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

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. 2010; Phillips et al. 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 (Δ9-Tetrahydrocannabinol; THC), affect host-pathogen interactions.

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

“…Unlike cannabinoids and other addictive drugs of abuse, alcohol, does not appear to bind to a specific receptor ( Peter et al, 2008 ). In summary alcohol and cannabinoids have been shown to induce neuro-immune-modulatory consequences during healthy conditions and during HIV infection and disease progression as highlighted in several recent reviews ( Chang et al, 2014 ; Molina et al, 2015 ; Nair et al, 2015 ). Our current findings were able to highlight a divergent role of both substances in HIV infection and integration of human MDDC, and along with future studies, will allow us to elucidate the immunological consequences of alcohol and/or cannabinoids on the innate and adaptive immune system of an immune-compromised host.…”

“…Since the discovery of the Human Immunodeficiency Virus (HIV), the acquired immunodeficiency syndrome (AIDS) epidemic has been consistently associated with substance abuse and in some cases substance abuse treatment has been proposed as AIDS prevention ( Metzger et al, 1998 ; Volkow, 2012 ). Recently, the common problems associated with HIV and substance abuse comorbidities have been extensively discussed as demonstrated by the review of studies in humans and animal models ( Chang et al, 2014 ; Molina et al, 2015 ). In the context of alcohol abuse and HIV comorbidity, a higher prevalence (42%) of alcohol problems in HIV-infected patients compare to the prevalence in non-HIV patients has been reported using the CAGE questionnaire ( Samet et al, 2004 ).…”

“…Therefore, studies on the effects of substances of abuse such as alcohol and marijuana and their immune-modulatory mechanisms of action on HIV infection and disease progression are increasingly on demand since it is evident that the use of recreational substances such as alcohol and marijuana is common in this population and the consequences of substance abuse on HIV infection remain unclear. As previously reviewed most of the literature has highlighted the independent role of alcohol or marijuana on HIV ( Chang et al, 2014 ; Nair and Agudelo, 2014 ; Molina et al, 2015 ; Nair et al, 2015 ); however, a side by side comparison of the in vitro effects of alcohol and the role of cannabinoid compounds such as tetrahydrocannabinol (THC) and the synthetic cannabinoid, JWH-015, on HIV infection of monocyte-derived dendritic cells (MDDC) has not been explored.…”

Does alcohol use have a causal effect on HIV incidence and disease progression? A review of the literature and a modeling strategy for quantifying the effect

“…With respect to biological impacts, there seems to be clear evidence that heavy drinking or alcohol use disorders are associated with viral load increases and/or CD4 count declines, general weakening of the immune system, and more negative outcomes of antiretroviral therapy (ART), partly mediated by treatment adherence and partly by the pharmacological interactions of alcohol with ART and other medications to treat co-morbidities (for the association regarding adherence see above; for the other associations see for heavy drinking: [ 46 , 66 ]; for AUD: [ 16 ]; for mechanisms see [ 20 , 46 , 48 , 67 , 68 ]; for pharmacological interactions see [ 69 , 70 ]). It should be noted, however, that delineation of causality in these biological pathways is difficult, as many factors interact, and even when causality has potentially been established, it is hard to quantify the causal contribution of alcohol to HIV/AIDS disease progression based on biological mechanisms [ 20 , 66 – 68 , 71 ].…”

Confirmed marijuana use and lymphocyte count in black people living with HIV

“…Demographic and physiological covariates that may confound a significant relationship between marijuana use and immune function were selected based on published literature. Specifically, age (Ader et al, 1990), sex (Keen and Turner, 2015), body mass index (Molina et al, 2015), and income (Galea et al, 2007) were included in the analysis of covariance. Additionally, analyses of covariance included HIV-related covariates.…”