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
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 s...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press (OUP)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125913 |
| _version_ | 1811093497171673088 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 |
| author_sort | Goetghebuer, Tessa |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:45:27Z |
| format | Article |
| id | mit-1721.1/125913 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:45:27Z |
| publishDate | 2020 |
| publisher | Oxford University Press (OUP) |
| record_format | dspace |
| spelling | mit-1721.1/1259132022-10-02T03:55:34Z 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 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 Massachusetts Institute of Technology. Department of Biological Engineering 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. 2020-06-22T15:49:34Z 2020-06-22T15:49:34Z 2018-09 2017-11 2020-06-19T13:25:52Z Article http://purl.org/eprint/type/JournalArticle 1058-4838 1537-6591 https://hdl.handle.net/1721.1/125913 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) en http://dx.doi.org/10.1093/cid/ciy673 Clinical Infectious Diseases Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Oxford University Press (OUP) Prof. Lauffenberger via Howard Silver |
| spellingShingle | 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 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://hdl.handle.net/1721.1/125913 |
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