Persistent Vascular Dysfunction and Cognition among Virally Suppressed People with HIV

About This Grant

Modified Project Summary/Abstract Section The widespread access to antiretroviral therapy (ART) has converted HIV infection into a chronic and manageable condition. To date, PWH who have stable access to ART mostly maintain stable HIV suppression and achieve a more comparable life expectancy as people without HIV (PWoH), constituting an aging population of PWH. However, PWH continue to incur residual effects of persistent immune and metabolic dysfunction, resulting in a higher risk of developing non-communicable diseases (NCDs) when compared to PWoH. Among NCDs, cardiovascular disease (CVD) and neurocognitive impairment (NCI) are not only contributing factors to morbidity and mortality but also two of the most disabling conditions that compromise perceived ratings of life satisfaction. In PWoH, extensive research has established vascular disease as a key contributor to cognitive decline and NCI. Vascular brain injury (VBI) is a crucial risk factor for cognitive decline in all forms of dementia. Considering the persistently elevated risk of CVD in PWH despite suppressive ART, there is a compelling rationale that CVD and VBI are accentuated in older PWH. Notably, our understanding between CVD risks, vascular dysfunction, and cognitive outcomes in older PWH on ART is essentially derived from studies from high-income countries (HICs), with effectively no empirical evidence regarding complex interplay between persistence of inflammation and vascular dysfunction in older PWH residing in low- to middle-income countries (LMICs). Research findings from the global north cannot be extrapolated into LMICs given the significant differences in HIV subtype, as well as the unique genetic and environmental risks on vascular dysfunction. Moreover, cognitive studies in Asia have been limited by the use of screening measures for cognitive impairment, as well as by an inadequate focus on older PWH on stable ART. This R21 proposal leverages the robust HIV research infrastructure of the HIV Netherlands Australia Thailand Research Collaboration (HIVNAT) of the Thai Red Cross AIDS Research Centre (TRCARC) in Bangkok, Thailand. We will enrol older PWH, along with age- and sex-matched PWoH. Participants will undergo blood sampling for immune activation and vascular dysfunction biomarker measurement, optical coherence tomography angiography (OCTA) and comprehensive cognitive assessment. Through a biological-structural cognitive framework, this proposed study aims to address the aforementioned knowledge gaps by examining the potential link between persistent inflammation, vascular dysfunction, and cognitive performance in older PWH on stable ART in LMICs. In addition to providing potential mechanistic insight and intervention targets to NCI in older PWH, this proposed work will enhance research capacity building at HIVNAT to support future studies aimed at deeper phenotyping of cognitive outcomes and discovery of risk determinants, including modifiable factors that can be targeted in future studies.