DOI
https://doi.org/10.25772/AJ5K-SA28
Author ORCID Identifier
0000-0001-5736-1008
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pharmaceutical Sciences
First Advisor
Mary Peace McRae, Pharm.D., Ph.D.
Second Advisor
Kurt Hauser, Ph.D.
Third Advisor
Joseph McClay, Ph.D.
Fourth Advisor
Katherine Nicholson, Ph.D., D.V.M.
Fifth Advisor
Julie Patterson, Pharm.D., Ph.D.
Sixth Advisor
Dayanjan Wijesinghe, Ph.D.
Abstract
Even after the advent of antiretroviral therapy, over 40% of people with HIV (PWH) experience cognitive impairment due to HIV-induced neuroinflammation. Illicit opioid dependence exacerbates HIV neuropathology. Treating opioid use disorder (OUD) in PWH improves HIV outcomes (e.g., viral load, mortality). However, the two main treatments for OUD, buprenorphine and methadone, are also opioids and it is unknown how they affect neurocognitive or neuroinflammatory outcomes in the context of HIV.
Secondary analyses were used to assess the effect of cumulative opioid use on cognitive outcomes, the effect of comorbidity burden on OUD treatment initiation and retention, and compare the effect of buprenorphine versus methadone on cognitive outcomes in PWH. A 29-marker flow cytometry panel was used to profile and compare immune response in the brain of an EcoHIV mouse model treated with either buprenorphine or methadone.
We found that greater cumulative opioid use was associated with worse cognitive outcomes regardless of HIV status. Additionally, PWH who used opioids had worse cognitive outcomes than people without HIV who used opioids. Greater comorbidity burden decreased likelihood of OUD treatment initiation. Furthermore, PWH treated with buprenorphine were less likely to develop a diagnosis of dementia than those treated with methadone. Differences were also seen in neuroimmune response in EcoHIV mice treated with either buprenorphine or methadone.
In summary, limiting cumulative opioid exposure, increasing access to OUD treatment, and considering the neurocognitive and neuroinflammatory consequence of treatments for OUD are important when providing care to PWH and OUD.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
4-24-2025