Background. Persons with HIV (PWH) undergo white matter changes, which can be quantified using the brain-age gap (BAG), the difference between chronological age and neuroimaging-based brain-predicted age. Accumulation of microstructural damage may be accelerated in PWH, especially with detectable viral load (VL). Methods. In total, 290 PWH (85% with undetectable VL) and 165 HIV-negative controls participated in neuroimaging and cognitive testing. BAG was measured using a Gaussian process regression model trained to predict age from diffusion magnetic resonance imaging in publicly available normative controls. To test for accelerated aging, BAG was modeled as an age × VL interaction. The relationship between BAG and global neuropsychological performance was examined. Other potential predictors of pathological aging were investigated in an exploratory analysis. Results. Age and detectable VL had a significant interactive effect: PWH with detectable VL accumulated +1.5 years BAG/ decade versus HIV-negative controls (P = .018). PWH with undetectable VL accumulated +0.86 years BAG/decade, although this did not reach statistical significance (P = .052). BAG was associated with poorer global cognition only in PWH with detectable VL (P, .001). Exploratory analysis identified Framingham cardiovascular risk as an additional predictor of pathological aging (P = .027). Conclusions. Aging with detectable HIV and cardiovascular disease may lead to white matter pathology and contribute to cognitive impairment.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalJournal of Infectious Diseases
Issue number1
StatePublished - Jul 1 2022


  • HIV
  • MRI
  • aging
  • brain age
  • diffusion tensor imaging
  • machine learning
  • white matter


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