TY - JOUR T1 - Methylnaltrexone Antagonizes Opioid-Mediated Enhancement of HIV Infection of Human Blood Mononuclear Phagocytes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1158 LP - 1162 DO - 10.1124/jpet.103.056697 VL - 307 IS - 3 AU - Wen-Zhe Ho AU - Chang-Jiang Guo AU - Chun-Su Yuan AU - Steven D. Douglas AU - Jonathan Moss Y1 - 2003/12/01 UR - http://jpet.aspetjournals.org/content/307/3/1158.abstract N2 - Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. We and others have recently demonstrated that opioid enhances HIV infection of human macrophages through modulation of β-chemokines and the CCR5 receptor and that this effect is reversed by naltrexone, a tertiary opioid antagonist. Tertiary opioid antagonists cannot be used in opioid-dependent patients because they precipitate withdrawal or reversal of analgesia. We determined whether the quaternary opioid antagonist methylnaltrexone (MNTX), now in phase III clinical trials for opioid-induced constipation, reverses the opioid-mediated enhancement of HIV infection of macrophages at clinically relevant doses. MNTX completely abrogated morphine-induced HIV Bal strain infection of macrophages. MNTX also inhibited the R5 strain (ADA) envelope-pseudotyped HIV replication induced by morphine. Furthermore, MNTX abolished morphine-mediated up-regulation of CCR5 receptor expression. The ability of MNTX to block opioid-induced CCR5 expression and HIV replication at clinically relevant doses may have additional benefit for opioid abusers with HIV infection, or patients with AIDS pain receiving opioids. The American Society for Pharmacology and Experimental Therapeutics ER -