Evaluation of the pathogenesis of decreasing CD4(+) T cell counts in human immunodeficiency virus type 1-infected patients receiving successfully suppressive antiretroviral therapy.
Most human immunodeficiency virus (HIV)-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/mm(3) (range, 360-1141 cells/mm(3)) to 227 cells/mm(3) (range, 174-311 cells/mm(3)) 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.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Elizabeth
E
Nies-Kraske
Timothy W
TW
Schacker
David
D
Condoluci
Jan
J
Orenstein
Jason
J
Brenchley
Cecil
C
Fox
Marybeth
M
Daucher
Robin
R
Dewar
Elizabeth
E
Urban
Brenna
B
Hill
Javier
J
Guenaga
Shelley
S
Hoover
Frank
F
Maldarelli
Claire W
CW
Hallahan
Judith
J
Horn
Shyamasundaran
S
Kottilil
Tae-Wook
TW
Chun
Marlene
M
Folino
Sara
S
Palmer
Ann
A
Wiegand
M Angeline
MA
O'Shea
Julia A
JA
Metcalf
Daniel C
DC
Douek
John
J
Coffin
Ashley
A
Haase
Anthony S
AS
Fauci
Mark
M
Dybul
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D004279:DNA, Viral / Q000235:genetics; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D013950:Thymus Gland / Q000276:immunology; D019562:Viral Load
D004279:DNA, Viral; D012367:RNA, Viral