An Augmented Aging Process in Brain White Matter in HIV

T. Kuhn; T. Kaufmann; N.T. Doan; L.T. Westlye; J. Jones; R.A. Nunez; S.Y. Bookheimer; E.J. Singer; C.H. Hinkin; A.D. Thames

The mechanisms by which HIV and age result in augmented neurodegeneration are unclear. Holt and colleagues 6 suggest two potential explanations regarding the relationship between HIV infection and increased brain aging. First, the increased brain age (BAG) may be explained by premature WM aging resulting from the virus facilitating neurodegenerative processes 35 , such as axonal injury, loss of axonal density, reduced patency of axons. Alternatively, advanced age may increase the effects of the virus on the CNS, thereby creating a synergistic interaction effect between HIV and aging 6 . Our finding that lifetime highest HIV RNA viral load, particularly in the context of advanced chronological age, was related to augmented WM aging (i.e. BAG) supports the first hypothesis. In line with this hypothesis, HIV effects on the brain have been shown to occur via similar cellular mechanisms as normal aging 36 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/265199 doi: bioRxiv preprint volume 9 . Similar to that reported by Cole et al., we did not find significant relationships between WM BAG and Nadir CD4 or HIV duration. Our findings expand upon these previous results by providing data suggesting the mechanism through which this augmented aging process deleteriously affects WM microstructure. Our results also further the literature in that we found a significant relationship between BAG and peak HIV RNA viral load as well as a significant age*peak viral load interactive effect on BAG, indicating that the effects of disease burden on brain integrity are more pronounced with advanced age.