# Impact of Treatment on Brain Integrity in the Earliest Stages of HIV Infection

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-ST. LOUIS · 2021 · $587,255

## Abstract

ABSTRACT
This study addresses a critical gap in the field of HIV neuropathogenesis. Previous investigations of brain integrity
during the earliest stages of infection describe two opposing neuroimaging signatures of disease. The
inconsistency likely reflects the challenges inherent in conducting this work in the US given the limited access to
treatment-naïve individuals in early disease stages (Fiebig I-V). Leveraging a highly unique cohort of acutely
infected individuals (AHI) in Thailand, our preliminary data reveals intact brain structure and function in treatment-
naïve individuals infected for less than two weeks. However, after two years of suppressive combination
antiretroviral therapy (cART) initiated within weeks of infection, neuroimaging abnormalities develop in the context
of suppressive cART. Further, the degree of brain impairment corresponds to increased levels of monocytes
expressing receptors involved in CNS migration and CSF levels of neuronal dysfunction. In this study we will
answer the critical question of whether cART is sufficient to halt the detrimental impact of HIV on the brain when
initiated within weeks of infection, or whether the brain abnormalities observed in our preliminary analyses progress
beyond expectations for HIV- controls despite otherwise successful treatment. This study will overcome limitations
in the existing literature because all participants in this study will start cART within days of viral exposure. This work
is timely and builds on funded studies that will substantially leverage costs of data acquisition. We will examine
longitudinal multimodal imaging outcomes (resting state fMRI, diffusion tensor imaging, and structural volumetrics)
of AHI (n=60) as well as enrollment and data capture from demographically-similar individuals with chronic HIV
infection (CHI; n=40) and HIV- controls (n=40). A mixed model design will determine if individuals with AHI develop
brain injury similar to CHI despite suppressive cART and identify key mechanistic predictors to the evolution of
brain abnormalities. Confirmation of our preliminary data demonstrating progressive brain abnormalities despite
initiation of cART during the earliest possible period of infection would provide a strong argument that treatment
administered under ideal clinical circumstances does not prevent the onset of brain abnormalities. Additionally,
evidence of persistent neural injury despite cART instituted during AHI would identify key mechanisms of HIV
neuropathogenesis and potential high-impact targets for clinical interventions.

## Key facts

- **NIH application ID:** 10201435
- **Project number:** 5R01MH113560-05
- **Recipient organization:** UNIVERSITY OF MISSOURI-ST. LOUIS
- **Principal Investigator:** Robert Harris Paul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $587,255
- **Award type:** 5
- **Project period:** 2017-08-25 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201435

## Citation

> US National Institutes of Health, RePORTER application 10201435, Impact of Treatment on Brain Integrity in the Earliest Stages of HIV Infection (5R01MH113560-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201435. Licensed CC0.

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