Rates of Hospitalization and Infection-Related Hospitalization Among Human Immunodeficiency Virus (HIV)-Exposed Uninfected Children Compared to HIV-Unexposed Uninfected Children in the United States, 2007-2016

Sarah M Labuda, Yanling Huo, Deborah Kacanek, Kunjal Patel, Krista Huybrechts, Jennifer Jao, Christiana Smith, Sonia Hernandez-Diaz, Gwendolyn Scott, Sandra Burchett, Fatima Kakkar, Ellen G Chadwick, Russell B Van Dyke, Pediatric HIV/AIDS Cohort Study, Ellen Chadwick, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Shearer, Mary Paul, Chivon McMullen-Jackson, Ruth Eser-Jose, Lynnette Harris, Murli Purswani, Mahoobullah Mirza Baig, Alma Villegas, Lisa Gaye-Robinson, Jawara Dia Cooley, James Blood, Patricia Garvie, William Borkowsky, Sandra Deygoo, Jennifer Lewis, Arry Dieudonne, Linda Bettica, Juliette Johnson, Karen Surowiec, Katherine Knapp, Jill Utech, Megan Wilkins, Jamie Russell-Bell, Nicolas Rosario, Lourdes Angeli-Nieves, Vivian Olivera, Stephan Kohlhoff, Ava Dennie, Jean Kaye, Russell Van Dyke, Karen Craig, Patricia Sirois, Cecelia Hutto, Paige Hickman, Dan Marullo, Stephen A Spector, Veronica Figueroa, Megan Loughran, Sharon Nichols, Elizabeth McFarland, Emily Barr, Christine Kwon, Carrie Glenny, Mobeen Rathore, Kristi Stowers, Saniyyah Mahmoudi, Nizar Maraqa, Rosita Almira, Karen Hayani, Lourdes Richardson, Renee Smith, Alina Miller, Gwendolyn Scott, Maria Mogollon, Gabriel Fernandez, Anai Cuadra, Toni Frederick, Mariam Davtyan, Jennifer Vinas, Guadalupe Morales-Avendano, Zoe M Rodriguez, Lizmarie Torres, Nydia Scalley, Sarah M Labuda, Yanling Huo, Deborah Kacanek, Kunjal Patel, Krista Huybrechts, Jennifer Jao, Christiana Smith, Sonia Hernandez-Diaz, Gwendolyn Scott, Sandra Burchett, Fatima Kakkar, Ellen G Chadwick, Russell B Van Dyke, Pediatric HIV/AIDS Cohort Study, Ellen Chadwick, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Shearer, Mary Paul, Chivon McMullen-Jackson, Ruth Eser-Jose, Lynnette Harris, Murli Purswani, Mahoobullah Mirza Baig, Alma Villegas, Lisa Gaye-Robinson, Jawara Dia Cooley, James Blood, Patricia Garvie, William Borkowsky, Sandra Deygoo, Jennifer Lewis, Arry Dieudonne, Linda Bettica, Juliette Johnson, Karen Surowiec, Katherine Knapp, Jill Utech, Megan Wilkins, Jamie Russell-Bell, Nicolas Rosario, Lourdes Angeli-Nieves, Vivian Olivera, Stephan Kohlhoff, Ava Dennie, Jean Kaye, Russell Van Dyke, Karen Craig, Patricia Sirois, Cecelia Hutto, Paige Hickman, Dan Marullo, Stephen A Spector, Veronica Figueroa, Megan Loughran, Sharon Nichols, Elizabeth McFarland, Emily Barr, Christine Kwon, Carrie Glenny, Mobeen Rathore, Kristi Stowers, Saniyyah Mahmoudi, Nizar Maraqa, Rosita Almira, Karen Hayani, Lourdes Richardson, Renee Smith, Alina Miller, Gwendolyn Scott, Maria Mogollon, Gabriel Fernandez, Anai Cuadra, Toni Frederick, Mariam Davtyan, Jennifer Vinas, Guadalupe Morales-Avendano, Zoe M Rodriguez, Lizmarie Torres, Nydia Scalley

Abstract

Background: Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)-exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of child hospitalization.

