CD4+ T cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapy.
T cell dynamics were studied in human immunodeficiency virus-infected patients who continued using antiretroviral therapy despite detectable plasma viremia (RNA copies >2500 /mL). CD4(+) cell fractional replacement rates, measured by the deuterated glucose technique, were lower in treated patients with detectable viremia than in untreated patients and were similar to those in patients with undetectable viremia. Cell cycle and activation markers exhibited similar trends. For any level of viremia, CD4(+) cell fractional replacement rates were lower in patients with drug-resistant virus than in patients with wild-type virus, which suggests that the resistant variant was less virulent. Interruption of treatment in patients with drug-resistant viremia resulted in increased CD4(+) cell activation, increased CD4(+) cell turnover, and decreased CD4(+) cell counts. These data indicate that partial virus suppression reduces CD4(+) cell turnover and activation, thereby resulting in sustained CD4(+) cell gains, and that measurements of T cell dynamics may provide an in vivo marker of viral virulence.
Deeks
Steven G
SG
Department of Medicine, University of California at San Francisco and San Francisco General Hospital, San Francisco, CA 94110, USA. sdeeks@php.ucsf.edu
Hoh
Rebecca
R
Grant
Robert M
RM
Wrin
Terri
T
Barbour
Jason D
JD
Narvaez
Amy
A
Cesar
Denise
D
Abe
Ken
K
Hanley
Mary Beth
MB
Hellmann
Nicholas S
NS
Petropoulos
Christos J
CJ
McCune
Joseph M
JM
Hellerstein
Marc K
MK
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002453:Cell Cycle; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000276:immunology*
D017320:HIV Protease Inhibitors; D012367:RNA, Viral