Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy

•HIV-infected children on ART have delayed recovery of pneumococcal B-cell memory.•Pneumococcal carriage remained high during ART.•Mature naïve and resting memory B cells increased after 3 months of ART.•Apoptosis prone B cell proportions reduced during ART to levels seen in controls.

SummaryObjectiveDespite 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.Methods41 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.ResultsNormalization 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− CD21hi) and resting memory B cells (CD19+ CD27+ CD21hi) increased and apoptosis-prone mature activated B cells (CD19+ CD21lo 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.ConclusionsThese 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.