No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project

Abstract

Background Despite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology. Methods We performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models. Results 123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels. At baseline, PLWH had poorer global cognitive performance (P<0.01), lower grey matter volume (P=0.04), higher white matter hyperintensity load (P=0.02), abnormal white-matter microstructure (P<0.005) and greater ‘brain-predicted age difference’ (P=0.01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P>0.1). Cognitive performance was stable across the study period in both groups. Conclusions Our finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls.