title: Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Missouri Kansas City, School of Pharmacy, 2464 Charlotte St., Kansas City, MO 64108, USA. kumarsa@umkc.edu
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Mengyao
authors.initials: M
authors.lastname: Jin
authors.forename: Anusha
authors.initials: A
authors.lastname: Ande
authors.forename: Namita
authors.initials: N
authors.lastname: Sinha
authors.forename: Peter S
authors.initials: PS
authors.lastname: Silverstein
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004361:Drug Tolerance; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011480:Protease Inhibitors / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014779:Virus Replication
chemical_list: D017320:HIV Protease Inhibitors; D007527:Isoenzymes; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human