title: Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy.
abstract: OBJECTIVE
  Despite CD4(+) count restoration and viral load suppression with antiretroviral therapy (ART), HIV-infected children remain at increased risk of life-threatening infections including invasive pneumococcal disease (IPD). We therefore investigated whether persistent susceptibility to IPD following ART is associated with incomplete recovery of B-cell function.
  
  
  METHODS
  41 HIV-infected Malawian children commencing ART were followed-up for a 1 year period during which time blood samples were collected at 0, 3, 6 and 12 months for comprehensive immunophenotyping and pneumomococcal-specific Memory B-cell Enzyme-Linked Immunospot assays. In addition, nasopharyngeal swab samples were cultured to determine pneumococcal carriage rates.
  
  
  RESULTS
  Normalization of major lymphocyte subsets such as CD4(+) percentages was evident following 3 months of ART. The proportions of mature naïve B cells (CD19(+) CD10(-) CD27(-) CD21(hi)) and resting memory B cells (CD19(+) CD27(+) CD21(hi)) increased and apoptosis-prone mature activated B cells (CD19(+) CD21(lo) CD10(-)) decreased markedly by 12 months. However, in the context of high nasopharyngeal pneumococcal carriage rates (83%), restoration of pneumococcal protein antigen-specific B-cell memory was more delayed.
  
  
  CONCLUSIONS
  These data show that, in chronically HIV-infected children receiving ART, improvement in B-cell memory profiles and function is slower than CD4(+) T-cells. This supports early initiation of ART and informs research into optimal timing of immunization with pneumococcal vaccines.
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Oluwadamilola H
authors.initials: OH
authors.lastname: Iwajomo
authors.affiliation: Department of Pediatrics, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Peter
authors.initials: P
authors.lastname: Moons
authors.affiliation: Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Rose
authors.initials: R
authors.lastname: Nkhata
authors.affiliation: Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: David
authors.initials: D
authors.lastname: Mzinza
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, Australia.
authors.forename: Abiodun D
authors.initials: AD
authors.lastname: Ogunniyi
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom. Electronic address: adam.finn@bristol.ac.uk.
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008295:Malawi; D008297:Male; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D019562:Viral Load
keywords: Antiretroviral therapy; Children; ELISPOT; HIV; Malawi; Memory B cells; Pneumococcal infection