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Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy

Afran, Louise; Jambo, Kondwani C; Nedi, Wilfred; Miles, David JC; Kiran, Anmol; Banda, Dominic H; Kamg'ona, Ralph; ... Heyderman, Robert S; + view all (2022) Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy. The Journal of Infectious Diseases 10.1093/infdis/jiac133. (In press). Green open access

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Abstract

BACKGROUND: HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa, highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated if HIV-exposure dysregulates HEU immunity, vaccine-antibody production and human herpes virus (HHV) amplify this effect. METHODS: 34 HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort, followed up to 6 weeks of age; and 43 HIV-infected and 61 HIV-uninfected mother-infant pairs into a longitudinal infant cohort, at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HU infants. RESULTS: We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HU infants. HHV infection was similar between HEU and HU infants. CONCLUSION: In the era of antiretroviral therapy (ART)-mediated viral suppression, HIV-exposure may dysregulate monocyte and B cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

Type: Article
Title: Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/infdis/jiac133
Publisher version: https://doi.org/10.1093/infdis/jiac133
Language: English
Additional information: © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America and HIV Medicine Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: CMV, EBV, HIV-exposure, adaptive immunity, infants, innate immunity, neonates, vaccines
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10147150
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