While viral suppression can be achieved with combination antiretroviral therapy (cART), persons living with HIV (PLWH) remain at considerable risk of brain involvement and cognitive impairment. Despite evidence of vascular pathology in PLWH, these mechanisms are not well understood. This investigation will use new 4D Flow MRI capabilities to evaluate specific vascular mechanisms that may play a role in brain alterations and cognitive decline in suppressed PLWH (Aim 1). Neurovascular 4D flow MRI will be used to quantify total blood flow to the brain (TCBF) and to derive flow rates, peak velocities and the Pulsatility Index for the cerebral arteries (Aim 1). We will use Cardiac 4D Flow MRI to quantify ascending aortic flow, cardiac output/index and derive the aortic-carotid pulse wave velocity (PWV) ratio. This approach, which has not yet been used to evaluate virally suppressed PLWH, may provide new insights into vascular mechanisms. We are particularly interested in whether there are differences in the aortic-carotid PWV ratio and cerebral Pulsatility Index compared to age-matched seronegative controls  (Aim 1). We will enroll participants for our  hemodynamic analysis from a unique cohort with imaging and cognitive data available for early infection with well-documented cART initiation dates (PLWH and age-matched seronegative controls). By leveraging the archived data, this R21 funding can also accomplish a 10 year follow-up study to determine brain changes and cognitive decline over the first decade of infection in cART suppressed PLWH (Aim 2). We can determine whether the hypothesized vascular mechanisms are associated with the severity of cerebral small vessel disease (SVD), cortical thinning, localized volume loss and decline in specific cognitive functions in cART suppressed PLWH (Aim 3). If confirmed, these vascular mechanisms may inform new therapeutic strategies and these hemodynamic parameters may provide new measures of vascular risk and response to treatment in suppressed PLWH.

Primary contact: Susanne Schnell (PhD)
Investigators: Ann Ragin (PhD), TBD
Collaborations: Northwestern University (Ann Ragin)
Funding: NIH 1R21NS122511