Methods: HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006-2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization.

Results: A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization.

Conclusions: Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Keywords: HEU; HIV; immunology; pediatrics.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Adjusted associations of maternal human immunodeficiency virus (HIV) disease characteristics with the risk of inpatient admission in the first 2 years of life among HIV-exposed uninfected infants in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study Dynamic Cohort (N = 2404). Incidence rates and ratios were obtained from a Poisson regression model with robust variance. Separate multivariable models were fit for each exposure adjusting for sex, race/ethnicity, maternal age at delivery, maternal education, household income, tobacco/alcohol use during pregnancy, receipt of vaccination during pregnancy, maternal infections during pregnancy, and region of research site. Participants without any in utero antiretroviral (ARV) exposure (n = 25) were excluded from the model building for maternal ARV exposure. Participants with unknown mode of maternal HIV acquisition (n = 251) were excluded from the model building for this exposure. Inpatient admissions for diagnoses made within 7 days of full-term life were not considered as incident events. Abbreviations: ARV, antiretroviral; cART, antiretroviral regimen containing at least 3 drugs from at least 2 classes; CI, confidence interval; HIV, human immunodeficiency virus; INSTI, integrase inhibitor; PI, protease inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor.

References

    1. Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS data 2018. Available at: . Accessed 12 November 2018.
    1. Shapiro RL, Lockman S. Mortality among HIV‐exposed infants: the first and final frontier. Clin Infect Dis 2010; 50:445–7.
    1. Brennan AT, Bonawitz R, Gill CJ, et al. . A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children. AIDS 2016; 30:2351–60.
    1. Ruck C, Reikie BA, Marchant A, Kollmann TR, Kakkar F. Linking susceptibility to infectious diseases to immune system abnormalities among HIV-exposed uninfected infants. Front Immunol 2016; 7:1–12.
    1. Slogrove AL, Goetghebuer T, Cotton MF, Singer J, Bettinger JA. Pattern of infectious morbidity in HIV-exposed uninfected infants and children. Front Immunol 2016; 7:1–8.
    1. Brahmbhatt H, Kigozi G, Wabwire-Mangen F, et al. . Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr 2006; 41:504–8.
    1. Marinda E, Humphrey JH, Iliff PJ, et al. . Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J 2007; 26:519–26.
    1. Slogrove A, Reikie B, Naidoo S, et al. . HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life. J Trop Pediatr 2012; 58:505–8.
    1. Evans C, Jones CE, Prendergast AJ. HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination. Lancet Infect Dis 2016; 16:e92–e107.
    1. Thorne C, Newell M, Dunn D. Hospitalization of children born to human immunodeficiency virus-infected women in Europe. Pediatr Infect Dis J 1997; 16:1151–6.
    1. Paul ME, Chantry CJ, Read JS, et al. . Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women: The women and infants transmission study. J Pediatric Infect Dis Soc 2005; 24:45–56.
    1. Wizman S, Lamarre V, Valois S, Soudeyns H, Lapointe M, Kakkar F. Health outcomes among HIV exposed uninfected infants in Québec, Canada. In: MOPEB2017, Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, Canada. 19-22 July 2015.
    1. Mussi-Pinhata MM, Freimanis L, Yamamoto AY, et al. . National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study Group Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Latin American and Caribbean countries: the National Institute of Child Health and Human Development International site development initiative perinatal study. Pediatrics 2007; 119:e694–704.
