Doctor of Philosophy
Dayanjan (Shanaka) Wijesinghe
Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.
Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). After Tat induction, antiretrovirals (abacavir, dolutegravir, and lamivudine) ±morphine were continuously delivered for 5 days. Brains were harvested and cryosectioned and slices were imaged using IR-MALDESI-MSI. Multiple brain regions were examined.
The present study revealed that morphine exposure resulted in significantly decreased antiretroviral concentrations in the anterior and posterior brain sections. Interestingly, male mice experienced greater morphine-associated decreases in antiretroviral concentrations than females. The study also assessed whether changes in both antiretroviral and morphine concentrations were associated with areas of activated glia, using GFAP as a marker for glial activation. Differences in antiretroviral concentrations within areas of glial activation differed among treatments based on sex.
The findings from this study highlight the importance of monitoring opioid use in patients with HIV, as antiretroviral medications may become less efficacious within the CNS when co-exposed with opioids, which may contribute to the worsening of neuroHIV.
© The Author (Austin Matthew Jones)
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VCU Theses and Dissertations
Date of Submission
Available for download on Thursday, August 01, 2024
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