Immunologic and Virologic Factors Associated With Hospitalization in Human Immunodeficiency Virus-Exposed, Uninfected Infants in the United States

Christiana Smith, Yanling Huo, Kunjal Patel, Kirk Fetters, Shannon Hegemann, Sandra Burchett, Russell Van Dyke, Adriana Weinberg, Christiana Smith, Yanling Huo, Kunjal Patel, Kirk Fetters, Shannon Hegemann, Sandra Burchett, Russell Van Dyke, Adriana Weinberg

Abstract

Background: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience higher rates of morbidity and mortality than HIV-unexposed, uninfected (HUU) infants. Few studies have examined whether particular infections and/or immune responses are associated with hospitalization among HEU infants born in the United States.

Methods: We evaluated a subset of HEU infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 and/or Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for ART Toxicities studies. We determined seroconversion to 6 respiratory viruses and measured antibody concentrations to 9 vaccine antigens using quantitative ELISA or electrochemiluminescence. Multivariable modified Poisson regression models were fit to evaluate associations of seroconversion to each respiratory virus/family and antibody concentrations to vaccine antigens with risk of hospitalization in the first year of life. Antibody concentrations to vaccine antigens were compared between HEU infants and HUU infants from a single site using multivariable linear regression models.

Results: Among 556 HEU infants, seroconversion to respiratory syncytial virus (RSV) and parainfluenza was associated with hospitalization (adjusted risk ratio, 1.95 [95% CI, 1.21-3.15] and 2.30 [1.42-3.73], respectively). Antibody concentrations to tetanus toxoid, pertussis, and pneumococcal vaccine antigens were higher among 525 HEU compared with 100 HUU infants. No associations were observed between antibody concentrations with any vaccine and hospitalization among HEU infants.

Conclusions: RSV and parainfluenza contribute to hospitalization among HEU infants in the first year of life. HEU infants demonstrate robust antibody responses to vaccine antigens; therefore, humoral immune defects likely do not explain the increased susceptibility to infection observed in this population.

Keywords: HIV-exposed uninfected infants; antibodies; hospitalization; respiratory syncytial virus; vaccines.

© The Author(s) 2021. 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.
Flowchart of the HEU infant study population. Some infants were included in both the analysis of seroconversion to respiratory viruses and the analysis of vaccine titers if they met inclusion criteria for both analyses. Abbreviations: HEU, HIV-exposed, uninfected; HIV, human immunodeficiency virus; IMPAACT, International Maternal Pediatric Adolescent AIDS Clinical Trials Group; P1025, protocol 1025; PHACS SMARTT, Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for ART Toxicities.
Figure 2.
Figure 2.
Adjusted risk ratio of hospitalization comparing HEU infants with vs. without seroconversion to a specific respiratory virus. Each model adjusted for sex, race, ethnicity, preterm birth, low birth weight, mode of delivery, and maternal last CD4 count and viral load during pregnancy. aRR, adjusted risk ratio; CI, confidence interval; RSV, respiratory syncytial virus.

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