January 10, 2022
The current opioid epidemic has seen the rise of fentanyl among people who inject drugs (PWID) and has led to unprecedented challenges in the management and recovery of these individuals. Furthermore, the incidence of Human Immunodeficiency Virus (HIV) infection in PWID has increased simultaneously, leading to comorbid conditions. In the age of antiretroviral therapy, HIV infection in peripheral immune cells is kept in check. However, neurological complications called HIV-associated neurocognitive disorders (HAND) persist. Therefore, it is imperative to understand how rising synthetic opioid use can affect the neuropathogenesis of HAND. Our long-term goal is to understand how contemporary opioids affect HIV proviral transcription in microglia, leading to clearly defined harm reduction and recovery strategies for HIV positive PWID. The objective of this grant is to utilize novel model systems to specifically determine the change in HIV proviral transcription and neuronal functionality after treatment with fentanyl, and other opioids used for recreation or recovery. The central hypothesis is that opioid use exacerbates HIV mediated neuronal pathogenesis by activating HIV proviral transcription. Our specific aims will test the central hypothesis by 1) Examining the effects of fentanyl, oxycodone, methadone, and buprenorphine on HIV proviral transcription in HIV NanoLuc CHME-5 immortalized microglia, and 2) determining the effects of oxycodone, fentanyl, methadone and buprenorphine on an in vitro model of neuronal dysfunction. The proposed research is innovative because studies have yet to explore the effects of fentanyl in the context of HIV proviral transcription and resulting neuronal functionality. Overall, these aims are significant because they will lead to the development of a pharmacological profile of specific opioids on HIV proviral transcription, which has not been characterized.