Synergistic effects of high early-life stress exposure and HIV infection on reaction time variability

Abstract

Addressing comorbidities contributing to cognitive impairment in people living with HIV (PLWH) remains imperative. Prior studies utilizing reaction time intra-individual variability (RT-IIV), a robust behavioral marker of cognitive dysfunction, demonstrate increased cognitive impairment in adults living with HIV who have high early life stress (ELS) exposure relative to those with low-ELS exposure. Yet, it is unknown whether RT-IIV elevations are due to high-ELS alone or both HIV-status and high-ELS. In the current study, we explore the potential additive effects of HIV and high-ELS exposure on RT-IIV to better characterize the independent and combined effects of these factors on RT-IIV among PLWH. We assessed 59 PLWH and 69 HIV-negative healthy control (HC) participants with either low or high ELS on RT-IIV during a working memory task (1-back). We observed a significant interaction between HIV status and ELS exposure on RT-IIV, PLWH who had experienced high ELS demonstrating RT-IIV elevations relative to all other groups. In addition, RT-IIV was significantly associated with ELS exposure in PLWH, but not in the HC group. We also observed associations between RT-IIV and measures of HIV-disease severity (plasma HIV viral load, nadir CD4) among PLWH. Taken as a whole, these findings provide novel evidence of the combined effects of HIV and high-ELS exposure on RT-IIV, and thus suggest HIV-related and ELS-related neural abnormalities may act in an additive or synergistic manner to affect cognition. Such data warrant further investigation into the neurobiological mechanisms associated with HIV and high-ELS exposure that contribute to increased neurocognitive dysfunction among PLWH.

Keywords: HIV; adverse childhood experiences; childhood trauma; early life stress; reaction time variability.