# Adaptation and Implementation of Clinical Practice Guidelines to Improve Stroke Outcomes in Zambia

> **NIH NIH K01** · JOHNS HOPKINS UNIVERSITY · 2022 · $139,861

## Abstract

PROJECT SUMMARY
Stroke is the second leading cause of death and leading cause of disability worldwide, and people with HIV
(PWH) are at more than double the risk of stroke compared to HIV-uninfected (HIV-) individuals. Sub-Saharan
Africa (SSA) shoulders the greatest burden of stroke and, because it’s also home to ~2/3 of the global
population of PWH, HIV likely substantially contributes to this burden. However, the mechanisms leading to
excess stroke risk amongst PWH are not well-understood and, therefore, optimal ways to prevent stroke
amongst PWH are not established. We hypothesize that vitamin D deficiency (VDD) may be involved in the
etiopathogenesis of stroke in PWH. VDD is more common in PWH than HIV- populations, can be exacerbated
by antiretroviral therapy (ART), and is highly prevalent in SSA. There is conflicting evidence about whether
VDD predisposes to stroke in HIV- populations. However, because both HIV infection and VDD lead to
endothelial dysfunction which may then result in stroke, we hypothesize that VDD and HIV infection
synergistically interact to increase the risk of stroke among PWH.
In this proposal, we seek to demonstrate that VDD is a mechanistic link between HIV infection, endothelial
dysfunction, and ischemic stroke in SSA. We will leverage developing neurology clinical and research capacity
in Zambia in collaboration with more senior investigators from the United States to rigorously test this
hypothesis. In order to do this, we will conduct a case-control study at the University Teaching Hospital (UTH)
in Lusaka, Zambia consisting of (1) cases: ART-treated PWH with ischemic strokes; and (2) controls: ART-
treated PWH without stroke. Participants will undergo clinical and demographic assessments, and blood will
be collected for determination of 25-hydroxyvitamin D level and biomarkers of endothelial dysfunction,
including intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and C reactive protein.
If VDD is associated with stroke in PWH, this research will provide the preliminary data necessary for a
subsequent large-scale, multinational clinical trial of vitamin D supplementation for primary stroke prevention in
PWH. If successful, vitamin D may offer a relatively inexpensive and scalable intervention to prevent strokes in
PWH across the world, an increasing concern especially amongst ART-treated people aging with HIV.

## Key facts

- **NIH application ID:** 10613703
- **Project number:** 3K01TW011771-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DEANNA Rae Saylor
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $139,861
- **Award type:** 3
- **Project period:** 2021-09-22 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10613703

## Citation

> US National Institutes of Health, RePORTER application 10613703, Adaptation and Implementation of Clinical Practice Guidelines to Improve Stroke Outcomes in Zambia (3K01TW011771-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10613703. Licensed CC0.

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