T cell activation in HIV-seropositive Ugandans: differential associations with viral load, CD4+ T cell depletion, and coinfection.
Immune activation is thought to play a major role in the pathogenesis of human immunodeficiency virus (HIV). This effect may be particularly relevant in Africa, where endemic coinfections may contribute to disease progression, perhaps as a consequence of enhanced immune activation. We investigated the expression of CD38 and human leukocyte antigen (HLA)-DR on T cells in 168 HIV-seropositive volunteers in Uganda. We observed higher levels of CD4(+) and CD8(+) T cell activation in Uganda, compared with those reported in previous studies from Western countries. Coexpression of CD38 and HLA-DR on both CD4(+) and CD8(+) T cell subsets was directly correlated with viral load and inversely correlated with CD4(+) T cell counts. In antiretroviral therapy (ART)-naive volunteers, viral load and CD4(+) T cell count had stronger associations with CD8(+) and CD4(+) T cell activation, respectively. Virus suppression by ART was associated with a reduction in T cell activation, with a stronger observed effect on reducing CD8(+) compared with CD4(+) T cell activation. The presence of coinfection was associated with increased CD4(+) T cell activation but, interestingly, not with increased CD8(+) T cell activation. Our results suggest that distinct mechanisms differentially drive activation in CD4(+) and CD8(+) T cell subsets, which may impact the clinical prognostic values of T cell activation in HIV infection.
Eggena
Mark P
MP
University of California, San Francisco, California, USA. eggena@medicine.ucsf.edu
Barugahare
Banson
B
Okello
Martin
M
Mutyala
Steven
S
Jones
Norman
N
Ma
Yifei
Y
Kityo
Cissy
C
Mugyenyi
Peter
P
Cao
Huyen
H
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014454:Uganda; D019562:Viral Load
D044966:Anti-Retroviral Agents