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


Evans, Ceri ORCID: 0000-0001-9122-9748, Mutasa, Kuda, Rukobo, Sandra, Govha, Margaret, Mushayanembwa, Patience, Chasekwa, Bernard, Majo, Florence D, Tavengwa, Naume V, Broad, Jonathan, Noble, Christie et al (show 6 more authors) (2024) Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants. Nature communications, 15 (1). p. 2909.

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

Item Type: Article
Uncontrolled Keywords: Humans, Cytomegalovirus, Pregnancy Complications, Infectious, Viremia, Cytomegalovirus Infections, HIV Infections, Inflammation, C-Reactive Protein, Pregnancy, Child, Infant, Female, Male
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 30 Apr 2024 08:24
Last Modified: 30 Apr 2024 08:24
DOI: 10.1038/s41467-023-44166-2
Open Access URL: https://doi.org/10.1038/s41467-023-44166-2
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3180658
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