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

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.

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.