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Review
. 2015 Jun;10(2):217-32.
doi: 10.1007/s11481-015-9599-8. Epub 2015 Mar 21.

Behavioral, Metabolic, and Immune Consequences of Chronic Alcohol or Cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV Model

Patricia E Molina  1 , Angela M Amedee, Peter Winsauer, Steve Nelson, Gregory Bagby, Liz Simon
Affiliations
Review

Behavioral, Metabolic, and Immune Consequences of Chronic Alcohol or Cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV Model

Patricia E Molina et al. J Neuroimmune Pharmacol. 2015 Jun.

Abstract

HIV-associated mortality has been significantly reduced with antiretroviral therapy (ART), and HIV infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (Azar et al. Drug Alcohol Depend 112:178-193, 2010; Phillips et al. J Gen Int Med 16:165, 2001). Alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of HIV infection, as well as the ability of the virus to integrate into the genome and replicate in host cells. Identifying mechanisms responsible for these interactions is complicated by many factors, such as the tissue specific responses to viral infection, multiple cellular mechanisms involved in inflammatory responses, neuroendocrine and localized responses to infection, and kinetics of viral replication. An integrated physiological analysis of the biomedical consequences of chronic alcohol and drug use or abuse on disease progression is possible using rhesus macaques infected with simian immunodeficiency virus (SIV), a relevant model of HIV infection. This review will provide an overview of the data gathered using this model to show that chronic administration of two of the most commonly abused substances, alcohol and cannabinoids (Δ(9)-Tetrahydrocannabinol; THC), affect host-pathogen interactions.

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Figures

Figure 1
Figure 1
Salient lessons learned using an integrated biological systems approach to examine the impact of alcohol and cannabinoids on SIV disease progression. The non-human primate model helped identify some of the underlying mechanisms that determine disease progression and how these are affected by alcohol and drugs of abuse under controlled conditions. This model has also allowed us to contrast the different phenotypes of disease progression produced by alcohol and the cannabinoids.
Figure 2
Figure 2
The most relevant effects identified during the investigation of the interaction of chronic binge alcohol administration with SIV disease progression were decreased mucosal immunity and increased viral replication, changes in metabolic regulation, and increased disruption of neurobehavioral functions.
Figure 3
Figure 3
The most relevant effects identified during the investigation of the interaction of chronic Δ9-THC administration with SIV disease progression were suppressed inflammation and decreased viral replication.
Figure 4
Figure 4
Summary of the principal mechanisms of alcohol- and cannabinoid-induced modulation of SIV disease progression in male rhesus macaques.
See this image and copyright information in PMC

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