Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function.
OBJECTIVE
To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART).


METHODS
Cross-sectional study of patients with CD4 T cell rises of > or = 200 x 10(6) cells/l (CD4 responders; n = 10) or < 100 x 10(6) cells/l (poor responders; n = 12) in the first year of therapy.


RESULTS
Poor responders were older than CD4 responders (46 versus 38 years; P < 0.01) and, before HAART, had higher CD4 cell counts (170 versus 35 x 106 cells/l; P = 0.11) and CD8 cell counts (780 versus 536 x 10(6) cells/l; P = 0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44 x 10(6) cells/l; P = 0.001) and naive phenotype CD8 cells (487 versus 174 x 10(6) cells/l; P = 0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P = 0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5 x 10(6) cells/l; P = 0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P = 0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics.


CONCLUSIONS
Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.
Teixeira
L
L
Division of Infectious Diseases and the Center for AIDS Research, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106, USA.
Valdez
H
H
McCune
J M
JM
Koup
R A
RA
Badley
A D
AD
Hellerstein
M K
MK
Napolitano
L A
LA
Douek
D C
DC
Mbisa
G
G
Deeks
S
S
Harris
J M
JM
Barbour
J D
JD
Gross
B H
BH
Francis
I R
IR
Halvorsen
R
R
Asaad
R
R
Lederman
M M
MM
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D016615:Telomere / Q000235:genetics; D013950:Thymus Gland / Q000502:physiology*; D014779:Virus Replication