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

• Published in: AIDS (London) Vol. 25; no. 17; pp. 2123 - 2131
• Main Authors: HUNT, Peter W, CAO, Huyen L, MARTIN, Jeffrey N, MUZOORA, Conrad, SSEWANYANA, Isaac, BENNETT, John, EMENYONU, Nneka, KEMBABAZI, Annet, NEILANDS, Torsten B, BANGSBERG, David R, DEEKS, Steven G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 13.11.2011
• Subjects: ADP-ribosyl Cyclase 1 - immunology; Adult; AIDS/HIV; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; 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; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lymphocyte Activation; Male; Medical sciences; Pharmacology. Drug treatments; Prospective Studies; Treatment Outcome; Uganda - epidemiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Uganda; Sub-Saharan Africa; Africa; Immunopathology; Antiretroviral agent; Prognosis; Mortality; antiretroviral therapy; Retroviridae; AIDS; Immune deficiency; Lentivirus; T-cell activation; Infection; Virus; Chemotherapy; sub-Saharan Africa; Treatment; HIV; Immunological investigation; Viral disease; T-Lymphocyte; Antiviral; Uganda; Human immunodeficiency virus
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32834c4ac1

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 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). 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.