Respiratory syncytial virus (RSV) and parainfluenza infections have been found to increase rates of hospitalization in the first year of life among HIV-exposed, HIV-uninfected infants, according to the results of a retrospective cohort study published in Clinical Infectious Diseases. These infants demonstrated robust antibody responses to vaccine antigens.

Using existing data from a group of HIV-exposed, uninfected (HEU) infants enrolled in previous trials between 2002 and 2013, investigators analyzed seroconversion to 6 respiratory viruses and antibody titers to 9 vaccine antigens using quantitative enzyme-linked immunosorbent assay (ELISA) or electrochemiluminescence. They included HEU infants whose 48-week serum samples were collected prior to their 12-month vaccinations. The investigators recruited a cohort of 12-month-old HIV-unexposed, uninfected (HUU) infants at well-child visits who had not yet received their 12-month vaccinations to serve as control group participants for the antibody concentration analysis.

The investigators looked for an association of seroconversion and antibody titers with hospitalization risk in the first year of life using multivariable modified Poisson regression models. They also used multivariable linear regression models to compare antibody levels between HEU infants and HUU infants from a single site.

Among 556 HEU infants included in the seroconversion analysis, 54{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} were boys, 55{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} were Black, 41{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} were Hispanic, and 17{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} were preterm. In the first year of life, 45.9{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} of these infants had seroconversion to at least one respiratory virus. There was no significant difference in the prevalence of hospitalization for respiratory viruses between infants who seroconverted to more than 1 virus and those who seroconverted to just 1 virus. The rate of hospitalization was 11.3{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} at a median age of 63 days (interquartile range [IQR], 20-153 days), with 37.8{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} for respiratory infections.

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HEU infants had a greater risk of all-cause hospitalization associated with seroconversion to RSV (adjusted risk ratio [aRR], 1.95; 95{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 1.21-3.15) and parainfluenza (aRR, 2.30; 95{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 1.42-3.73). HEU infants who seroconverted to RSV had a greater risk of hospitalization for respiratory infection (aRR, 2.50; 95{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 1.09-5.72). Per 1000 person-months, the incidence of RSV, parainfluenza, and influenza A or B viruses was 34.2 (95{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 30.4-38.4), 40.7 (95{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 37.1-44.7), 38.9 (9{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc}{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 35.0-43.2) and 28.6 (95{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} CI, 25.0-32.8), respectively. HEU infants who seroconverted to influenza A or B were not more likely to be hospitalized.

Among 525 HEU infants and 100 HUU infants included in the antibody analysis, 49{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} and 29{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} were Black, respectively; there were similar proportions of boys and Hispanic infants; and preterm birth occurred in 20{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} of HEU and 8{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} of HUU infants.

At 48 weeks, antibody concentrations to all vaccine antigens were higher in HEU infants than in HUU infants. However, there was no association between any antibody titers and hospitalization risk among HEU infants.

Limitations of the study included the inability to measure maternal and infant antibody concentrations at birth and lack of access to maternal vaccination data. Infants were enrolled over 11 years and may have been exposed to different viruses depending on their birth year, but investigators could not temporally associate hospitalizations for seroconversions with respiratory viruses.

“Our data suggest that HEU infants may benefit from prophylactic interventions to prevent RSV infection, including palivizumab or the long-acting monoclonal antibody nirsevimab,” the study authors wrote.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Smith C, Huo Y, Patel K, et al; Pediatric HIV/AIDS Cohort Study (PHACS) and IMPAACT P1025 study team. Immunologic and virologic factors associated with hospitalization in HIV-exposed, uninfected infants in the United States. Clin Infect Dis. Published online June 22, 2021. doi:10.1093/cid/ciab272

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