Summary 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. Highlights • 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.
【저자키워드】 HIV, children, memory B cells, Malawi, Antiretroviral therapy, ELISPOT, pneumococcal infection,