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Initiation of Antiretroviral Therapy Before Pregnancy Reduces the Risk of Infection-related Hospitalization in Human Immunodeficiency Virus–exposed Uninfected Infants Born in a High-income Country

Author(s)
Goetghebuer, Tessa; Smolen, Kinga K; Adler, Catherine; Das, Jishnu; McBride, Trevor; Smits, Gaby; Lecomte, Sandra; Haelterman, Edwige; Barlow, Patricia; Piedra, Pedro A; van der Klis, Fiona; Kollmann, Tobias R; Lauffenburger, Douglas A; Alter, Galit; Levy, Jack; Marchant, Arnaud; ... Show more Show less
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Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
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Abstract
Background Epidemiological studies conducted in low- and high-income countries showed that infants exposed to maternal human immunodeficiency virus (HIV) have a high risk of severe infections. Immune alterations during fetal life have been proposed as a possible mechanism. Methods This prospective study assessed the relative risk of hospitalization for infection in HIV-exposed uninfected (HEU) infants as compared to HIV-unexposed (HU) infants born in a high-income country (HIC). Markers of monocyte activation and levels of pathogen-specific antibodies were measured at birth to identify correlates of infant susceptibility. Results There were 27 of 132 HEU infants and 14 of 123 HU infants hospitalized for infection during the first year of life (adjusted hazard ratio [aHR] 2.33, 95% confidence interval [CI] 1.10-4.97). Most of this increased risk was associated with the time of initiation of maternal antiretroviral therapy (ART). As compared to HU infants, the risk of hospitalization for infection of HEU infants was 4-fold higher when mothers initiated ART during pregnancy (aHR 3.84, 95% CI 1.69-8.71) and was not significantly increased when ART was initiated before pregnancy (aHR 1.42, 95% CI 0.58-3.48). The activation of newborn monocytes and the reduced transfer of maternal antibodies were most intense following ART initiation during pregnancy, and predicted the risk of infant hospitalization. Conclusions These observations indicate that initiation of maternal ART before pregnancy reduces the susceptibility of HEU infants born in a HIC to severe infections, and that this effect could be related to the prevention of immune alterations during fetal life.
Date issued
2018-09
URI
https://hdl.handle.net/1721.1/125913
Department
Massachusetts Institute of Technology. Department of Biological Engineering
Journal
Clinical Infectious Diseases
Publisher
Oxford University Press (OUP)
Citation
Goetghebuer, Tessa et al. "Initiation of Antiretroviral Therapy Before Pregnancy Reduces the Risk of Infection-related Hospitalization in Human Immunodeficiency Virus–exposed Uninfected Infants Born in a High-income Country." Clinical Infectious Diseases 68, 7 (September 2018): 1193–1203 © 2018 The Author(s)
Version: Author's final manuscript
ISSN
1058-4838
1537-6591

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