达菲污染江河？日本开始调查耐药性病毒

抗甲型H1N1流感药物达菲是否会通过江河，给环境带来污染？日本药剂师会（会长儿玉孝）开始了对全国的调查。

乙型肝炎病毒耐药性临床需知

应本刊的邀请,由美国密歇根大学国际知名肝病学家骆淑芳教授(Anna SF LOK)提供本文,她是AASLD乙型肝炎指南的主要执笔者。原文为英文,由本人根据本刊篇幅适当精炼。并补充恩替卡韦、替比夫定和替诺福韦的最新资料,请参阅:Hepatology,2006,44(2):309-313;44(2):318-325;44(6):1404-1407;44(6):1656-1665;Gastroenterology,2006,131(6)

世界卫生组织：人类免疫缺陷病毒耐药性可能会阻碍AIDS的有效治疗

2017年7月20日［路透社（凯特·凯兰德）］：世界卫生组织（WHO）表示，如果不尽早采取行动，人类免疫缺陷病毒（HIV）耐药水平上升可能阻碍全球应对AIDS流行的进程。研究人员发现，在接受调查的11个非洲、亚洲和拉丁美洲国家中的6个国家，有10%的HIV感染患者对目前广泛使用的抗反转录病毒药物产生了耐药性。WHO建议一旦达到10%的耐药率，应立即审查其目前的抗HIV治疗方案，并改用不同的治疗方案以限制耐药性的传播。如果患者不遵守规定的治疗方案，HIV对治疗药物就会产生耐药性，这种情况往往由于患者无法获得适当的抗HIV治疗和护理。来自AIDS规划署的最新数据显示，抗HIV/AIDS流行的进展令人鼓舞，AIDS病死率下降，治疗率上升。

抗丙型肝炎病毒药物治疗失败与丙型肝炎病毒耐药性

20世纪80年代早期,艾滋病的蔓延促进了抗病毒药物的研发。市场出现了针对不同靶点和机制的抗逆转录病毒药物。然而很快,病毒的耐药性就成为了长期抗病毒治疗的主要问题。丙型肝炎病毒（HCV）与艾滋病病毒（HIV）具有很多相似之处,

2016年-2017年吉安市乙型流感病毒基因特性分析

目的了解吉安市2016年-2017年乙型流感的流行状况,分析乙型流感毒株的基因变异特征及神经氨酸酶耐药情况,为预防和控制流感传播流行提供科学依据。方法对监测医院和疑似流感疫情采集的流感样病例鼻咽拭子标本进行流感病毒分离,并随机选择一部分分离到的乙型流感病毒进行核酸的提取,采用逆转录-聚合酶链反应(RT-PCR)扩增病毒基因后进行核苷酸序列测定,用生物信息学软件对测序结果进行分析处理,并分析基因特性。结果 8株Victoria系乙型毒株HA基因之间的同源性为99.3%～99.9%,NA基因之间的同源性为99%～99.8%,7株Yamagata系B型毒株HA基因之间的同源性为98.8%～99.8%,NA基因之间的同源性为98.3%～99.9%。与疫苗株相比,HA氨基酸变异数为1-4个之间。所有毒株的NA蛋白催化活性位点和辅助位点均未发生氨基酸替换。结论 2016年-2017年吉安市乙型流感HA基因未发生明显变异,且未发现神经氨酸酶耐药株。

河南省部分艾滋病患者抗病毒治疗的临床效果以及基因型耐药性分析

目的 了解河南省部分地区HIV 1感染者抗病毒治疗临床效果 ,分析服药依从性与治疗效果关系 ;与未进行抗病毒治疗的患者相比较 ,分析治疗后病毒耐药性突变发生和流行情况。方法通过问卷调查、CD4 +细胞测定评价抗病毒治疗的临床效果 ;用RT PCR方法扩增HIV 1 pol区基因 ,进行基因型耐药性分析。结果 接受抗病毒治疗的人群中 ,坚持服药的病人 55.0 8%病情明显好转 ,而未坚持服药的病人仅有 6 .78%病情明显好转 ,服药依从性对病情趋势变化具有显著影响 (P <0 .0 5) ;接受抗病毒治疗的病人CD4 +淋巴细胞均值为 ( 4 2 9.38± 7.89)个 /μl,未治疗的病人CD4 +淋巴细胞均值为( 2 0 1 .4 3± 8.72 )个 /μl,治疗后患者CD4 +淋巴细胞计数显著高于未治疗的患者 (P <0 .0 5) ;基因型耐药性检测结果表明 ,相对于未经治疗的患者 ,经过抗病毒治疗的患者对逆转录酶抑制剂的耐药性突变显著高于未治疗的患者 ( χ2 =1 9.4 2 85,P <0 .0 5) ;治疗人群与未治疗人群对蛋白酶抑制剂的耐药突变差异无统计学意义 ( χ2 =0 .3478,P <0 .50 ) ;耐药性突变主要发生在CD4 +淋巴细胞 <2 0 0个 /μl病人中。结论 用国产抗病毒药物治疗可取得较好的临床效果 ,服药依从性对治疗效果有重要影响 ,治疗后耐药性突变发生率显著升高 。

日研究称儿童服用“达菲”更易导致耐药病毒出现

日本一项最新研究显示，作为治疗流感药物而得到广泛使用的‘‘达菲”与另一种抗病毒药物“扎那米韦”相比，更容易导致患流感儿童体内出现耐药性病毒。

乙肝病毒耐药变异的监测与预防

耐药变异是乙肝病毒经过抗病毒药物的选择,逐渐对治疗药物失去敏感性,从而产生抗药性的过程.乙肝病毒耐药性的出现是悄无声息的,因此我们无法在第一时间发现.只有当耐药的乙肝病毒繁殖到一定数量,才能通过现有的HBV一DNA检测技术发现.这就是所谓的“病毒学突破”或者“病毒反弹”.

