Epigenetic modifications and immune responses in HIV-infected infants: a narrative review

HIV infection in infants poses unique challenges due to the interplay between an immature immune system and the viral mechanisms that exploit it. Recent research has unveiled critical insights into how epigenetic modifications, such as DNA methylation, histone modifications, and noncoding RNA regulation, specifically influence immune responses in HIV-infected infants. These modifications are not merely passive markers of infection but active players in immune dysregulation, contributing to persistent immune activation and the skewing of T-cell differentiation. Emerging studies have highlighted that these epigenetic alterations may play a role in the heightened vulnerability of HIV-infected infants to opportunistic infections and their variable responses to antiretroviral therapy (ART). A growing body of evidence suggests that epigenetic changes in key immune regulatory genes are significantly different in HIV-infected infants compared to uninfected controls. These differences have been linked to altered expression of cytokines, impaired T-cell functionality, and chronic inflammation, which are pivotal in disease progression. Specifically, recent findings indicate that persistent DNA methylation changes in genes involved in T-cell exhaustion could be a major driver of the reduced efficacy of ART in some infants, potentially leading to long-term immune system impairment. Moreover, novel insights into how miRNAs modulate the immune environment in these infants suggest potential targets for therapeutic intervention, aiming to enhance immune recovery and reduce viral reservoirs.