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 ORCID: https://orcid.org/0000-0002-3195-2210, Nedi, Wilfred, Miles, David J C, Kiran, Anmol, Banda, Dominic H, Kamg’ona, Ralph, Tembo, Dumizulu, Pachnio, Annette, Nastouli, Eleni, Ferne, Brigit, Mwandumba, Henry ORCID: https://orcid.org/0000-0003-4470-3608, Moss, Paul, Goldblatt, David, Rowland-Jones, Sarah, Finn, Adam and Heyderman, Robert S (2022) 'Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy'. Journal of Infectious Disease, Vol 226, Issue 7, pp. 1243-1255.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Enzymes > QU 135 Enzymes QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WS Pediatrics > By Age Groups > WS 430 Infancy
Faculty: Department:	Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.1093/infdis/jiac133
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	16 Aug 2022 13:25
Last Modified:	14 Jun 2023 11:34
URI:	https://archive.lstmed.ac.uk/id/eprint/20293

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