PI变异的数量和类型决定病毒学应答

据Medscape．com5月8日报道（原载AIDS 2006：20：847—853）.通过检测蛋白酶抑制剂（PI）变异株的数量和类型可预测HIV对抗病毒药物的病毒学应答。 美国马里兰食品和药品监督管理局的Naeger博士指出。了解HIV病人抗逆转录病毒耐药性的出现对选择下一步的治疗是很关键的。在经过治疗的病人中。他观察了在HIV对Atazanavir／利托那韦应答中基线蛋白酶基因型和表型的作用。在Atazanavir／利托那韦治疗的患者中。其PI相关性耐受位点M46、G73、184、L90发生替换。抗病毒应答率低于30％。但是D30N、M36I／V、V77I、N88S／D的出现并未影响对Atazanavir／利托那韦的应答。这一结果显示当出现三种或三种以上的PI变异株时。应答率从60％下降到40％。在出现五种或五种以上PI变异株处于基线水平的患者中无应答者。如果存在三种或更多的主要基线PI变异株。

HIV-1耐药产生机制及其临床应用

自1996年高效抗逆转录病毒治疗（highlv actire antiretroviral therapy，HAART）应用于艾滋病（acquired immunodeficiency syndrome，AIDS）临床治疗已有10年时间。10年来AIDS的发病率和病死率明显下降，患者生存质量得到了显著改善，但病毒耐药性的出现则大大削弱了HAART抑制病毒复制的作用，降低了抗病毒治疗效果。

HIV化学治疗的最新进展

分两部分介绍了抗HIV的化学治疗药物的新进展,一是作用于现有病毒靶位的属于逆转录酶抑制剂和蛋白酶抑制剂的新化合物,另一部分是作用于病毒新靶位的化合物如HIV整合酶抑制剂、核糖核酸酶H抑制剂以及病毒进入抑制剂。主要从化学结构、对耐药性病毒的抑制作用、作用机制和临床效果等几个方面介绍了解决HIV耐药性问题的新化合物。

Indinavir Resistance Evolution in One Human Immunodeficiency Virus Type 1 Infected Patient Revealed by Single-Genome Amplification

Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.

Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Nucleos(t)ide analogues(NA) are a breakthrough in the treatment and management of chronic hepatitis B.NA could suppress the replication of hepatitis B virus(HBV) and control the progression of the disease.However,drug resistance caused by their long-term use becomes a practical problem,which influences the long-term outcomes in patients.Liver transplantation is the only choice for patients with HBV-related end-stage liver disease.But,the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients.Recently,the multi-drug resistance(MDR) has become a common issue raised due to the development and clinical application of a variety of NA.This may complicate the antiviral therapy and bring poorly prognostic outcomes.Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR,the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy.The future of HBV researches relies on how toprevent the MDR occurrence and develop reasonable and effective treatment strategies.This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

Prevalence and patterns of drug-resistance mutations among HIV-1 patients infected with CRF07_BC strains in Sichuan province,China

Little information is available on the prevalence of drug-resistance mutations in patients harboring the human immunodeficiency virus type 1(HIV-1) circulating recombinant form(CRF)07_BC variant in Sichuan, China. This study examined 375 plasma samples from patients with HIV-1 who were infected with the CRF07_BC strain, including 104 drug-naive participants and 271 in whom antiretroviral therapy(ART) had failed. Only one participant in the drug-naive group had a drug-resistance mutation(M46L), compared with 31.73% of those in whom ART had failed. Further analysis showed that 19.56% of strains contained mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors(NNRTIs) alone, 0.74% were resistant to nucleoside reverse transcriptase inhibitors(NRTIs) alone, and 11.44% were dual-resistant to both NRTIs and NNRTIs. The most common mutation in the ART-failure group was M184V(35.88%), K103N(45.01%), Y181C(17.33%), and G190S/A(15.88%). The percentages of HIV-1 strains resistant to lamivudine, emtricitabine, efavirenz, etravirine, and nevirapine were 10.70%, 10.70%, 28.04%, 7.75%, and 26.20%, respectively. To explore site variants possibly related to drug resistance, variations in the ancestor/consensus CRF07_BC sequences from the therapy-naive and ART-failure groups were compared, and seven mutations at six positions were identified as being significantly differently distributed between the two groups(p<0.05). Detailed sequence data will provide information on CRF07_BC genetic characterizations, and improve our understanding of antiretroviral susceptibility and the evolution of drug-resistance mutations. This will be valuable in developing and implementing local public-health approaches for HIV drug-resistance prevention and treatment.

2005年第3届HIV致病机理与治疗IAS国际会议报道 一、对晚期暴发者值得期待的药物治疗及耐药问题

可传播的药物耐受性与疾病进展 A．M．J Wensing发表了有关快速疾病进展与病毒耐药性之间关系的一项报道，该报道来自荷兰和比利时。纽约时报上报道了一宗有关一名男同性恋发生性关系而感染了HIV的多重耐药株并且在4-20月期间从传染期快速进展为进展期AIDS的病例。这一病例提出了有关一个高毒力多重耐药株HIV已经出现并被传播的担忧。