HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T…

• DD
  Doris Duke Charitable Foundation
• AT
  amfAR, The Foundation for AIDS Research
• DA
  Delaney AIDS Research Enterprise
• NI
  National Institutes of Health

  Awards: UL1 RR024131, RO1 AI087145, P30 AI027763, K24 AI069994, R24 AI067039, AI027763, RR024131, AI069994, R21 AI087035, U19 AI0961090
• UO
  University of California, San Francisco

  Awards: P30 AI027763, UL1 RR024131
• NI
  National Institute of Mental Health
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: AI027763, RR024131, AI067039, UL1 RR024131, AI071713, AI069994, R24 AI067039, K24 AI069994, P30 AI027763
• CF
  Center for AIDS Prevention Studies, University of California, San Francisco

  Award: P30 MH62246