Immunologic and virologic events in early HIV infection predict subsequent rate of progression.
BACKGROUND
Variability in human immunodeficiency virus (HIV) disease progression cannot be fully predicted by CD4(+) T cell counts or viral load (VL). Because central memory T (T(CM)) cells play a critical role in the pathogenesis of simian immunodeficiency virus disease, we hypothesized that quantifying these cells in early HIV infection could provide prognostic information.


METHODS
We measured expression of CD45RO, chemokine (C-C motif) receptor (CCR) 5, CCR7, CD27, and CD28 to enumerate naive and memory subsets in samples from recently infected individuals. We also quantified proliferation, CD127 expression, and cell-associated VL. Disease progression was compared across subgroups defined by these measurements, using Kaplan-Meier survival curves and multivariate Cox proportional hazards regression.


RESULTS
Four hundred sixty-six subjects contributed 101 events. The proportion or absolute count of T(CM) cells did not correlate with disease progression, defined as the time to AIDS or death. However, significant associations were observed for proliferation within CD4(+) or CD8(+) T cells, loss of naive or CD127(+) memory CD8(+) T cells, and CD4(+) T cell-associated VL.


CONCLUSIONS
Our results demonstrate that the extent of the immunopathogenesis established early in HIV infection predicts the course of future disease. Because antiretroviral drug treatment reverses such defects in part, our study provides mechanistic clues to why early use of antiretrovirals may prove beneficial.
Ganesan
Anuradha
A
National Naval Medical Center, Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, Maryland 20892, USA.
Chattopadhyay
Pratip K
PK
Brodie
Tess M
TM
Qin
Jing
J
Gu
Wenjuan
W
Mascola
John R
JR
Michael
Nelson L
NL
Follmann
Dean A
DA
Roederer
Mario
M
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D018106:CD28 Antigens / Q000276:immunology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D053208:Kaplan-Meier Estimate; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000276:immunology; D054400:Receptors, CCR7 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D055815:Young Adult
D044966:Anti-Retroviral Agents; C515370:CCR7 protein, human; D018106:CD28 Antigens; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens