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Published on: January 12, 2016
Role of Brain Arterial Remodeling in HIV-Associated Cerebrovascular Outcomes
Antonio Spagnolo-Allende1, Jose Gutierrez1
1Department of Neurology, Columbia University Irving Medical Center, New York, NY, United States.
Insights
People living with HIV (PLWH) on combination antiretroviral therapy (cART) face increased risks of stroke and neurocognitive disorders due to brain arterial remodeling. Understanding these changes is key to reducing cerebrovascular disease in aging PLWH.
Area of Science:
- Neurology
- Immunology
- Cardiovascular Science
Background:
- Life expectancy for people living with HIV (PLWH) on combination antiretroviral therapy (cART) is increasing.
- This leads to a higher incidence of cerebrovascular disease and neurocognitive disorders in this population.
- Brain arterial remodeling is an emerging area of study for understanding HIV's impact on brain health.
Purpose of the Study:
- To review existing literature on HIV, cART, and their effects on brain arterial remodeling.
- To understand the relationship between HIV, arterial changes, cerebrovascular disease, and neurocognitive outcomes.
- To identify potential targets for reducing cerebrovascular disease in aging PLWH.
Main Methods:
- A comprehensive literature review was conducted.
- Databases searched included PubMed, EMBASE, Web of Science, and Wiley Online Library.
- Search terms focused on HIV, cART, brain, neuroimmunity, arterial remodeling, cerebrovascular disease, and neurocognitive disorders.
Main Results:
- PLWH on cART still experience higher risks of stroke and neurocognitive disorders than HIV-negative individuals.
- HIV vasculopathy and large artery atherosclerosis are distinct arterial remodeling patterns observed in PLWH.
- These arterial changes are linked to factors like immunosuppression, CD4 counts, and chronic inflammation, potentially contributing to neurocognitive deficits.
Conclusions:
- Cerebrovascular architecture is differentially affected by HIV in treated versus untreated individuals.
- Brain large artery atherosclerosis is common even with long-term immune reconstitution.
- Further research into HIV-associated arterial remodeling is needed to develop strategies for mitigating cerebrovascular risk in PLWH.
Abstract:
As the life expectancy of people living with HIV (PLWH) on combination antiretroviral therapy (cART) increases, so does morbidity from cerebrovascular disease and neurocognitive disorders. Brain arterial remodeling stands out as a novel investigational target to understand the role of HIV in cerebrovascular and neurocognitive outcomes. We therefore conducted a review of publications in PubMed, EMBASE, Web of Science and Wiley Online Library, from inception to April 2021. We included search terms such as HIV, cART, brain, neuroimmunity, arterial remodeling, cerebrovascular disease, and neurocognitive disorders. The literature shows that, in the post-cART era, PLWH continue to experience an increased risk of stroke and neurocognitive disorders (albeit milder forms) compared to uninfected populations. PLWH who are immunosuppressed have a higher proportion of hemorrhagic strokes and strokes caused by opportunistic infection and HIV vasculopathy, while PLWH on long-term cART have higher rates of ischemic strokes, compared to HIV-seronegative controls. Brain large artery atherosclerosis in PLWH is associated with lower CD4 nadir and higher CD4 count during the stroke event. HIV vasculopathy, a form of non-atherosclerotic outward remodeling, on the other hand, is associated with protracted immunosuppression. HIV vasculopathy was also linked to a thinner media layer and increased adventitial macrophages, suggestive of non-atherosclerotic degeneration of the brain arterial wall in the setting of chronic central nervous system inflammation. Cerebrovascular architecture seems to be differentially affected by HIV infection in successfully treated versus immunosuppressed PLWH. Brain large artery atherosclerosis is prevalent even with long-term immune reconstitution post-cART. HIV-associated changes in brain arterial walls may also relate to higher rates of HIV-associated neurocognitive disorders, although milder forms are more prevalent in the post-cART era. The underlying mechanisms of HIV-associated pathological arterial remodeling remain poorly understood, but a role has been proposed for chronic HIV-associated inflammation with increased burden on the vasculature. Neuroimaging may come to play a role in assessing brain arterial remodeling and stratifying cerebrovascular risk, but the data remains inconclusive. An improved understanding of the different phenotypes of brain arterial remodeling associated with HIV may reveal opportunities to reduce rates of cerebrovascular disease in the aging population of PLWH on cART.
