T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication.
BACKGROUND
CD4 T-cell recovery is impeded in some HIVinfected patients despite successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We hypothesized that T-cell dysfunction would be increased in these patients.


METHODS
In the Danish HIV Cohort Study, we identified HIV-1-infected patients initiating cART with a CD4 cell count <100 cells per microliter, followed by HIV RNA <50 copies per milliliter for 3 years. Patients with a CD4 count <200 cells per microliter after 3 years were identified as cases; 42 patients with a CD4 count > or = 200 cells per microliter were selected as controls. Six-color flow cytometry was performed on whole blood. Cytokine levels in supernatants from whole blood stimulations were assessed.


RESULTS
The case and control groups comprised 18 and 35 patients, respectively. Cases were older than controls (median: 54/46 years). The fraction of CD28+ cells was decreased among cases in the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding naive subsets (P = 0.0011/P , 0.0001). Cases had higher expression of human leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028). The production of interleukin (IL)-10 and IL-2 to phytohemagglutinin was decreased in cases (P < 0.0001/P = 0.019).


CONCLUSIONS
Patients with impaired CD4 recovery shared a dysregulated T-cell phenotype with low CD28, high HLA-DR expression, and low IL-2 and IL-10 production.
Erikstrup
Christian
C
Department of Clinical Immunology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. christian@erikstrup.org
Kronborg
Gitte
G
Lohse
Nicolai
N
Ostrowski
Sisse Rye
SR
Gerstoft
Jan
J
Ullum
Henrik
H
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D003718:Denmark; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019562:Viral Load
D019380:Anti-HIV Agents; D018106:CD28 Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D016753:Interleukin-10