Immune and Metabolic Alterations in Children with Perinatal HIV Exposure

Abstract

With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed–and-uninfected (CHUU). Differences reported between these two groups include immune dysfunction and higher levels of inflammation, cognitive and metabolic abnormalities, as well as increased morbidity and mortality in CHEU. The reasons for these disparities remain largely unknown. The present review focuses on a proposed link between immunometabolic aberrations and clinical pathologies observed in the rapidly expanding CHEU population. By drawing attention, firstly, to the significance of the immune and metabolic alterations observed in these children, and secondly, the impact of their healthcare requirements, particularly in low- and middle-income countries, this review aims to sensitize healthcare workers and policymakers about the long-term risks of in utero exposure to HIV and ART.

Metabolic Alterations in Mothers Living with HIV and Their HIV-Exposed, Uninfected Infants

“…However, it remains unclear whether the inflammatory and metabolic derangements in PWLWH on ART and/or potential ART toxicity affect infant development in the millions Viruses 2024, 16, 313 2 of 14 of HEU infants born globally each year. Immunometabolic alterations could set infants on a path towards suboptimal growth, as well as a lifelong compromised immune function [5][6][7][8].…”

Reduced anti-viral IgG repertoire in HIV-exposed but uninfected infants compared to HIV-unexposed infants

“… 7 Multiple factors potentially explaining these observed health outcome disparities between iHUU and iHEU have been suggested, including long-term immunological differences which are possibly a result of in utero and postnatal immune activation, although the exact mechanism leading to these alterations is not clearly established. 8 , 9 Evidence of immunological differences in iHEU includes impaired T cell functionality characterized by a state of chronic activation and lower production of pro-inflammatory cytokines following stimulation with vaccine and polyclonal antigens. 10 , 11 , 12 , 13 Moreover, altered innate immune responses, such as lower expression of perforin and interferon-gamma (IFN-γ) in natural killer (NK) cells which are pivotal in controlling and fighting viral infections, have been reported.…”

Improving the prediction of the immune status state dynamics in children with HIV infection

“…К особен-ностям клиники и течения ВИЧ-И у детей, по сравнению с взрослыми пациентами, относится быстрое прогрессирование заболевания с ранним присоединением тяжелых оппортунистических инфекций, что [2,3]. Установлено, что развитие вторичных заболеваний (оппортунистических инфекций, злокачественных опухолей) у больных ВИЧ-И связано с формированием глубоких нарушений в иммунной системе [4,5]. Маркером выраженности иммуносупрессии у больных ВИЧ-И служит степень снижения количества основных клеток-мишеней для вируса -Т-хелперов (CD4-лимфоцитов) [6,7].…”