Incomplete CD4 T Cell Recovery in HIV-1 Infection After 12 Months of Highly Active Antiretroviral Therapy Is Associated With Ongoing Increased CD4 T Cell Activation and Turnover

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Summary:To evaluate the relationship between T cell turnover, immune activation, and CD4 recovery in HIV infection, 32 antiretroviral-naive HIV-1-infected patients were studied before and after initiation of highly active antiretroviral therapy (HAART). Elevated CD4 and CD8 T cell turnover (measured by Ki67) in HIV infection decreased with HAART in blood and lymphoid tissue. Increased peripheral CD4 T cell turnover was strongly associated with immune activation even after viral suppression to less than 50 copies/mL (R = 0.8; p < .001). Increased CD4 T cell turnover correlated strongly with CD4 cell counts both before (R = -0.6; p < .001) and after (R = -0.4; p = .05) HAART. In patients with baseline CD4 cell counts of less than 350/μL, decreases in CD4 T cell turnover with HAART significantly correlated with increases in CD4 cell counts. In addition, persistently elevated levels of CD4 T cell turnover after HAART were associated with incomplete CD4 T cell recovery despite HIV RNA levels of less than 50 copies/mL. These data suggest that immune activation is central to CD4 cell depletion in HIV infection and immune reconstitution with HAART. Address correspondence and reprint requests to Irini Sereti, Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 11B05, Bethesda, MD 20892. E-mail: isereti@niaid.nih.gov Manuscript received October 30, 2002; accepted March 3, 2003. © 2003 Lippincott Williams & Wilkins, Inc.

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