title: Morphine Increases Lamivudine- and Nevirapine-Induced Human Immunodeficiency Virus-1 Drug-Resistant Mutations In Vitro.
abstract: Epidemiological studies have demonstrated that the human immunodeficiency virus (HIV)-1 drug-resistant rate among injecting drug users is higher than that in other HIV-1-positive populations, which is generally believed to be largely due to clinical nonadherence. Little is known, however, about whether heroin abuse has a direct impact on the generation of HIV-1 drug-resistant mutations. In this study, we investigated the impacts of morphine, the active metabolite of heroin, on HIV-1 infection/replication and HIV-1 drug-resistant mutations through an in vitro HIV-1-CD4+T cell system under selective pressure from two typical antiviral drugs, Lamivudine and Nevirapine. We found that morphine treatment of MT4 cells (a CD4+T cell line) significantly increased HIV-1 III B (a T-tropic viral strain) infection and replication in MT4 cells, and the effect of morphine on HIV-1 was mediated through an opioid receptor. More importantly, our results showed that morphine treatment not only induced more drug-resistant mutations under selective pressure from antiretroviral drugs but also shortened the mutations' generation time, compared with the control groups that were treated with antiretroviral drugs alone. Although the in vivo relevance remains to be determined, these findings provide direct in vitro evidence to support the possibility that heroin abuse itself can act as an independent factor contributing to the generation of HIV-1 drug resistance during clinical antiretroviral therapy. Therapeutic guidelines should consider this issue for heroin users with HIV infection.
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .|2 Life Sciences Institute, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, China .
authors.forename: Bingyu
authors.initials: B
authors.lastname: Liang
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .|2 Life Sciences Institute, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, China .
authors.forename: Junjun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .|3 Institute of Acute Communicable Diseases Prevention and Control , Guangxi Center for Diseases Prevention and Control, Nanning, China .
authors.forename: Peijiang
authors.initials: P
authors.lastname: Pan
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .
authors.forename: Rongfeng
authors.initials: R
authors.lastname: Chen
authors.affiliation: 4 State Key Laboratory of Pathogen and Biosecurity, Department of AIDS Research, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Daomin
authors.initials: D
authors.lastname: Zhuang
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .
authors.forename: Fangning
authors.initials: F
authors.lastname: Zhao
authors.affiliation: 5 Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning, China .
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .|2 Life Sciences Institute, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, China .
authors.forename: Jiegang
authors.initials: J
authors.lastname: Huang
authors.affiliation: 6 Center for AIDS Research, The Affiliated Ruikang Hospital of Guangxi Traditional Chinese Medical University , Nanning, China .
authors.forename: Qijian
authors.initials: Q
authors.lastname: Su
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .
authors.forename: Cunwei
authors.initials: C
authors.lastname: Cao
authors.affiliation: 4 State Key Laboratory of Pathogen and Biosecurity, Department of AIDS Research, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Jingyun
authors.initials: J
authors.lastname: Li
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .|2 Life Sciences Institute, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, China .
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.affiliation: 1 Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University , Nanning, China .|2 Life Sciences Institute, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, China .
authors.forename: Li
authors.initials: L
authors.lastname: Ye
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D002460:Cell Line; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009154:Mutation / Q000187:drug effects* / Q000235:genetics; D019829:Nevirapine / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D009020:Morphine; D019829:Nevirapine
keywords: HIV-1; Lamivudine; Nevirapine; drug resistance; morphine