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Clin Infect Dis. 2011 Nov;53(9):944-51. doi: 10.1093/cid/cir552. Epub 2011 Sep 29.

Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy.

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  • 1Department of Infectious Disease, Peking Union Medical College Hospital, and Chinese Academy of Medical Sciences, Beijing, China. litsh@263.net

Abstract

BACKGROUND:

Approximately 20% of human immunodeficiency virus type 1 (HIV-1)--infected adults do not normalize their CD4(+) T lymphocytes after long-term effective highly active antiretroviral therapy (HAART). The mechanistic basis for this failure is unclear.

METHODS:

Seventy-four patients were followed up regularly for 3-7 years. Patients with undetectable plasma viral load (<50 copies/mL) for over 12 months were further classified into 2 groups: (1) immunological nonresponders, whose CD4(+) T-cell count was < 200/μL or <20% compared with baseline; and (2) immunological responders, whose CD4(+) T-cell count was > 300/μL or >30% compared with baseline.

RESULTS:

Compared with 17 immunological responders, 13 immunological nonresponders had a lower magnitude of naive CD4(+) T-cell increase, a lower percentage of recent thymic immigrants (CD31(+)%), and a higher percentage of activated CD8(+) T cells. Furthermore, unlike CD4(+) T cells, which increased along with the decrease of viral load, the percentage of recent thymic immigrants (CD31(+)%) had little change in the majority of patients. These data were fit into a mathematical model, , from which we deduced that the initial rate of CD4(+) T-cell restoration is associated significantly with the percentage of recent thymic immigrants (CD31(+)%).

CONCLUSIONS:

Our data indicate that the failure to restore CD4(+) T-cell count following HAART was associated primarily with a defect in recent thymic immigrants, which suggests the existence of thymus exhaustion.

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