Although a switch from short-lived apoptosis prone B cells to longer-lived naïve and resting memory B cells was seen relatively early after initiation of ART, there were no significant changes observed in the

percentages and absolute numbers of total CD19+ B cells during ART in this cohort during the 12 months of observation. Some previous studies in children have shown no changes selleck chemicals llc in total CD19+ B cells during ART37 while other studies in both adults and children have shown rises.18, 38, 39 and 40 There are numerous factors that may differ between these samples which could have contributed to these discordant findings but the most immediate apparent need is to follow these trends over a longer observation period. We have previously demonstrated acquisition of pneumococcal protein-specific T cell and B cell immunity in both low carriage and high carriage populations.10, 41, 42, 43,

44 and 45 This naturally acquired immunity may occur as a result of multiple immunizing carriage events to a range of pneumococcal proteins expressed at the mucosal surface.46 In African children, pneumococcal nasopharyngeal carriage occurs very early in life and reaches very high rates47 and, as in this study, carriage rates may be higher among those with HIV infection.48 In this context, we have recently shown that even in minimally symptomatic HIV-infected children, pneumococcal protein antigen-specific memory B-cell numbers are low compared with HIV-uninfected children.10 The delayed recovery in pneumococcal antigen Sunitinib specific B cell memory after institution of ART that we describe here may indicate that these HIV-infected children remain both more vulnerable to invasive pneumococcal disease and to prolonged or higher density carriage. Understanding more clearly how B cell immune reconstitution relates to pneumococcal colonization will be important in countries such as Malawi

with high HIV prevalence and where Thiamine-diphosphate kinase pneumococcal conjugate vaccine (PCV) has recently been introduced into the routine infant immunization schedule, particularly since the effectiveness of these vaccines is to a great extent mediated by effects on carriage and transmission.49 Many of the children reported here were commenced on ART with a low percentage CD4 nadir (Fig. 1A). It is possible that the delayed and incomplete restoration of antigen-specific B cell function we observed would have been ameliorated by earlier initiation of ART.18, 50 and 51 This question has begun to be tackled programmatically as the thresholds for initiating ART are lowered but merits further investigation if vaccines are to be targeted effectively. This work was supported by the Joan Franklin-Adams Trust (scholarship to O.H.I), David Baum Memorial Appeal (grant to A.F and R.S.H.), MLW Core Programme Grant from the Wellcome Trust (funding to R.S.H. – grant number 084679/Z/08/Z) and a Wellcome Trust project grant (funding to R.S.H.