TY - JOUR
T1 - Evaluation of the pathogenesis of decreasing CD4 + T cell counts in human immunodeficiency virus type 1-infected patients receiving successfully suppressive antiretroviral therapy
AU - Nies-Kraske, Elizabeth
AU - Schacker, Timothy W.
AU - Condoluci, David
AU - Orenstein, Jan
AU - Brenchley, Jason
AU - Fox, Cecil
AU - Daucher, Marybeth
AU - Dewar, Robin
AU - Urban, Elizabeth
AU - Hill, Brenna
AU - Guenaga, Javier
AU - Hoover, Shelley
AU - Maldarelli, Frank
AU - Hallahan, Claire W.
AU - Horn, Judith
AU - Kottilil, Shyamasundaran
AU - Chun, Tae Wook
AU - Folino, Marlene
AU - Palmer, Sara
AU - Wiegand, Ann
AU - O'Shea, M. Angeline
AU - Metcalf, Julia A.
AU - Douek, Daniel C.
AU - Coffin, John
AU - Haase, Ashley
AU - Fauci, Anthony S.
AU - Dybul, Mark
N1 - Funding Information:
Financial support: National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health (contract N01-CO-12400).
PY - 2009/6/1
Y1 - 2009/6/1
N2 - Most human immunodeficiency virus (HlV)-infected individuals experience increases in peripheral CD4 + T cell counts with suppressive antiretroviral therapy (ART) that achieves plasma HIV RNA levels that are less than the limit of detection. However, some individuals experience decreasing CD4 + T cell counts despite suppression of plasma viremia. We evaluated 4 patients with a history of CD4 + T cell decline despite successfully suppressive ART, from a median of 719 cells/mm3 (range, 360-1141 cells/mm 3) to 227 cells/mm 3 (range, 174-311 cells/mm3) over a period of 18-24 months; 3 of the patients were receiving tenofovir and didanosine, which may have contributed to this decrease. There was no evidence of HIV replication, nor of antiretroviral drug resistance in the blood or lymphoid tissue, or increased proliferation or decreased thymic production of naive CD4 + T cells. All 4 patients had significant fibrosis of the T cell zone of lymphoid tissue, which appeared to be an important factor in the failure to reconstitute T cells.
AB - Most human immunodeficiency virus (HlV)-infected individuals experience increases in peripheral CD4 + T cell counts with suppressive antiretroviral therapy (ART) that achieves plasma HIV RNA levels that are less than the limit of detection. However, some individuals experience decreasing CD4 + T cell counts despite suppression of plasma viremia. We evaluated 4 patients with a history of CD4 + T cell decline despite successfully suppressive ART, from a median of 719 cells/mm3 (range, 360-1141 cells/mm 3) to 227 cells/mm 3 (range, 174-311 cells/mm3) over a period of 18-24 months; 3 of the patients were receiving tenofovir and didanosine, which may have contributed to this decrease. There was no evidence of HIV replication, nor of antiretroviral drug resistance in the blood or lymphoid tissue, or increased proliferation or decreased thymic production of naive CD4 + T cells. All 4 patients had significant fibrosis of the T cell zone of lymphoid tissue, which appeared to be an important factor in the failure to reconstitute T cells.
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U2 - 10.1086/598980
DO - 10.1086/598980
M3 - Article
C2 - 19432547
AN - SCOPUS:67650699827
SN - 0022-1899
VL - 199
SP - 1648
EP - 1656
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -