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

Hunt, Peter W.a; Cao, Huyen L.a,b,c; Muzoora, Conradd; Ssewanyana, Isaacb; Bennett, Johna; Emenyonu, Nnekad,e; Kembabazi, Annetd; Neilands, Torsten B.a; Bangsberg, David R.d,e; Deeks, Steven G.a; Martin, Jeffrey N.a

doi: 10.1097/QAD.0b013e32834c4ac1
Clinical Science

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 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).

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.

aDepartments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, USA

bJoint Clinical Research Center, Kampala, Uganda

cCA Department of Health Services

dMbarara University of Science and Technology, Uganda

eMassachusetts General Hospital, Harvard School of Medicine, Massachusetts, USA.

Correspondence to Peter W. Hunt, MD, UCSF Positive Health Program, SFGH Building 80, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110 USA. Tel: +1 415 476 4082 x345; fax: +1 415 476-6953; e-mail: phunt@php.ucsf.edu

Received 24 March, 2011

Revised 5 August, 2011

Accepted 24 August, 2011

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© 2011 Lippincott Williams & Wilkins, Inc.