# Role of cerebral vasculature in brain ischemia in HIV infection

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $529,297

## Abstract

ABSTRACT
Cerebral small vessel disease (CSVD) and transient ischemic attacks (TIAs) are emerging
comorbidities of neuroHIV. The application is built on the most important findings from the
previous funding cycle and will evaluate the mechanistic events underlying the impact of HIV on
CSVD in relationship to TIA outcome and recovery (Aim 1) and HIV reactivation in the CNS and
its egress into the periphery (Aim 2). The significance of the proposed work drives primarily from
the facts that CSVD is the major cause of cognitive impairment, contributes to 25% of incidents
of brain ischemia, and more than doubles the risk of their recurrence. In addition, the risk of
developing transient ischemic attacks (TIAs) or other forms of brain ischemia is estimated to be
at least 1.5-2-fold higher in HIV-positive individuals compared to the control population. The
central hypothesis of the present proposal is that HIV-induced cerebral vascular pathology
drives neuroimmune activation, predisposing HIV-infected brains to the development of
CSVD and more severe TIA outcomes. Mechanistically, we will focus on the impact of HIV and
CSVD on reprogramming of mitochondria and the role of dysfunctional mitochondria in these
events. Our important preliminary data indicates that HIV can be reactivated from latently infected
HIV brains, and we show for the first time that this process also occurs as the result of brain
ischemia. We will further explore these processes, and will evaluate if reactivated HIV in the CNS
can egress into the periphery. The proposed research is highly innovative by its focus on novel
mechanisms underlying vascular comorbidities, such as CSVD and TIAs, in the HIV-infected
brain.
When completed, our application will provide critical insight into the role of HIV in CSVD and TIA
development. In addition, our research will provide important information about the reactivation
HIV from the brain and seeding into the periphery as the result of brain ischemia. The proposed
studies are innovative and are likely to identify novel opportunities for therapeutic intervention.

## Key facts

- **NIH application ID:** 10489292
- **Project number:** 5R01HL126559-06
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Michal Toborek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $529,297
- **Award type:** 5
- **Project period:** 2014-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489292

## Citation

> US National Institutes of Health, RePORTER application 10489292, Role of cerebral vasculature in brain ischemia in HIV infection (5R01HL126559-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10489292. Licensed CC0.

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