#33: A Tale of Two Pneumos: the Impact of HIV Exposure or Infection Status on Pediatric Carriage of Streptococcus pneumoniae and Pneumocystis jirovecii, a Nested Case–control Analysis from the Pneumonia Etiology Research in Child Health (PERCH) study in Zambia

Background Most pediatric HIV cases in Africa reflect maternal to child transmission (MTCT). The persistently high seroprevalence of HIV in pregnant women (16.6%) and the low rates of mother to child HIV transmission (~2%) have resulted in a high number of children who are HIV exposed but uninfected (HEU). HIV exposed but uninfected (HEU) children have increased rates of morbidity and mortality vs. HIV unexposed and uninfected (HUU). Methods To explore the mechanisms behind this phenomenon, each case and control was sampled using a nasopharyngeal NP swab and an oropharyngeal (OP). A multiplex real-time polymerase chain reaction (PCR) assay was used to determine the presence of Streptococcus pneumoniae and Pneumocystis jirovecii in the NP/OP specimens. We compared nasopharyngeal carriage rates of S. pneumoniae and P. jirovecii between HIV-infected, HEU, or HUU case (pneumonia) and control (without pneumonia) children. In bivariate analyses, using carriage as a dichotomous outcome, proportions we compared using chi-square or odds ratios with 95% confidence intervals. In multivariate models, we created logistic and linear regression models adjusting for nutritional status as possible mediators of carriage status. Results SP carriage rates were similar between cases and controls. However, density was increased among HIV-infected children vs. HEU or HUU children (15.8 vs. 4.7 vs. 3.6 × 105 copies/mL, respectively). Among cases, PJ carriage among HIV positive, HEU and HUU children was 31%, 15% and 10%,, respectively, (P < 0.05) and carriage density was 63.9, 20.9, and 4.8 × 103 copies/mL, respectively (P < 0.05). In adjusted logistic regression models, HIV-infected cases were slightly more likely to be an S. pneumoniae carrier compared with HUU cases (aOR = 1.1; 95% CI: 0.57–2.14). In contrast, all other case/exposure combinations were less likely to be S. pneumoniae carriers with the lowest adjusted odds among HIV-infected controls children (aOR = 0.34; 95% CI: 0.17–0.71). The odds of being a PJ carrier was almost 6 times higher in HIV-infected cases than in HIV unexposed cases (aOR = 6.63; 95% CI: 3.24–13.54). Conclusions We demonstrate that HIV infection and HIV exposure without infection each have an impact on carriage rates and density for S. pneumoniae and P. jirovecii, though the magnitude and nature of these effects differs substantially between the two pathogens. This may be explained in part by differences in immune responses to these two different pathogens. Our analysis provides further evidence of fundamental differences in immune function among HIV exposed but uninfected infants compared with HIV unexposed, uninfected infants.