HIV increases sleep-based brain age despite antiretroviral therapy

Study Objectives Age-related comorbidities and immune activation raise concern for advanced brain aging in people living with HIV (PLWH). The brain age index (BAI) is a machine learning model that quantifies deviations in brain activity during sleep relative to healthy individuals of the same age. High BAI was previously found to be associated with neurological, psychiatric, cardiometabolic diseases, and reduced life expectancy among people without HIV. Here, we estimated the effect of HIV infection on BAI by comparing PLWH and HIV− controls. Methods Clinical data and sleep EEGs from 43 PLWH on antiretroviral therapy (HIV+) and 3,155 controls (HIV−) were collected from Massachusetts General Hospital. The effect of HIV infection on BAI, and on individual EEG features, was estimated using causal inference. Results The average effect of HIV on BAI was estimated to be +3.35 years (p < 0.01, 95% CI = [0.67, 5.92]) using doubly robust estimation. Compared to HIV− controls, HIV+ participants exhibited a reduction in delta band power during deep sleep and rapid eye movement sleep. Conclusion We provide causal evidence that HIV contributes to advanced brain aging reflected in sleep EEG. A better understanding is greatly needed of potential therapeutic targets to mitigate the effect of HIV on brain health, potentially including sleep disorders and cardiovascular disease