HIV-1, HCV and Alcohol in the CNS: Potential Interactions and Effects on Neuroinflammation

Approximately 25% of the HIV-1 positive population is also infected with HCV. The effects of alcohol on HIV-1 or HCV infection have been a research topic of interest due to the high prevalence of alcohol use in these infected patient populations. Although it has long been known that HIV-1 infects the brain, it has only been a little more than a decade since HCV infection of the CNS has been characterized. Both viruses are capable of infecting and replicating in microglia and increasing the expression of proinflammatory cytokines and chemokines, including IL-6 and IL-8. Investigations focusing on the effects of HIV-1, HCV or alcohol on neuroinflammation have demonstrated that these agents are capable of acting through overlapping signaling pathways, including MAPK signaling molecules. In addition, HIV-1, HCV and alcohol have been demonstrated to increase permeability of the blood-brain barrier. Patients infected with either HIV-1 or HCV, or those who use alcohol, exhibit metabolic abnormalities in the CNS that result in altered levels of n-acetyl aspartate, choline and creatine in various regions of the brain. Treatment of HIV/HCV co-infection in alcohol users is complicated by drug-drug interactions, as well as the effects of alcohol on drug metabolism. The drug-drug interactions between the antiretrovirals and the antivirals, as well as the effects of alcohol on drug metabolism, complicate existing models of CNS penetration, making it difficult to assess the efficacy of treatment on CNS infection.