Opioid-Mediated HIV-1 Immunopathogenesis
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INVITED REVIEW
Opioid-Mediated HIV-1 Immunopathogenesis Shilpa Buch 1 & Palsamy Periyasamy 1 Ashutosh Tripathi 1
&
Annadurai Thangaraj 1
&
Susmita Sil 1
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Ernest T. Chivero 1
&
Received: 22 March 2020 / Accepted: 14 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Despite the ability of combination antiretroviral therapy to dramatically suppress viremia, the brain continues to be a reservoir of HIV-1 low-level replication. Adding further complexity to this is the comorbidity of drug abuse with HIV-1 associated neurocognitive disorders and neuroHIV. Among several abused drugs, the use of opiates is highly prevalent in HIV-1 infected individuals, both as an abused drug as well as for pain management. Opioids and their receptors have attained notable attention owing to their ability to modulate immune functions, in turn, impacting disease progression. Various cell culture, animal and human studies have implicated the role of opioids and their receptors in modulating viral replication and virus-mediated pathology both positively and negatively. Further, the combinatorial effects of HIV-1/HIV-1 proteins and morphine have demonstrated activation of inflammatory signaling in the host system. Herein, we summarized the current knowledge on the role of opioids on peripheral immunopathogenesis, viral immunopathogenesis, epigenetic profiles of the host and viral genome, neuropathogenesis of SIV/SHIV-infected non-human primates, blood-brain-barrier, HIV-1 viral latency, and viral rebound. Overall, this review provides recent insights into the role of opioids in HIV-1 immunopathogenesis. Keywords Morphine . HIV-1 . Immunopathogenesis . Blood-brain barrier . Immunosuppression
Introduction HIV-1 prevalence continues to be a severe worldwide public health problem, with nearly 33 million people infected with HIV-1. Also, since the incidence of drug abuse among HIVinfected people is rapidly growing, there is an increased risk of the infected drug abusing people to develop HIV-associated neurocognitive disorders (HAND) compared to non-drug users infected with HIV-1. The Centers for Disease Control and Prevention describe HIV-1 infection and drug abuse as two intertwined epidemics, resulting in not only compromised combination antiretroviral therapy (cART) adherence but also to exacerbated pathogenesis of HAND. Among the several abused drugs, the use of opiates is highly prevalent in HIVinfected individuals, both as a recreational drug as well as for pain management (Atluri 2016; Basu et al. 2007; Hauser et al. 2012; Krashin et al. 2012; Lum and Tulsky 2006; Merlin et al. * Shilpa Buch [email protected] 1
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
2016; Noel et al. 2008). The interplay of HIV-1 and opiates thus raises concerns regarding the combinatorial effects of both on the progression of HAND. In recent years, chronic low-level inflammation likely mediated by residual viral proteins, abused drugs as well as lon
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