Tobacco smoking effect on HIV-1 pathogenesis: role of cytochrome P450 isozymes. (November 2013)

• Record Type: Journal Article
• Authors: Ande, Anusha; McArthur, Carole; Kumar, Anil; Kumar, Santosh
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 9:Number 11(2013:Nov.)
• Page Start: 1453
• Page End: 1464
• Publication Date: 2013-11
• Subjects: Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1517/17425255.2013.816285
• Languages: English
• ISSNs: 1742-5255

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Tobacco smoking is highly prevalent among the HIV-1-infected population. In addition to diminished immune response, smoking has been shown to increase HIV-1 replication and decrease response to antiretroviral therapy, perhaps through drug–drug interaction. However, the mechanism by which tobacco/nicotine increases HIV-1 replication and mediates drug–drug interaction is poorly understood.</p> <p> <bold> <italic>Areas covered:</italic> </bold> In this review, the authors discuss the effects of smoking on HIV-1 pathogenesis. Since they propose a role for the cytochrome P450 (CYP) pathway in smoking-mediated HIV-1 pathogenesis, the authors briefly converse the role of CYP enzymes in tobacco-mediated oxidative stress and toxicity. Finally, the authors focus on the role of CYP enzymes, especially CYP2A6, in tobacco/nicotine metabolism and oxidative stress in HIV-1 model systems monocytes/macrophages, lymphocytes, astrocytes and neurons, which may be responsible for HIV-1 pathogenesis.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> Recent findings suggest that CYP-mediated oxidative stress is a novel pathway that may be involved in smoking-mediated HIV-1 pathogenesis, including HIV-1 replication and drug–drug interaction. Thus, CYP and CYP-associated oxidative stress pathways may be potential targets to develop novel pharmaceuticals for HIV-1-infected smokers. Since HIV-1/TB co-infections are common, future study involving interactions between antiretroviral and antituberculosis drugs that involve CYP pathways would also help treat HIV-1/TB co-infected smokers effectively.</p> </abstract>