Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes

Introduction: Alcohol consumption, which is highly prevalent in HIV-infected individuals, poses serious concerns in terms of rate of acquisition of HIV-1 infection, HIV-1 replication, response to highly active antiretroviral therapy (HAART) and AIDS/neuroAIDS progression. However, little is known about the mechanistic pathways by which alcohol exerts these effects, especially with respect to HIV-1 replication and the patient's response to HAART. Areas covered: In this review, the authors discuss the effects of alcohol consumption on HIV-1 pathogenesis and its effect on HAART. They also describe the role of cytochrome P450 2E1 (CYP2E1) in alcohol-mediated oxidative stress and toxicity, and the role of CYP3A4 in the metabolism of drugs used in HAART (i.e., protease inhibitors ( PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI)). Based on the most recent findings the authors discuss the role of CYP2E1 in alcohol-mediated oxidative stress in monocytes/macrophages and astrocytes, as well as the role of CYP3A4 in alcohol-PI interactions leading to altered metabolism of PI in these cells. Expert opinion: The authors propose that alcohol and PI/NNRTI interact synergistically in monocytes/macrophages and astrocytes through the CYP pathway leading to an increase in oxidative stress and a decrease in response to HAART. Ultimately, this exacerbates HIV-1 pathogenesis and neuroAIDS.