HIV-1耐药基因检测的研究进展

HIV-1耐药是影响艾滋病抗病毒治疗效果的主要因素。随着抗病毒疗法的普及和接受治疗者的增多,HIV-1耐药的问题日益凸显,使艾滋病治疗面临巨大的挑战。因此,了解各抗病毒药物治疗引起的HIV-1耐药突变位点并及时采用有效方法进行耐药基因检测对临床治疗具有重要指导意义。HIV-1耐药位点基因型检测方法因其快速准确的特点,目前是HIV-1耐药检测最常用也是最有前景的方法。本文对HIV-1耐药位点和耐药基因检测的研究进展做简单综述。     

HIV-1获得性耐药研究进展

HIV-1耐药性影响艾滋病的传播、治疗和预后,随着发现即治疗政策的全面推广,艾滋病治疗人数不断增加,HIV-1耐药已经成为越来越重要的公共卫生问题。HIV-1耐药包括传播性耐药和获得性耐药,传播性耐药指HIV感染者未经抗病毒治疗就发生的耐药,而获得性耐药指艾滋病病人接受抗病毒治疗后产生的耐药。本文拟从HIV-1获得性耐药现状,耐药位点分布、耐药检测方法、耐药结果解释系统和耐药产生的原因等方面进行文献整理,对我国的艾滋病抗病毒治疗和耐药监测工作有一定的参考作用。     

广西新诊断HIV/AIDS患者HIV-1整合酶区基因突变及整合酶抑制剂耐药分析

目的 了解广西新诊断HIV-1感染者整合酶抑制剂（integrase stand transfer inhibitors,INSTIs）耐药率、HIV-1整合酶区耐药相关多态性位点的突变率及影响因素。方法 使用课题组2019年10月—2020年3月收集的广西新诊断HIV/AIDS患者血液样本，提取HIV-1整合酶区RNA、巢式PCR扩增整合酶基因并测序。利用斯坦福HIV耐药数据库确定患者HIV-1整合酶区耐药突变位点并计算患者耐药率。通过序列比对分析HIV-1整合酶区耐药相关多态性突变位点，使用多因素logistic回归分析HIV-1整合酶区耐药相关多态性位点发生突变的影响因素。结果 320例HIV-1患者的HIV-1整合酶区序列中，以CRF01＿AE亚型（39.4%）为主，耐药率为2.19%，主要耐药突变位点为E92K(0.62%),次要耐药突变位点主要为E157Q(1.25%)。发生频率较高的HIV-1整合酶区耐药相关多态性位点有L74V(0.94%)、E138D(1.25%)和G163E(3.13%)。多因素logistic回归分析显示：HIV-1整合酶区耐药相关多态性突变的影响...     

江苏省HIV-1基因型抗病毒治疗失败患者耐药检测结果分析

目的了解江苏省2010—2014年HIV-1感染者抗病毒失败人群的HIV-1耐药情况,为临床抗病毒治疗提供参考。方法根据耐药检测实验室网络收集江苏省2010—2014年的HIV-1基因型耐药检测结果,对各年度相关药物耐药情况、耐药基因位点及病毒基因亚型进行统计分析。结果 2010—2014年分别纳入样本74、113、197、278、346份,其中检测出现耐药结果的比率分别为68.92%、48.67%、51.27%、52.52%和57.80%。各年度间HIV-1主要耐药药物类似,核苷类主要有3TC、ABC、DDI和FTC,非核苷类药物以EFV和NVP为主。HIV-1对蛋白酶类药物耐药差别较大,且目前使用的LPV/r的耐药率在1%以下。年度间HIV-1主要耐药位点为184、181、190及103位,其中184位突变主要引起3TC和FTC耐药,而181、190、103位突变与EFV和NVP耐药相关。HIV-1病毒基因亚型均以CRF01_AE为主,且呈上升趋势。结论江苏省HIV感染者抗病毒治疗失败人群HIV-1基因型耐药率有上升趋势,应加强对抗病毒治疗患者的耐药检测,从而及时合理调整抗病毒治疗方案。     

新疆和田地区新近诊断HIV-1人群耐药传播及亚型分布情况调查

目的了解新疆和田地区未治疗的HIV-1新诊断人群耐药传播情况及亚型分布。方法对新疆和田地区2013~2014年新诊断HIV-1感染人群随机抽样,对样本HIV-1 POL区进行亚型及耐药基因型分析,并评估新诊断人群HIV-1耐药传播水平。结果共有203个样本获得有效序列,样本中07_BC重组亚型193人,比例最大,占95.07%;C亚型5人,占2.46%;01_AE/B亚型2人,08_BC亚型3人;对HIV-1 POL区耐药基因突变位点进行分析,PR区耐药传播率为0.99%;RT区耐药传播率为2.46%。HIV-1耐药总传播率低于5%。结论新疆和田地区HIV-1新诊断人群的亚型主要是以07_BC重组亚型为主;和田地区未经抗病毒治疗新诊断HIV-I感染者中已经出现PR和RT区耐药突变株,但传播水平尚处于低流行状态,应适时开展耐药性监测。     

