Activation of CD8 T cells normalizes and correlates with the level of infectious provirus in tonsils during highly active antiretroviral therapy in early HIV-1 infection

Objectives: To study the effects of antiretraviral therapy on T cell activa tion in blood and tonsils from HIV-1 infected individuals in relation to CD 4 cell count, plasma viremia, and infectious HIV-1 provirus. Design: A 48-week study of viral load and T cell subsets in blood and tonsi ls from 12 HIV-1-positive individuals with a mean CD4 cell number of 400 x 10(6) cells/l treated with a combination of zidovudine, lamivudine, and ind inavir. Methods: Tonsil biopsies and blood samples were collected at regular interv als. Lymphocytes were phenotyped and quantified by three-color flow cytomet ry; infectious provirus was quantified by a limiting dilution assay. HIV-l- negative individuals were included as controls. Results: The fraction of tonsillar CD8 T cells expressing CD69, CD38, or HL A-DR in the patients with suppressed virus replication declined to levels c omparable with that in controls by 48 weeks and showed a strong positive co rrelation with tonsillar infectious provirus and plasma viremia. The level of CD4 T cell activation was within normal range in tonsils throughout the study. The fraction of HLA-DR+ cells within CD4 and CD8 T cells in blood de clined rapidly in parallel with plasma viremia but remained slightly higher compared with that in uninfected individuals. Conclusion: Antiretroviral therapy normalizes tonsillar CD8 T cell activati on in HIV-1-positive individuals in parallel with suppression of viral repl ication, indicating reduced CD8 cell turnover. Normal tonsillar CD4 T cell activation suggests limited CD4 cell turnover in early HIV infection. Activ ated CD8 T cells in lymphoid tissue is superior to that in blood as an immu nological marker for the virological response to antiretroviral therapy. (C ) 1999 Lippincott Williams & Wilkins.