以往研究发现阿片类毒品成瘾者抗HIV-1药物治疗效果不佳，但是否由于阿片类物质对HIV-1耐药性有选择作用而引起尚有待阐明。我们前期体外研究发现阿片类物质可诱导HIV-1产生一线药物耐药性且缩短其耐药突变的时间。本课题在已有的队列人群基础上，组建阿片类物质使用和非阿片类物质使用HIV感染者的前瞻性队列，定期随访和采集血样，对HIV-1 PR和RT区基因进行扩增测序，进行基因型耐药分析，同时将目的基因插入骨架质粒，并和表达包膜蛋白的质粒共同转染至细胞，进行假病毒的构建和表型敏感性检测，以追踪队列人群体内HIV-1毒株抗病毒药物耐药性产生的时间、类型、耐药量值变化、耐药率等演变进程；结合流行病学资料，运用logistic回归分析方法，分析HIV-1耐药性产生的影响因素。本课题将在人群水平阐明阿片类物质对人体HIV-1抗一线药物耐药性的选择作用，为抗HIV-1药物治疗方案提供新的思路。

Previous studies have found that highly active antiretroviral therapy (HAART) was not very effective among opioid-drug addicts. Whether it is due to HIV-1 drug resistance induced by opioids was unclear yet. Our preliminary data from in vitro study showed that opioids can induce HIV-1 resistance to the first-line-drugs and shorten the mutation time to generate drug resistance. In this study, we will utilize an existing cohort and re-construct a prospective study to compare HIV-1 drug resistance between two populations: HIV-1-infected subjects with or without opioid-using history. Follow-up visits and blood sample collection will occur periodically. The protease (PR) and reverse transcriptase (RT) genes of HIV-1 strains in these samples will be separately amplified by RT-PCR and sequenced. The RT and PR sequences will be analyzed for the drug-resistant subtypes. Simultaneously, the drug-resistant genes will be cloned into HIV backbone plasmid, which will be co-transfected with plasmid encoding HIV-1 envelope proteins to cells for pseudovirus construction and phenotypic sensitive test to track the in vivo HIV-1 drug resistance in infected individuals The resistance generation time, resistant type, resistant rate, and the change of resistant dose will be examined at the predefined time points. Then the epidemiological data will be analyzed by logistic regression analysis to determine the key factors responsible for the generation of HIV-1 drug resistance. In summary, this study will clarify the selective effect of opioids on HIV-1 resistance to first-line-drugs at a population level and provide novel insights for HAART.