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.
B-cell phenotype and correlating factors were evaluated.
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.
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.
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.
aViral Evolution and Transmission Unit, Division of Immunology, Transplant and Infectious Diseases
bDepartment of Infectious and Tropical Diseases, San Raffaele Scientific Institute, Milan, Italy
cDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute
dDepartment of Infectious Diseases/Venhälsan, Stockholm South General Hospital, Stockholm, Sweden
eInfectious Diseases & Immunopathology Section, Department of Clinical Sciences, L. Sacco Hospital, University of Milan
fHuman Virology Unit, San Raffaele Scientific Institute, Milan, Italy.
*Francesca Chiodi and Gabriella Scarlatti contributed equally to the writing of the article.
Correspondence to Simone Pensieroso, PhD, Viral Evolution and Transmission Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. Tel: +39 02 2643 4910; fax: +39 02 2643 4905; e-mail: firstname.lastname@example.org
Received 7 August, 2012
Revised 21 December, 2012
Accepted 10 January, 2013
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