Research
Gut microbiota and immunity in infants exposed to HIV
Infants exposed to HIV but not infected (iHEU), display heightened immune activation, inflammation and have high infectious morbidity compared to those who are HIV unexposed (iHU). The mechanisms behind these phenomena are not well understood. We are evaluating if there is a causal relationship between early life gut microbiota in iHEU and these clinical outcomes. We perform clinical research using samples obtained from human cohorts and conduct follow up reverse translational studies using preclinical models to gain mechanistic insights. Our goal is to unravel mechanisms that underlie poor health outcomes in iHEU which will guide development of microbiota-targeted interventions to improve health outcomes in these infants.
Gut microbiota and inflammatory biomarkers in neonates who are HIV-exposed but uninfected (nHEU) compared to those who are HIV-unexposed (nHU). (A) Differentially abundant gut bacteria between nHU and nHEU. (B) Plasma concentration of CRP.
Project 1:
We are testing the hypothesis that the gut microbiota early in life in iHEU causes elevated inflammation and impairs immunity to enteric pathogens using murine models.
Project 2:
iHEU are exposed to HIV and combined antiretroviral medication in utero and during breast feeding. Also, mothers living with HIV have an increased likelihood of cytomegalovirus (CMV) reactivation which may lead to congenital or early CMV infection in iHEU. In resource-limited settings, these factors independently or synergistically contribute to the poor health outcomes observed in infants exposed to HIV. While combined antiretroviral therapy is effective in suppressing viral replication, these medication may have unintended secondary effects, highlighting the need for further follow-up research. We are investigating the impact of maternal combined antiretroviral therapy on the enteric microbiota and inflammatory responses in offspring.