Epigenetic Effects of HIV and Childhood Maltreatment in Women

Introduction: People with HIV have disproportionately higher rates of adverse childhood experiences compared to the general population. This, in turn, is linked to long-term physical and mental health consequences. DNA methylation - a heritable, reasonably stable and quantifiable epigenetic mechanism implicated in gene silencing - may offer a useful lens that helps understand how HIV and childhood trauma become biologically embedded and affect disease risk profiles. Methods: This study aimed to identify regional and network level methylomic signatures associated with HIV and childhood maltreatment scores in South African women who bear the highest dual burden. DNA methylation profiling using the Illumina Infinium EPIC V2 kit was performed on DNA extracted from blood samples of 238 women with or without HIV with varying levels of childhood maltreatment. Regional DNA methylation analyses, composed of correlation tests on specific CpG sites and on genetic regions, were conducted for each of HIV and childhood maltreatment scores. Thereafter, a weighted gene Co-Expression Network Analysis (WGCNA) was conducted on HIV and childhood maltreatment scores to determine co-expression modules associated with the variable of interest. Finally, causal mediation analysis of the most significant network module was conducted to clarify the direction of association. Results: Neither HIV status nor childhood maltreatment was associated with DNA methylation at site-specific or regional levels. Network methylation effects were, however, observed, with three out of four network modules that were differentially methylated in HIV, implicating genes involved in immune pathways. One network module, composed of an abundance of genes relating to neurotransmitter functioning, was associated with childhood maltreatment. Both causal analyses implied that HIV and childhood maltreatment preceded the epigenetic effects. Conclusions: The findings suggest that DNA methylation in immune pathways may partially explain the immune and neurologic effects of HIV. The link between childhood maltreatment and neuronal processes warrants further investigation.