Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load.
Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation "set point" is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4+ and CD8+ T cells was measured longitudinally in 68 antiretroviral-untreated individuals and 83 antiretroviral-treated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8+ T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10,000 copies/mL. Among untreated patients, the level of CD8+ T-cell activation varied widely among individuals but often remained stable within a given individual. CD8+ T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4+ T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4+ T cells are lost over time.
Deeks
Steven G
SG
San Francisco General Hospital, 995 Potrero Ave, San Francisco, CA 94110, USA. sdeeks@php.ucsf.edu
Kitchen
Christina M R
CM
Liu
Lea
L
Guo
Hua
H
Gascon
Ron
R
Narváez
Amy B
AB
Hunt
Peter
P
Martin
Jeffrey N
JN
Kahn
James O
JO
Levy
Jay
J
McGrath
Michael S
MS
Hecht
Frederick M
FM
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D012367:RNA, Viral