Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis

Role of cytochrome P450 isozymes

Santosh Kumar, Mengyao Jin, Anusha Ande, Namita Sinha, Peter S. Silverstein, Anil Kumar

Research output: Contribution to journalReview article

34 Citations (Scopus)

Abstract

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 alcoholPI 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.

Original languageEnglish (US)
Pages (from-to)1363-1375
Number of pages13
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume8
Issue number11
DOIs
StatePublished - Nov 1 2012

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Highly Active Antiretroviral Therapy
Alcohol Drinking
Cytochrome P-450 Enzyme System
Isoenzymes
HIV-1
Alcohols
Protease Inhibitors
Oxidative stress
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2E1
Oxidative Stress
Reverse Transcriptase Inhibitors
Astrocytes
Macrophages
Monocytes
Metabolism
Therapeutics
Expert Testimony
HIV Infections
Acquired Immunodeficiency Syndrome

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis : Role of cytochrome P450 isozymes. / Kumar, Santosh; Jin, Mengyao; Ande, Anusha; Sinha, Namita; Silverstein, Peter S.; Kumar, Anil.

In: Expert Opinion on Drug Metabolism and Toxicology, Vol. 8, No. 11, 01.11.2012, p. 1363-1375.

Research output: Contribution to journalReview article

Kumar, Santosh ; Jin, Mengyao ; Ande, Anusha ; Sinha, Namita ; Silverstein, Peter S. ; Kumar, Anil. / Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis : Role of cytochrome P450 isozymes. In: Expert Opinion on Drug Metabolism and Toxicology. 2012 ; Vol. 8, No. 11. pp. 1363-1375.
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