Status: Funded - Open
Does early cytomegalovirus infection contribute to immune defects in HIV-exposed, uninfected infants?
Christiana Smith, MD
BACKGROUND: HIV-exposed, uninfected (HEU) infants suffer from higher morbidity and mortality than their HIV-unexposed peers, mostly due to infectious causes. Multiple immune defects have been identified in HEU infants; the mechanism leading to these abnormalities is unknown.
GAP: Infants born to HIV-infected mothers are at high risk of acquiring Cytomegalovirus (CMV), a virus known to increase the susceptibility to secondary infections in immune compromised hosts. It is unknown whether CMV infection in early life contributes to the immune defects found in HEU infants.
HYPOTHESIS: Compared to CMV-uninfected HEU, CMV-infected HEU have higher rates of hospitalization and death. Cellular and humoral immune responses to infectious agents and vaccines are decreased in CMV-infected compared to CMV-uninfected HEU infants.
METHODS: In this case-control study, we will compare clinical and immunological outcomes between HEU infants who do or do not acquire CMV infection in early life. We will use stored data and blood samples from 227 Botswanan HEU infants who were originally recruited to an observational study of the effects of perinatal HIV and antiretroviral exposure on infant health and neurodevelopmental outcomes.
IMPACT: More than 1 million HEU infants were born in 2014, and this population is expected to continue to grow, as efforts to prevent mother-to-child transmission of HIV scale up. If our hypothesis is confirmed, the natural progression of this research would include clinical trials of antiviral medications to prevent or treat CMV infection in HIV-infected pregnant women and their infants; use of these drugs could result in improved immune development and better outcomes for millions of HEU infants.
University of Colorado Denver
United States, Botswana