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Review
. 2019 Oct 18:10:2445.
doi: 10.3389/fimmu.2019.02445. eCollection 2019.

The Effects of Opioids on HIV Neuropathogenesis

Aniella Murphy  1 , John Barbaro  1 , Pablo Martínez-Aguado  1 , Vanessa Chilunda  1 , Matias Jaureguiberry-Bravo  1 , Joan W Berman  1   2
Affiliations
Review

The Effects of Opioids on HIV Neuropathogenesis

Aniella Murphy et al. Front Immunol. .

Abstract

HIV associated neurocognitive disorders (HAND) are a group of neurological deficits that affect approximately half of people living with HIV (PLWH) despite effective antiretroviral therapy (ART). There are currently no reliable molecular biomarkers or treatments for HAND. Given the national opioid epidemic, as well as illegal and prescription use of opioid drugs among PLWH, it is critical to characterize the molecular interactions between HIV and opioids in cells of the CNS. It is also important to study the role of opioid substitution therapies in the context of HIV and CNS damage in vitro and in vivo. A major mechanism contributing to HIV neuropathogenesis is chronic, low-level inflammation in the CNS. HIV enters the brain within 4-8 days after peripheral infection and establishes CNS reservoirs, even in the context of ART, that are difficult to identify and eliminate. Infected cells, including monocytes, macrophages, and microglia, produce chemokines, cytokines, neurotoxic mediators, and viral proteins that contribute to chronic inflammation and ongoing neuronal damage. Opioids have been shown to impact these immune cells through a variety of molecular mechanisms, including opioid receptor binding and cross desensitization with chemokine receptors. The effects of opioid use on cognitive outcomes in individuals with HAND in clinical studies is variable, and thus multiple biological mechanisms are likely to contribute to the complex relationship between opioids and HIV in the CNS. In this review, we will examine what is known about both HIV and opioid mediated neuropathogenesis, and discuss key molecular processes that may be impacted by HIV and opioids in the context of neuroinflammation and CNS damage. We will also assess what is known about the effects of ART on these processes, and highlight areas of study that should be addressed in the context of ART.

Keywords: HIV-associated neurocognitive disorders; buprenorphine; central nervous system; macrophages; monocytes; next generation sequencing; substance abuse.

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Figures

Figure 1
Figure 1
Potential therapeutic interventions for HAND in the context of opioid use and antiretroviral therapy (ART). (A) HIV induced neuroinflammation and viral seeding can be reduced by decreasing monocyte transmigration into the brain that is increased with opioid abuse. Buprenorphine and/or novel therapies developed using next generation sequencing (NGS) may reduce transmigration of HIV-infected and uninfected monocytes. (B) Current ART penetration into the brain does not eradicate viral reservoirs. Latency reactivating agents (LRA), ART, and opioid antagonists can be transported across the BBB and target infected cells in the CNS using liposomal nanoparticle delivery systems. (C) ART and CRISPR/Cas9 can be transported across the BBB to help eradicate HIV reservoirs using liposomal nanoparticle delivery systems. (D) scRNA-seq can be used to identify novel molecular mechanisms by which opioids and HIV infection increase CNS damage. These mechanisms can then be targeted to reduce HAND.
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