Hunt P.W., Cao H.L., Muzoora C., Ssewanyana I., Bennett J., Emenyonu N., Kembabazi A., Neilands T.B., Bangsberg D.R., Deeks S.G., Martin J.N.
Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States; Joint Clinical Research Center, Kampala, Uganda; CA Department of Health Services, Uganda; Mbarara University of Science and Technology, Uganda; Massachusetts General Hospital, Harvard School of Medicine, MA, United States
Hunt, P.W., Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States; Cao, H.L., Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States, Joint Clinical Research Center, Kampala, Uganda, CA Department of Health Services, Uganda; Muzoora, C., Mbarara University of Science and Technology, Uganda; Ssewanyana, I., Joint Clinical Research Center, Kampala, Uganda; Bennett, J., Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States; Emenyonu, N., Mbarara University of Science and Technology, Uganda, Massachusetts General Hospital, Harvard School of Medicine, MA, United States; Kembabazi, A., Mbarara University of Science and Technology, Uganda; Neilands, T.B., Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States; Bangsberg, D.R., Mbarara University of Science and Technology, Uganda, Massachusetts General Hospital, Harvard School of Medicine, MA, United States; Deeks, S.G., Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States; Martin, J.N., Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, United States
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 (CD38HLA-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. © 2011 Wolters Kluwer Health Lippincott Williams & Wilkins.