Background:  HIV infection is associated with increased susceptibility to invasive pneumococcal disease. Recent data in adults suggest that a persistent depletion of marginal zone memory (MZM) B cells occurs soon after HIV infection, and this depletion is not reversed by HAART. This loss correlates with reduced humoral immunity to pneumococcal polysaccharides, which may contribute to the persistent susceptibility to pneumococcal disease in HIV-infected patients. As B cell lineage development continues through childhood, we proposed to evaluate whether irreversible B cell lineage–specific depletion occurs in the pediatric HIV-infected population.

Methods:  Naïve (CD27^–), MZM (CD27⁺IgD⁺) and germinal center memory (CD27⁺IgD^–) B cell numbers were measured in whole blood from untreated HIV-infected children (n = 25), HAART-treated children (n = 76), and age-matched healthy controls (n = 42). These data were then correlated with B cell activation status (CD38 expression), HIV viral load, duration of disease (age), and CD4 count. Data were expressed as median and interquartile ranges. Comparisons between groups were performed using Wilcoxon tests. Multivariable analyses of factors associated with MZM B cell levels were performed using multiple linear regression.

Results:  HIV infection was associated with reduction in MZM B cells compared with age-matched controls (4.1% [2.3; 7.5] vs 7.1% [2.6; 10.6], p = 0.04). The reduction in MZM B cells was independent of age (p = 0.19) and was not reversed by HAART with or without virological control (3.1% [1.3; 5.5] and 4.5% [2.6; 7.6], respectively). In addition, there was an independent positive correlation between MZM B cell levels and HIV viral load (Spearman r = 0.22; p = 0.02). HIV viral load was associated with activation of all B cell subsets (p<0.005), however, multivariable analysis demonstrated a closer association between MZM B cells and HIV viral load (p = 0.06) than with B cell activation (p = 0.62). In contrast, naïve and germinal center memory B cell numbers were not different from the control population.

Conclusions:  Pediatric HIV infection is associated with irreversible depletion of MZM B cell numbers, despite control of viral load with HAART. The positive association between viral load, B cell activation status, and MZM numbers suggests that the MZM B cell population may be selectively targeted by HIV early in the course of infection, ultimately resulting in a permanent depletion of this lineage.