# Brain Structural and Functional Connectome in HIV-associated Neuroinflammation

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2022 · $553,084

## Abstract

Abstract:
With an aging HIV population, it is becoming increasingly difficult to disentangle central nervous
system (CNS) injury due to HIV from that due to comorbidities such as vascular disease. A commonality between
HIV infection and aging is that both can be considered inflammatory conditions; thus HIV and aging can be
expected to have an additive, if not synergistic, negative effect on the CNS. The driver of CNS injury in HIV
infected individuals on combination antiretroviral therapy (cART) is likely multifactorial, and may include HIV viral
products, antiretrovirals CNS toxicity, traditional vascular risk factors and persistent CNS immune activation.
 Pro-inflammatory monocytes, such as those expressing tissue factor (TF+), are well-positioned to mediate
both inflammation and coagulopathy, thus likely to play a role in CNS injury. TF+ monocytes are increased in
HIV+ individuals, even in those on effective cART. Their ability to mediate both inflammation and coagulopathy
can lead to dysregulation of the CNS microcirculation, followed by ischemia, and then to demyelination. This
last effect is visible as white matter hyperintensities (WMH) in standard clinical MRI studies, for example FLAIR
sequence. More advanced pulse sequences, such as diffusion weighted imaging, can provide quantitative
measurements of abnormal white matter microstructure integrity even when there is no visible WMH on FLAIR.
 Well-treated HIV+ individuals are expected to have a very slow neurocognitive decline which is also reflected
in small, neuroimaging changes overtime. Therefore, it may take several years for those imaging changes
reflecting CNS injury to become quantifiable with standard methodology. We propose novel methodologies that
reproducibly construct structural and functional connectomes across subjects and between populations, thus
further improving our understanding in the evolution of HIV-associated CNS injury. These novel methods are
based on a rigorous statistical approach which will provide the reliability needed to ascertain small changes
overtime. We propose to implement these methodologies while investigating the role of TF+ monocytes, immune
cells at the crossroad of inflammation and coagulopathy, thus likely involved in HIV-associated CNS injury,
especially in an older population. The specific aims listed below will be investigated in a three-year longitudinal
cohort of 110 HIV+ participants and 110 HIV- age, gender and vascular risk factors matched controls. We have
chosen a cohort that is primarily composed of participants age ≥50 thus at greater risk of vascular disease.
 Aim 1. To assess via novel methodologies the longitudinal changes in the trajectory of brain structural
connectome and functional connectivity in HIV infected compared to HIV seronegative individuals in the context
of intermediaries of inflammation and coagulopathy (soluble CD14 and CD163, D-dimer, soluble tissue factor
and TF+ monocytes).
 Aim 2. To assess the mediation effec...

## Key facts

- **NIH application ID:** 10196934
- **Project number:** 5R01MH118020-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** GIOVANNI SCHIFITTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $553,084
- **Award type:** 5
- **Project period:** 2018-07-20 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196934

## Citation

> US National Institutes of Health, RePORTER application 10196934, Brain Structural and Functional Connectome in HIV-associated Neuroinflammation (5R01MH118020-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196934. Licensed CC0.

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