PII-040 - THE IMPACT OF HIV-1 TAT AND MORPHINE ON SPATIAL DISTRIBUTION OF DRUGS IN THE BRAIN.

A. Jones¹, K. Rademeyer², S. Contaifer², E. Rosen³, D. Wijesinghe², K. Hauser², M. McRae⁴; ¹University of Virginia, Charlottesville, VA, United States, ²Virginia Commonwealth University, ³University of North Carolina at Chapel Hill, ⁴University of Virginia.

Background: Opioid use worsens neuroHIV and associated cognitive impairment in people with HIV. This study examined the effects of opioid use on antiretroviral and morphine distribution within the brain as a potential mechanism by which opioids worsen HIV outcomes within the brain.

Methods: 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) with or without 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.

Results: Morphine, regardless of Tat status, significantly decreased abacavir concentrations in all regions except the nucleus accumbens (p < 0.05). Males had significant decreases in abacavir concentrations in morphine-treated mice (as compared to control) in nine brain regions, where females had decreased abacavir concentrations in only four brain regions. Additionally, Tat status influenced morphine abundance within the anterior brain section, with Tat(+) mice having higher morphine than Tat(-) mice (p < 0.0021).

Conclusion: These data suggest that opioid use people with HIV may result in poor viral suppression within the brain, which may contribute to worsening of neuroHIV.