13, 14, 15, 16 and 17 Moir and colleagues have reported that despite adequate CD4+ count recovery with ART, chronically infected adults have poor B cell memory functional profiles in response to HIV and non-HIV antigens when compared to individuals receiving ART with more recent infection. 18 We therefore hypothesized that the persistent susceptibility to IPD seen in African children receiving ART may be explained by poor recovery of B-cell function and consequent Natural Product Library nmr delay in the re-establishment of

natural immunity to S. pneumoniae. Accordingly we prospectively investigated children with vertically acquired HIV infection commencing ART in Malawi where there is a high burden of IPD.19 We demonstrate that normalization of the circulating B cell phenotype occurs rapidly following the initiation of ART but that, in the context of high nasopharyngeal pneumococcal carriage rates, reconstitution of pneumococcal protein antigen-specific B cell memory is slower. Following written informed consent from parents or guardians, 45 HIV-infected children eligible to commence ART according to the Malawi National ART program guidelines operating at the

time of enrollment, based either on clinical criteria (WHO pediatric stage 3 or 4) or on low CD4+ count or percentage20 were recruited at Queen Elizabeth Central Hospital (Blantyre, Malawi), a large district and tertiary Forskolin solubility dmso referral hospital. A maximum of 5 ml whole blood and a nasopharyngeal swab sample were collected from each study participant on enrollment. In order to exclude malaria as a confounding factor in the immunological assays, all children were tested for malaria by microscopic examination of blood films. Children were monitored for a 1 year period following commencement of ART, during which time blood samples were collected at 0, 3, 6 and 12 months, while nasopharyngeal swab samples were collected monthly for the first 6 months, and then

every 2 months thereafter. None of the participants received any pneumococcal vaccine before or during the study. C59 This study complies with relevant guidelines and institutional practices of the Malawi-Liverpool Wellcome Trust Clinical Research Programme and the University of Malawi College of Medicine and was approved by the College of Medicine Research Ethics Committee (P.11/07/591). Thirty-seven HIV-uninfected controls within the same age range undergoing elective surgery at the same hospital were recruited as part of a separate contemporaneous study reported elsewhere.10 The median values for pneumococcal carriage and major phenotypic parameters, from these children were used for comparative purposes.