Meet the CIPHER grantees
||The Children’s Hospital of Philadelphia
||Coleen Cunningham, Duke University
Matthew Kelly is an Assistant Professor of Paediatrics in the Division of Infectious Diseases at Duke University. His CIPHER research studied the immunological or microbiological basis for the poor pneumonia outcomes of HIV-exposed, uninfected (HEU) infants. His current research is investigating the impact of the upper respiratory microbiome on the risk of pneumonia during infancy.
More information on Matthew | Email
“Funding from the CIPHER grant programme enabled me to generate preliminary data to inform successful grant applications and create a valuable specimen repository, and prepared me to transition to an independent researcher and faculty member.”
Research project: The effect of in utero exposure to HIV and antiretroviral therapy on the microbiology and outcomes of severe pneumonia
Despite the absence of HIV infection, HEU infants have increased infectious morbidity and mortality. Although multiple factors may contribute to this, immune abnormalities resulting from in utero exposure to HIV and ART are one hypothesized mechanism. HEU infants have fewer CD4+ cells and lower neutrophil counts, and acquire lower levels of maternal antibodies to several common childhood pathogens.
The CIPHER project
Dr Kelly focused on the health outcomes of HEU infants with pneumonia, the leading killer of children worldwide, and respiratory syncytial virus (RSV), the most common cause of pneumonia among infants. He conducted a prospective cohort study of children aged one to 23 months with pneumonia and a cross-sectional study of healthy neonates and their mothers. The primary aims of these studies were to:
- Determine if HEU infants with pneumonia are at higher risk of treatment failure compared with HIV-unexposed infants, and to determine whether in utero exposure to combination antiretroviral therapy (ART) is associated with treatment failure among HEU infants.
- Evaluate if in utero exposure to HIV and ART is associated with lower levels of RSV antibody among healthy newborns, and explore if this results from reduced placental transfer of antibody.
The premise was that an improved understanding of the causes and outcomes of pneumonia among HEU infants might inform prevention or treatment strategies that reduce mortality among these vulnerable children.
This research demonstrated that HEU infants have higher pneumonia-related mortality than HIV-unexposed infants, and that reduced breastfeeding mediates nearly half of this association. In addition, Dr Kelly found that HIV exposure is associated with reduced placental transfer of RSV antibody to infants, suggesting that HEU infants are at higher risk of severe RSV disease and should be prioritized for future RSV preventative strategies.
A respiratory virus panel was validated at the National Health Laboratory in Gaborone, improving Botswana’s ability to monitor local viral activity and respond to viral pandemics. The project also built local capacity through mentorship of four paediatric residents and funding to support a University of Botswana Masters student who used specimens collected from study participants for her laboratory-based thesis project. During the funding period, Dr Kelly was awarded two additional grants to continue his Botswana-based research into the health outcomes of HEU children.