Morphine Increases Lamivudine- and Nevirapine-Induced Human Immunodeficiency Virus-1 Drug-Resistant Mutations In Vitro
Morphine Increases Lamivudine- and Nevirapine-Induced Human Immunodeficiency Virus-1 Drug-Resistant Mutations In Vitro
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吗啡可增加拉米夫定和奈韦拉平诱导的人类免疫缺陷病毒 1 体外耐药突变
DOI：
10.1089/mdr.2015.0347
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发表时间：
2017-04-01
影响因子：
2.6
通讯作者：
Ye, Li
中科院分区：
文献类型：
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作者：
Liang, Bingyu;Jiang, Junjun;Ye, Li
流行病学研究表明，注射吸毒者中人类免疫缺陷病毒（HIV-1）耐药率高于其他HIV-1阳性人群，一般认为这主要是由于临床不依从。然而，人们对海洛因滥用是否对HIV-1耐药突变的产生有直接影响知之甚少。本研究通过体外HIV-1-CD 4（+）T细胞系统，在两种典型抗病毒药物拉米夫定和奈韦拉平的选择压力下，研究海洛因的活性代谢产物吗啡对HIV-1感染/复制和HIV-1耐药突变的影响。我们发现吗啡处理MT 4细胞（一种CD 4（+）T细胞系）显著增加了HIV-1 III B（一种T嗜性病毒株）在MT 4细胞中的感染和复制，吗啡对HIV-1的作用是通过阿片受体介导的。更重要的是，我们的研究结果表明，与单独使用抗逆转录病毒药物的对照组相比，吗啡治疗不仅在抗逆转录病毒药物的选择压力下诱导了更多的耐药突变，而且缩短了突变的产生时间。虽然体内相关性仍有待确定，这些研究结果提供了直接的体外证据，以支持海洛因滥用本身可以作为一个独立的因素，有助于在临床抗逆转录病毒治疗的HIV-1耐药性的产生的可能性。治疗指南应考虑到感染艾滋病毒的海洛因使用者的这一问题。
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.