HIV-1 disease, substance abuse and HCV co-infection

Nirzari Parikh

doi:10.17918/00010230

Substance abuse, including the use of cocaine and cannabinoids, is a significant risk factor for exposure to human immunodeficiency virus type 1 (HIV-1) and the development of acquired immune deficiency syndrome, as well as hepatitis C virus (HCV) exposure, infection, and disease. HIV-1, along with HCV, share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Thus, co-infection with HIV-1 and HCV is common and may be impacted by chronic substance abuse during the course of disease. This thesis evaluated the relationship between illicit drug use and HIV-1 disease severity in HIV-1-infected patients enrolled in the DREXELMED HIV/AIDS Genetic Analysis Cohort, whose drug histories have been recorded longitudinally. Since, cocaine and cannabinoids are known to have immunomodulatory effects, the cytokine profiles of preferential non-users (PN), preferential cocaine (PCo) and preferential cannabinoid (PCa) users as well as multi-drug (MD) users were analyzed utilizing Luminex technology to understand the effects of drugs on cytokine modulation and HIV-1 disease severity. This analysis culminated in the development of a novel biostatistical model, which allowed defining the effects of specific drugs. Overall, PN and PCa users had better health as compared to PCo and MD users, with respect to normally assessed clinical parameters associated with HIV-1 disease and in fact, cannabinoids appeared to show a potential neuroprotective effect. Among the 30 cytokines investigated, differential levels of cytokines were established within these populations; cocaine use associated with an increase in Th2 cytokines, IL-4 and IL-10, and GM-CSF, while cannabinoid use associated with an increase in the Th1 collective panel as well the cytokines IL-113 and IL-1RA, and IL-2. Since over 40% of the cohort was co-infected with HCV, the impact of co-infection with HCV on the HIV-1 pathogenic process was compared in these patients. Comparing HIV-1 mono-infection with HIV-1/HCV co-infection allowed defining the detrimental effect of HCV co-infection as it relates to the associated immune response during the course of this complex interplay, in the background of substance abuse. Therefore, understanding the complex interplay between HIV-1, HCV, and drugs of abuse is essential to define HIV-1 disease within these patients.

HIV-1 disease, substance abuse and HCV co-infection

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HIV-1 disease, substance abuse and HCV co-infection

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