrad Muzoora;Isaac Ssewanyana;John Bennett;Nneka Emenyonu;Annet Kembabazi;Torsten Neilands;David Bangsberg;Steven Deeks;Jeffrey Martin;
+ Author Information
aDepartments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, USAbJoint Clinical Research Center, Kampala, UgandacCA Department of Health ServicesdMbarara University of Science and Technology, UgandaeMassachusetts General Hospital, Harvard School of Medicine, Massachusetts, USA.
Abstract
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).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 (CD38+HLA-DR+) 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/μl; 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 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).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.
