Effect of Opioid Use on Immune Activation and HIV Persistence on ART
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INVITED REVIEW
Effect of Opioid Use on Immune Activation and HIV Persistence on ART Livio Azzoni 1 & David Metzger 2 & Luis J. Montaner 1 Received: 10 July 2020 / Accepted: 14 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract While there is an emerging consensus that engagement of the Mu opioid receptor by opioids may modulate various stages the HIV life cycle (e.g.: increasing cell susceptibility to infection, promoting viral transcription, and depressing immune responses to virally-infected cells), the overall effect on latency and viral reservoirs remains unclear. Importantly, the hypothesis that the increase in immune activation observed in chronic opioid users by direct or indirect mechanisms (i.e., microbial translocation) would lead to a larger HIV reservoir after ART-suppression has not been supported to date. The potential for a subsequent decrease in reservoirs after ART-suppression has been postulated and is supported by early reports of opioid users having lower latent HIV burden. Here, we review experimental data supporting the link between opioid use and HIV modulation, as well as the scientific premise for expecting differential changes in immune activation and HIV reservoir between different medications for opioid use disorder. A better understanding of potential changes in HIV reservoirs relative to the engagement of the Mu opioid receptor and ART-mediated immune reconstitution will help guide future cure-directed studies in persons living with HIV and opioid use disorder. Keywords (4–6) Opioid use disorder . Medications of opioid use disorder . HIV latent reservoir . ART suppression . Immune reconstitution . Microbial translocation
Introduction Opioid administration is known to negatively affect the host immune defenses, leading to increased susceptibility to infections such as pneumonia or, in the case of persons who inject drugs (PWIDs), endocarditis, osteomyelitis, septic arthritis and epidural abscesses (Ronan and Herzig 2016; Edelman et al. 2019; Schranz et al. 2019; Visconti et al. 2019). This has led to an increased overall prevalence of hospitalizations related to infectious diseases in PWIDs [(Ronan and Herzig 2016); reviewed in (Reardon 2019)]. Indeed, opioids can directly affect immune function by interacting with cell surface receptors (e.g. μ opioid receptor, MOR) on immune effectors, * Luis J. Montaner [email protected] 1
HIV Immunopathogenesis Laboratory, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
2
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, 3535 Market Street, Suite 4100, Philadelphia, PA 19104, USA
inducing the secretion of pro-inflammatory cytokines, reducing Natural Killer (NK) cell activity, impairing T helper type 1 (Th-1) responses, and reducing antibody production. In addition, chronic opioid use leads to chronic constipation, dysbiosis and alterations of the mucosal barrier, and microbial translocation, all of which results in increased immune activation and
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