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.
Nies-Kraske
Elizabeth
E
National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Schacker
Timothy W
TW
Condoluci
David
D
Orenstein
Jan
J
Brenchley
Jason
J
Fox
Cecil
C
Daucher
Marybeth
M
Dewar
Robin
R
Urban
Elizabeth
E
Hill
Brenna
B
Guenaga
Javier
J
Hoover
Shelley
S
Maldarelli
Frank
F
Hallahan
Claire W
CW
Horn
Judith
J
Kottilil
Shyamasundaran
S
Chun
Tae-Wook
TW
Folino
Marlene
M
Palmer
Sara
S
Wiegand
Ann
A
O'Shea
M Angeline
MA
Metcalf
Julia A
JA
Douek
Daniel C
DC
Coffin
John
J
Haase
Ashley
A
Fauci
Anthony S
AS
Dybul
Mark
M
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