B-cell subset alterations and correlated factors in HIV-1 infection.
OBJECTIVE
During HIV-1 infection, the development, phenotype, and functionality of B cells are impaired. Transitional B cells and aberrant B-cell populations arise in blood, whereas a declined percentage of resting memory B cells is detected. Our study aimed at pinpointing the demographic, immunological, and viral factors driving these pathological findings, and the role of antiretroviral therapy in reverting these alterations.


METHODS
B-cell phenotype and correlating factors were evaluated.


METHODS
Variations in B-cell subsets were evaluated by flow cytometry in HIV-1-infected individuals naive to therapy, elite controllers, and patients treated with antiretroviral drugs (virological control or failure). Multivariable analysis was performed to identify variables independently associated with the B-cell alterations.


RESULTS
Significant differences were observed among patients' groups in relation to all B-cell subsets. Resting memory B cells were preserved in patients naive to therapy and elite controllers, but reduced in treated patients. Individuals naive to therapy and experiencing multidrug failure, as well as elite controllers, had significantly higher levels of activated memory B cells compared to healthy controls. In the multivariate analysis, plasma viral load and nadir CD4 T cells independently correlated with major B-cell alterations. Coinfection with hepatitis C but not hepatitis B virus also showed an impact on specific B-cell subsets. Successful protracted antiretroviral treatment led to normalization of all B-cell subsets with exception of resting memory B cells.


CONCLUSIONS
Our results indicate that viremia and nadir CD4 T cells are important prognostic markers of B-cell perturbations and provide evidence that resting memory B-cell depletion during chronic infection is not reverted upon successful antiretroviral therapy.
Viral Evolution and Transmission Unit, Division of Immunology, Transplant and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. pensieroso.simone@hsr.it
Simone
S
Pensieroso
Laura
L
Galli
Silvia
S
Nozza
Nicolas
N
Ruffin
Antonella
A
Castagna
Giuseppe
G
Tambussi
Bo
B
Hejdeman
Donatella
D
Misciagna
Agostino
A
Riva
Mauro
M
Malnati
Francesca
F
Chiodi
Gabriella
G
Scarlatti
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000998:Antiviral Agents / Q000627:therapeutic use; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060085:Coinfection; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology*
D000998:Antiviral Agents