# Identification of Biomarkers of CNS injury and resilience related to HIV-1 and Methamphetamine

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $715,475

## Abstract

PROJECT SUMMARY
Methamphetamine (METH) is commonly abused and is a risk factor for HIV. METH also increases risk for
adverse outcomes during HIV, including HIV-associated neurocognitive disorder (HAND). Multiple studies
have demonstrated the neurotoxic effects of METH and HIV on brain structure and function, as well as
neurobehavioral and functional performance. Biomarkers of central nervous system (CNS) injury and resilience
would be valuable tools for understanding the METH- and HIV-associated pathogenesis and could provide
valuable insights for drug development. The effects of METH and HIV outside the CNS (e.g., vascular and
metabolic disease) are also important to consider and are a key gap in the field. Another key gap in the field
is the translation of research findings to the clinic, including biomarkers that may be used to detect METH- and
HIV-associated CNS injury and functional impairment across disease stages. Even less is known about
biomarkers of resilience of the host defense mechanisms. Thus, in response to RFA-DA-18-023, this project
proposes to screen a comprehensive panel of clinical and research biomarkers reflective of pathology and
resilience with the goal of identifying and validating biosignatures that may improve the clinical assessment
and diagnosis of brain and peripheral complications associated with METH and HIV. To accomplish this, we
propose to leverage NIDA’s prior investment in UCSD’s NIDA-funded Translational Methamphetamine AIDS
Research Center (TMARC), which performed standardized neurobehavioral, neuroimaging, and neuromedical
assessments of participants who differed by METH use and HIV infection. We will recall and comprehensively
re-assess 200 of these participants. Neuroimaging methods will include measures of cerebral blood flow, CNS
metabolite levels, and a novel neuroimaging measure to estimate integrity of the blood-brain barrier (BBB). We
will measure a comprehensive biomarker panel in blood, cerebrospinal fluid (CSF), and stool samples, in
specimens from their prior baseline visit, which are stored, and from their new visit and then analyze the data
using traditional statistical approaches as well as novel techniques rooted in machine-learning and causal
inference modeling. This approach will provide unique longitudinal data that will allow for the identification of
biosignatures that predict changes in CNS injury and resilience. We will validate the observed biosignatures
in an independent cohort of 100 participants who have been previously assessed at UCSD’s HIV
Neurobehavioral Research Program and who have comprehensive data and stored specimens (e.g., CSF)
available. To better respond to the clinical translation objective of the RFA, we will also compare measured
biomarkers to data that are obtained during routine clinic assessments with the goal of identifying a clinical
biosignature of METH- and HIV-related CNS injury. A thorough understanding of the impact of METH and HIV
on systemic and CNS pro...

## Key facts

- **NIH application ID:** 10189544
- **Project number:** 5R01DA047879-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jennifer E Iudicello
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $715,475
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189544

## Citation

> US National Institutes of Health, RePORTER application 10189544, Identification of Biomarkers of CNS injury and resilience related to HIV-1 and Methamphetamine (5R01DA047879-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10189544. Licensed CC0.

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