Immunological and Virological Failure after Antiretroviral Therapy Is Associated with Enhanced Peripheral and Thymic Pathogenicity

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T cell dynamics and viral genotype were studied in human immunodeficiency virus 1-infected individuals receiving antiretroviral therapy who were viremic and had either increasing (discordant immunological responders) or decreasing (nonresponders) CD4+ T cell counts. A comparison was made with treated individuals who were not viremic and had increasing CD4+ T cell counts (complete responders). Nonresponders had higher CD4+ T cell proliferation (as assessed by Ki67 expression) and immune activation (as assessed by CD38 and human leukocyte antigen-DR expression), together with a reduction in T cell receptor excision circles, compared with discordant immunological responders and complete responders, which suggests that there is enhanced viral pathogenicity in both peripheral T cells and the thymus. Although there was a high prevalence of mutations in the protease and reverse transcriptase genes in discordant immunological responders, these changes were also observed in nonresponders.

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