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

Autor: Evans C; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe. ceri.evans@qmul.ac.uk.; Blizard Institute, Queen Mary University of London, London, UK. ceri.evans@qmul.ac.uk., Mutasa K; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Rukobo S; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Govha M; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Mushayanembwa P; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Chasekwa B; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Majo FD; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Tavengwa NV; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Broad J; Blizard Institute, Queen Mary University of London, London, UK., Noble C; Blizard Institute, Queen Mary University of London, London, UK., Gough EK; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Kelly P; Blizard Institute, Queen Mary University of London, London, UK.; Tropical Gastroenterology & Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia., Bourke CD; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; Blizard Institute, Queen Mary University of London, London, UK., Humphrey JH; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Ntozini R; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Prendergast AJ; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; Blizard Institute, Queen Mary University of London, London, UK.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 17; Vol. 15 (1), pp. 2909. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1038/s41467-023-44166-2
Abstrakt: 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 10 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 10 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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