Maternal HIV infection and antiretroviral exposure in fetuses and newborns: Unintended consequences following successful prevention of vertical HIV transmission

Globally, more than one million children who are HIV-exposed but uninfected (CHEU) are born every year. Numerous studies have documented that CHEU are at increased risk for preterm delivery, infectious morbidity, immune cell abnormalities, impaired growth, neurodevelopmental delay, and death. However, the underlying mechanisms of these adverse health outcomes are poorly characterized. Investigators have hypothesized that inflammation in the absence of effective HIV viral suppression in the mother, antenatally, viral coinfections during gestation, or exposure to specific antiretroviral medications, may lead to altered immune cell development, and longitudinal growth or neurodevelopmental delays in the growing fetus and infant, but no specific factors have been clearly identified. This paucity of knowledge has hampered opportunities for early effective interventions. The WHO recommends all pregnant women living with HIV receive immediate lifelong antiretroviral therapy (ART). Scale-up of ART has reduced vertical transmission of HIV dramatically. This commendable global effort has resulted in rapidly expanding numbers of CHEU. There are approximately 15 million CHEU globally. However, the welcome news of far fewer infants acquiring HIV infection in utero, intrapartum, or through breastfeeding, has been tempered by consistent reports documenting adverse outcomes in CHEU. Cohort studies from as far back as 2006 across diverse settings including France, multiple countries in sub-Saharan Africa, and India, have documented higher rates of infectious morbidity and mortality, impaired psychomotor development, and reduced growth velocity in CHEU. Additional perinatal risk factors from intrauterine ARV and HIV exposure, include associations for preterm birth, and lower birthweight or small-for-gestational age. In this Research Topic, we invite investigators to publish manuscripts that address why CHEU have these poor clinical outcomes. Areas of interest include but are not limited to:• Identifying associations between specific ARVs including long-acting injectable formulations and timing of their administration in pregnancy with teratogenic effects preterm birth, low birthweight, and small-for-gestational age.• lmproved understanding of immune phenotypic alterations at the maternal–fetal interface, in the placenta, cord, and neonatal blood, and whether such changes contribute to increased risk of infectious morbidity and mortality.• Characterization and comparison of vaccine responses to childhood immunizations in CHEU.• Genomic changes identified in blood and tissue that may account for the clinical differences observed in CHEU versus infants and children that are non-exposed. Topic editors: Rana Chakraborty, Gabriella Scarlatti Source: https://www.frontiersin.org/research-topics/78464/maternal-hiv-infection-and-antiretroviral-exposure-in-fetuses-and-newborns-unintended-consequences-following-successful-prevention-of-vertical-hiv-transmission