    1. Adler C, Haelterman E, Barlow P, Marchant A, Levy J, Goetghebuer T. Severe infections in HIV-exposed uninfected infants born in a European country. PLoS One 2015; 10:e0135375.
    1. Powis KM, Slogrove AL, Okorafor I, et al. . Maternal perinatal HIV infection is associated with increased infectious morbidity in HIV-exposed uninfected infants. Pediatr Infect Dis J 2018; 1.
    1. Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR. The PHACS SMARTT study: assessment of the safety of in utero exposure to antiretroviral drugs. 2016; 7:199.
    1. US Centers for Medicare and Medicaid Services. MAX general information.2018. Available at: . Accessed 10 January 2019.
    1. von Gottberg A, Wolter N, Tempia S, et al. . Epidemiology of acute lower respiratory tract infection in HIV-exposed uninfected infants. Pediatrics 2016; 137. doi:10.1542/peds.2015-3272.
    1. Wester C, Moffat C, Thior I, et al. . The aetiology of diarrhoea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding. Paediatr Int Child Health 2015; 36:189–97.
    1. Rollins NC, Ndirangu J, Bland RM, Coutsoudis A, Coovadia HM, Newell ML. Exclusive breastfeeding, diarrhoeal morbidity and all-cause mortality in infants of HIV-infected and HIV uninfected mothers: an intervention cohort study in KwaZulu Natal, South Africa. PLoS One 2013; 8:1–10.
    1. US Department of Health and Human Services. Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States Available at: . Accessed 27 January 2019.
    1. Reikie BA, Adams RCM, Leligdowicz A, et al. . Altered innate immune development in HIV-exposed uninfected infants. J Acquir Immune Defic Syndr 2014; 66:245–55.
    1. Smith C, Jalbert E, de Almeida V, et al. . Altered natural killer cell function in HIV-exposed uninfected infants. Front Immunol 2017; 8:470.
    1. Rich KC, Siegel JN, Jennings C, Rydman RJ, Landay AL. Function and phenotype of immature CD4+ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers. Clin Diagn Lab Immunol 1997; 4:358–61.
    1. Ono E, Nunes dos Santos AM, de Menezes Succi RC, et al. . Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART. Braz J Med Biol Res 2008; 41:700–8.
    1. Clerici M, Saresella M, Colombo F, et al. . T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV. Blood 2000; 96:3866–71.
    1. Huo Y, Patel K, Scott GB, et al. . Lymphocyte subsets in HIV-exposed uninfected infants and HIV-unexposed uninfected infants. J Allergy Clin Immunol 2017; 140:605–8.e3.
    1. Gupta A, Mathad JS, Yang WT, et al. . Maternal pneumococcal capsular IgG antibodies and transplacental transfer are low in South Asian HIV-infected mother-infant pairs. Vaccine 2014; 32:1466–72.
    1. Dzanibe S, Adrian PV, Mlacha SZK, Dangor Z, Kwatra G, Madhi SA. Reduced transplacental transfer of group B Streptococcus surface protein antibodies in HIV-infected mother-newborn dyads. J Infect Dis 2017; 215:415–9.
    1. Srinivasjois R, Slimings C, Einarsdóttir K, Burgner D, Leonard H. Association of gestational age at birth with reasons for subsequent hospitalisation: 18 years of follow-up in a Western Australian population study. PLoS One 2015; 10:1–11.
    1. Kuhn L, Kasonde P, Sinkala M, et al. . Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants? Clin Infect Dis 2006; 41:1654–61.
    1. Mussi-Pinhata MM, Motta F, Freimanis-Hance L, et al. . NISDI Perinatal Study Group Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants. Int J Infect Dis 2010; 14(Suppl 3):e176–82.
    1. Taron-Brocard C, Le Chenadec J, Faye A, et al. . France REcherche Nord&Sud Sida-HIV Hepatites-Enquete Perinatale Francaise-CO1/CO11 Study Group Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis 2014; 59:1332–45.
    1. National Center for Health Statistics. Data finder—health, United States, 2017. Available at: . Accessed 27 January 2019.

Source: PubMed

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