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Accelerated Brain Aging and Cerebral Blood Flow Reduction in Persons With Human Immunodeficiency Virus
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Clinical Infectious Diseases 23 February 2021
Clinical Infectious Diseases 23 February 2021
Kalen J. Petersen,1 Nicholas Metcalf,1 Sarah Cooley,1 Dimitre Tomov,1 Florin Vaida,2 Robert Paul,3 and Beau M. Ances1
1Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA; 2Department of Family and Preventive Medicine, University of California, San Diego, California, USA; and 3Department of Psychology, University of Missouri, St Louis, Missouri, USA
While reduced CBF was specific to older PWH with DVL, accelerated structural aging was observed even in those with UVL. This may imply that structural aging results from a legacy effect of early tissue damage or is cART resistant. Our data are congruent with previous findings that PWH have reduced gray matter volume [4, 30–32] and diminished white matter integrity [5, 6]. Such degeneration, representing irreversible cell death, may explain why structural aging was independent of current VL.
In the current analysis, structural aging was associated with cognitive dysfunction. Cognitive impairment in PWH has previously been shown to be associated with reduced cortical thickness [32] and tissue volume loss [30]. We found that diminished psychomotor speed was linked with structural BAG, independent of disease status. Psychomotor function is often diminished in PWH [35] but improves with cART [36].
Taken together, our findings suggest that age-related effects in PWH are two-fold. Structural aging consists of physical alterations detectable by conventional MRI, including gray and white matter degeneration independent of VL. In contrast, CBF involves dynamic, VL-responsive changes at the vascular level, which may be mitigated by cART. Although cART itself is linked to neurological side effects [40], our observations suggest that HIV suppression preserves normal perfusion. In both CBF and volumetrics, HIV and aging interact to promote phenotypic changes, steepening the slope of pathology curves. However, these data do not rule out accentuation by comorbidities [2]. Future work with more extended longitudinal follow-up may determine whether neuroimaging measures are causally linked with successful viral suppression, or partly attributable to concurrent risk factors.

Persons with human immunodeficiency virus (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between human immunodeficiency virus (HIV) and aging. However, it remains unclear how brain aging varies with viral load (VL).
In this study, we compare magnetic resonance imaging (MRI) biomarkers among PWH with undetectable VL (UVL; ≤50 genomic copies/mL; n = 230), PWH with detectable VL (DVL; >50 copies/mL; n = 93), and HIV-uninfected (HIV–) controls (n = 206). To quantify gray matter cerebral blood flow (CBF), we utilized arterial spin labeling. To measure structural aging, we used a publicly available deep learning algorithm to estimate brain age from T1-weighted MRI. Cognitive performance was measured using a neuropsychological battery covering 5 domains.
Associations between age and CBF varied with VL. Older PWH with DVL had reduced CBF vs PWH with UVL (P = .02). Structurally predicted brain aging was accelerated in PWH vs HIV– controls regardless of VL (P < .001).
Overall, PWH had impaired learning, executive function, psychomotor speed, and language compared to HIV– controls. Structural brain aging was associated with reduced psychomotor speed (P < .001).

Brain aging in HIV is multifaceted. CBF depends on age and current VL and is improved by medication adherence. By contrast, structural aging is an indicator of cognitive function and reflects serostatus rather than current VL.

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