Researchers probe HIV-associated stroke in Zambia
March/ April 2023 | Volume 22 Number 2
Photo courtesy of Deanna SaylorDr. Deanna Saylor (left) teaches a group of trainee doctors while visiting a patient at University Teaching Hospital in Lusaka, Zambia. Her project seeks to develop new care systems for stroke in Zambia.
Sub-Saharan Africa shoulders the greatest burden of stroke, which is the leading cause of disability worldwide and the second leading cause of death. The region’s high incidence of stroke is at least partially linked to the two-thirds of the world’s population with HIV residing there. Compared to uninfected individuals, people with HIV (PWH) have more than double the risk of stroke, both ischemic stroke—when blood supply to the brain is interrupted or reduced, preventing cerebral tissues from getting oxygen and nutrients—and hemorrhagic stroke—when a blood vessel bursts in the brain.
A team led by Dr. Deanna Saylor at University Teaching Hospital (UTH) in Lusaka, Zambia, are exploring the entwined issues of stroke and HIV. Because the mechanisms leading to excess stroke risk among PWH are poorly understood, the best ways to prevent stroke among these patients have not yet been established. Yet it is data from HIV-uninfected populations that guides primary stroke prevention, acute treatment, and secondary stroke prevention in people with HIV, even though “stroke is very different in people with HIV,” said Saylor.
Features of HIV-associated stroke
“In Zambia, the HIV rate is around 12%, which is pretty high, so we tend to see a lot of patients with HIV presenting with stroke,” said Dr. Stanley Zimba, lead author of a 2021 study, “Risk factors and outcomes of HIV-associated stroke in Zambia.” The study (co-authored by Saylor) retrospectively reviewed charts of all adults admitted to UTH with a diagnosis of stroke between October 2018 and March 2019. The researchers, who wanted “to get a better understanding and to generate data that would be helpful in terms of managing patients,” discovered that participants with HIV were younger than uninfected participants, said Zimba. “The mean age at stroke presentation was 48 for PWH compared to 61 for uninfected patients, so there’s a big disparity there.” PWH also tended to lack traditional stroke risk factors, such as hypertension and diabetes; a full third of PWH participants had no other identified risk factor than HIV. Another finding: Deep vein thrombosis was more common during hospitalization amongst PWH though no in-hospital mortality differences were seen when compared to HIV-negative patients.
These findings will help the team develop new strategies for preventing stroke in people with HIV, said Zimba. “Early antiplatelet therapy or use of other medications like statins might be needed to lower stroke risk in this population.” Additional factors that complicate prevention and rehabilitation, including whether patients are taking antiretroviral therapy (ART), how long they have been on ART, and the presence of opportunistic infections, will also need to be considered. “PWH may have different needs from those of the general population when it comes to rehabilitation, especially nutritional rehabilitation, and also physical therapy, especially when malnutrition and opportunistic infections are in the background,” stated Zimba. PWH likely require more extensive primary care evaluations, while policy adjustments to address their needs might be necessary in high-risk settings.
Overall, Zimba is confident his work will benefit not only Zambia but the globe. “Stroke risk factors, primary prevention, treatment, and rehabilitation in PWH are all very important and cut across various clinical practices—yet none of these features are governed by borders. Stroke can occur anywhere in the world where there is a patient with HIV,” he said.
Exploring possible mechanisms underlying HIV-associated stroke
Saylor’s Fogarty-funded project,
Adaptation and Implementation of Clinical Practice Guidelines to Improve Stroke Outcomes in Zambia, seeks to generate new knowledge and help develop new care systems for stroke in Zambia. “Our main focus is to use an evidence-based approach to implementation science in order to adapt stroke guidelines from high-resourced settings to Zambia and to develop a stroke treatment protocol that is applicable in low-resource settings and improves patient outcomes,” she told Fogarty in an email.
While stroke looks different in PWH, “whether the strokes themselves are different is a bit less clear,” said Saylor, an associate professor of neurology at Johns Hopkins Medicine. Some initial studies suggested HIV-associated strokes were more likely to be large vessel strokes—where blood blockage occurs in one of the main arteries—with poorer outcomes. Yet participants in these studies often had poorly controlled HIV (as it was early in the epidemic), and opportunistic infections had caused their strokes. In contemporary studies, most HIV-associated stroke is unrelated to opportunistic infections, Saylor said. “Recent work from Botswana found that people with HIV were more likely to have small vessel strokes with better outcomes. Our own work from Zambia showed no differences in stroke type or in-hospital mortality between people with and without HIV.”
Yet stroke occurring at younger ages in PWH who lack traditional risk factors still suggests “alternative mechanistic pathways for HIV-associated stroke,” she said.
Saylor has long been interested in the role of vitamin D in neurological disorders. Vitamin D, a nutrient our bodies need to absorb calcium, has numerous interactions with the immune system, noted Saylor, a neuroimmunologist by training. She is conducting a complementary project examining whether vitamin D deficiency (VDD) might be involved in the cause and development of stroke in PWH.
Among people who are being treated for HIV with ART, this vitamin deficiency is common, while other medications more frequently used in Zambia, including older seizure drugs such as phenobarbital and phenytoin, and rifampin for the treatment of TB, may also cause VDD. Linking this vitamin shortfall with HIV-associated stroke is based on mounting studies, added Saylor. “Vitamin D deficiency may play a role in the development of multiple sclerosis (MS) and also leads to more active disease in those with MS. It has also been implicated in a variety of other neurological disorders, including Parkinson's disease and amyotrophic lateral sclerosis.”
Saylor postulates that VDD may increase the risk of stroke by leading to endothelial dysfunction. In stroke, vitamin D plays a role in the stabilization and function of vascular endothelial cells, which line the interior surface of blood vessels. Another possibility: VDD worsens a patient’s chronic inflammatory state (due to HIV), and this may lead to an increased risk of stroke. “If our hypothesis is correct and VDD does play a role in stroke risk in people with HIV, this could lead to changes in how we approach stroke prevention and treatment for these patients,” said Saylor.
Updated April 7, 2023
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