Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants

• DOI: 10.1038/s41467-023-44166-2
• Publication Date: 2024-04-17T10:01:58Z
• Authors: Ceri Evans; Kuda Mutasa; Sandra Rukobo; Margaret Govha; Patience Mushayan...; Bernard Chasekwa; Florence D. Majo; Naume V. Tavengwa; Jonathan Broad; Christie Noble; Ethan K. Gough; Paul Kelly; Claire D. Bourke; Jean H. Humphrey; Robert Ntozini; Andrew J. Prender...
• Keywords: Viremia; Cytomegalovirus

Abstract Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure maternal viraemia, dysfunction, and co-infections during pregnancy. In a secondary analysis SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, factors shaping development infants. Maternal inflammation cytomegalovirus viraemia were independently associated with deaths: doubled for each log 10 rise C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33–3.27), 1.6-fold viral load (aHR 1.62; 1.11–2.36). girls, was more strongly than cytomegalovirus; boys, protein. At age one month, infants had distinct milieu, characterised by raised soluble CD14 an altered CD8 + T-cell compartment. Alterations immunophenotype systemic generally greater boys girls. Collectively, these findings show how pregnancy environment women HIV underlies their offspring sex-differentiated manner, highlights potential new intervention strategies transform outcomes children. ClinicalTrials.gov/NCT01824940.