Epstein-Barr virus load and immune activation in human immunodeficiency virus type 1-infected patients.
BACKGROUND
Patients infected with HIV-1 are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. Chronic immune activation is a hallmark of HIV-1 pathogenesis and may play a role in B-cell stimulation and expansion of EBV-infected cells.


OBJECTIVE
The aim of the study was to define the relationship between parameters of immune activation and EBV load in HIV-1-infected subjects.


METHODS
A total of 156 HIV-1-infected patients were studied. EBV types 1 and 2 were quantified on peripheral blood mononuclear cells by multiplex real-time PCR. Plasma levels of cytokines and lipopolysaccharide (LPS) were determined by immunoenzymatic assays. B-cell activation was analyzed by flow cytometry.


RESULTS
EBV-DNA was detected in 114 patients, and in all but 3 was EBV type 1. The median [interquartile] EBV-DNA load was 43[1-151] copies/10(5) PBMC. EBV-DNA load was higher in patients with detectable HIV-1 plasma viremia, despite good immunological status (CD4>500 cells/μl), than in patients with undetectable HIV-1 plasma viremia regardless of immunological status (46[5-136] copies/10(5) cells vs 17[1-56] copies/10(5) cells, p=0.008). Patients with high EBV-DNA load (>median value) had higher levels of LPS and proinflammatory cytokines (IL-6, IL-10 and TNF-α) than patients with low EBV load. Furthermore, percentages of activated B-cells correlated with EBV-DNA load (r(s)=0.754; p<0.001).


CONCLUSIONS
Overall, these findings indicate a strong association between HIV-1 viremia, markers of immune activation and EBV load and suggest that persistence of HIV-1 viremia and immune activation, regardless of peripheral CD4 cell depletion/repopulation, may favor expansion of EBV-infected cells and onset of EBV-related malignancies.
Department of Oncology and Surgical Sciences, Section of Oncology, AIDS Reference Centre, University of Padova, Italy.
Maria Raffaella
MR
Petrara
Anna Maria
AM
Cattelan
Marisa
M
Zanchetta
Lolita
L
Sasset
Riccardo
R
Freguja
Ketty
K
Gianesin
Maria Grazia
MG
Cecchetto
Francesco
F
Carmona
Anita
A
De Rossi
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D016207:Cytokines; D004279:DNA, Viral; D012367:RNA, Viral