Antiretroviral Therapy Restores Age-Dependent Loss of Resting Memory B Cells in Young HIV-Infected Zambian Children

Rainwater-Lovett, Kaitlin PhD, MPH*; Nkamba, Hope C. MPH; Mubiana-Mbewe, Mwnagelwa MBChB; Moore, Carolyn B. MBBCh, MSc‡,§; Margolick, Joseph B. MD, PhD; Moss, William J. MD, MPH*,‖

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000074
Basic and Translational Science
Abstract

Background: Antiretroviral therapy (ART) is associated with incomplete restoration of resting memory B (RMB) cell percentages in adults infected with HIV, but the effects on RMB cells in children are less well defined, in part because changes in RMB cell percentages are confounded by the development and maturation of the RMB cell pool. The objective of this study was to assess the effect of age at ART initiation on RMB cell percentages over time in HIV-infected Zambian children.

Methods: RMB cell percentages (CD19+CD21+CD27+) were measured by flow cytometry in 146 HIV-infected Zambian children (9–120 months old) at baseline and at 3-month intervals after ART initiation and in 34 control children at a single study visit.

Results: RMB cell percentages among untreated HIV-infected children younger than 24 months did not differ from those of control children (P = 0.97). Among HIV-infected children older than 24 months of age, however, each 12-month increase in age at ART initiation was associated with a 1.8% decrease in RMB cell percentage. In contrast, RMB cell percentages in control children up to 48 months increased 4.4% with each 12-month increase in age. After 12 months of ART, children aged 24–60 months had a significant increase in RMB cell percentages that no longer differed from those of control children.

Conclusions: Initiation of ART in 2- to 5-year-old HIV-infected children resulted in reconstitution of RMB cell percentages to levels similar to control children and may help restore normal development and maintenance of B-cell immunity.

Author Information

*Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

Virology Laboratory, University Teaching Hospital, Lusaka, Zambia;

Center for Infectious Disease Research-Zambia, Lusaka, Zambia;

§Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Alabama, AL; and

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Dr Rainwater-Lovett is now with the Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD; Carolyn B. Moore is now with Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC).

Correspondence to: William J. Moss, MD, MPH, 615 N. Wolfe Street, Room E6547, Baltimore, MD (e-mail: wmoss@jhsph.edu).

Presented at the Keystone Symposium “Immunological Mechanisms of Vaccination”, October 27 to November 1, 2010, Seattle, WA.

This study was funded by the U.S. National Institute of Allergy and Infectious Diseases at the National Institutes of Health (R01AI070018).

The authors have no conflicts of interest to disclose.

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Received November 14, 2013

Accepted November 14, 2013

© 2014 by Lippincott Williams & Wilkins