HIV and ART in children

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Background

The use of antiretroviral therapy (ART) during pregnancy is now standard care to prevent mother-to-child HIV transmission. The population of HIV-exposed uninfected (HEU) children is expanding rapidly, and over one million HEU infants are born each year globally. First HEU are nowadays reaching adulthood. Several recent studies have reported that HEU children, particularly in low- and middle-income countries, are at risk of poor outcomes, including increased inflammation, impaired growth and neurodevelopment issues. However, results are controversial in the literature, and the underlying mechanistic pathways remain unclear.



Although the benefits of ART during pregnancy are out of the question, there is concern regarding the potential long-term effects of intrauterine ART exposure on the fetus. A direct pathogenic effect of both HIV (via inflammation /chronic inflammation / microbial translocation) and ART (mitochondrial dysfunction, ROS and other metabolic pathways) is feasible. However, social determinants of health might be also contributing to increasing health risks in this population, commonly exposed to poverty, nutritional deficits, and limited access to health care.



In the era of universal ART, the question of whether intrauterine HIV and ART exposure leads to long-term consequences needs to be further addressed. Are there microbiome-related changes in HEU children? Is there chronic inflammation a real concern in this population? Can we expect growth delays in the absence of nutritional deficits and social adversity? Is there any ART regimen preferred if so? Are there long-term neurocognitive problems to be aware of? And if so, can social determinants of health be acting as confounders? Are there reasons to expect publication bias in this area of research? A better understanding of the underlying pathways and confounders is crucial to inform future prevention and to design intervention strategies.

Keywords: HIV, human immunodeficiency virus, ART, antiretroviral therapy, mother-to-child HIV transmission, HIV-exposed uninfected (HEU) children, HEU, intrauterine exposure, pregnancy, fetus

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