凉山彝族自治州HIV/AIDS抗病毒治疗前HIV-1耐药情况及其影响因素分析

目的 了解凉山彝族自治州（凉山州）HIV/AIDS抗病毒治疗前HIV-1耐药情况及其影响因素,为预防HIV-1耐药毒株的传播提供参考依据。方法 分别于2017年1月1日至6月30日、2018年1月1日至6月30日在凉山州开展HIV/AIDS抗病毒治疗前HIV-1耐药的横断面调查。提取获得HIV-1 pol基因区序列,根据2014年WHO耐药监测指南的推荐标准,应用HyPhy 2.2.4和Cytoscape 3.6.1软件进行HIV-1耐药毒株传播网络分析。结果 研究对象464例HIV/AIDS,HIV-1毒株为CRF07_BC亚型的占88.6%（411/464）,总的HIV-1耐药率为9.9%（46/464）,非核苷类反转录酶抑制剂（NNRTI）、核苷类反转录酶抑制剂（NRTI）和蛋白酶抑制剂（PI）耐药率分别为6.7%（31/464）、1.9%（9/464）和0.4%（2/464）;有1组HIV-1新型重组毒株URF_01BC亚型独立成簇并携带相关耐药突变位点;多因素logistic回归分析结果显示,与异性性传播人群相比,注射吸毒人群的HIV-1耐药风险较高（aOR=3.03,95% CI：1.40～6.54）。结论 凉山州HIV/AIDS抗病毒治疗前的HIV-1耐药率较高,且有新型重组毒株URF_01BC亚型携带相关耐药突变位点的成簇传播,建议加强HIV-1耐药毒株传播的预防工作。     

云南省德宏州2009年HIV-1耐药株传播水平调查

抗反转录治疗(ART)在降低HIV-1感染者并发症和艾滋病患者死亡率的同时,也促进了HIV-1耐药株的发生.耐药株有可能传播到新感染人群,从而使尚未开始治疗的HIV感染者携带HIV耐药株,导致以后的抗病毒治疗产生困难.本研究于2009年在云南省德宏州开展了HIV-1耐药警戒线调查.     

宁夏HIV-1感染者原发性耐药及基因变异型研究

目的 掌握本地区HIV-1 病毒耐药毒株的流行与传播情况,为有效的抗病毒治疗提供参考依据。方法 2018年3月1日-6月30日在宁夏开展HIV/AIDS抗病毒治疗前HIV-1耐药的横断面调查。提取获得HIV-1 pol基因区序列,根据2015年WHO耐药监测指南的推荐标准,采用Shafer 的耐药性突变积分表耐药评分,分值≥15判为耐药。结果 调查68例HIV/AIDS,58例巢式PCR检测获得HIV-1病毒pol区基因序列。年龄中位数为36.5岁（IQR:30～50）;男性55例(94.8%),女性3例(5.2%), Shafer 的耐药性突变积分表耐药评分,7例判为耐药,耐药率12.1%。存在4种基因亚型,分别是B亚型、CRF01_AE 亚型、CRF07_BC亚型和CRF55_01B亚型。结论 宁夏HIV-1原发性耐药率处于较高水平,应继续加强艾滋病抗病毒治疗前耐药监测。     

台州市2016-2018年新报告HIV/AIDS抗病毒治疗前HIV-1耐药及亚型流行特征分析

目的 了解台州市新报告HIV/AIDS抗病毒治疗（ART）前HIV-1耐药情况及亚型流行特点。方法 于2016年1月至2018年12月在台州市开展新报告HIV/AIDS在ART前HIV-1耐药的横断面调查,RT-PCR扩增获得HIV-1 pol基因片段并测序,提交序列至斯坦福大学耐药数据库,根据2014年WHO耐药监测指南的推荐标准,确定耐药突变位点以及HIV-1毒株对抗病毒药物的敏感性。结果 2016-2018年台州市新报告HIV/AIDS中成功获得HIV-1 pol基因区序列的研究对象806例,ART前HIV-1耐药率为2.9%（23/806）,其中,非核苷类反转录酶抑制剂（NNRTIs）、核苷类反转录酶抑制剂（NRTIs）和蛋白酶抑制剂（PIs）耐药率分别为1.9%（15/806）、0.6%（5/806）和0.0%。2016-2018年新报告HIV/AIDS在ART前HIV-1耐药率依次分别为1.6%、1.8%和4.8%。NNRTIs和NRTIs耐药突变位点以K103 N（0.7%）和M184I/V（0.5%）为主。HIV-1亚型以CRF01_AE（42.7%,344/806）、CRF07_BC（28.9%,233/806）和CRF08_BC（11.2%,90/806）为主。同性性传播者HIV-1亚型以CRF01_AE（53.3%,136/255）和CRF07_BC（32.2%,82/255）为主;异性性传播者HIV-1亚型以CRF01_AE（37.7%,203/539）、CRF07_BC（27.5%,148/539）和CRF08_BC（16.1%,87/539）为主。结论 2016-2018年台州市新报告HIV/AIDS在ART前HIV-1耐药率处于低流行状态,但存在上升趋势,需加强对HIV-1耐药型毒株的监测工作。     

云南省德宏州HIV-1新近感染者基因型耐药分析

目的 了解云南省德宏州HIV-1新近感染者中耐药的发生情况.方法 收集德宏州2006年7-12月期间所有的HIV-1阳性样品共1048份,使用BED捕获酶免疫试验进行新近感染检测,共检出新近感染样品101份;使用Bayer公司的TruGene方法进行基因型耐药检测,应用所有样品的序列构建系统进化树以确定样品的亚型.结果云南省德宏州HIV.1新近感染者巾的耐药发生率为6.25%(4/64),样品PR区中M36I/V、L63P和H69K等次要耐药突变出现的频率较高,分别占81.25%、70.31%和65.63%;HIV-1流行株以C/CRF07 BC/08_BC为主,占65.63%(42/64).结论德宏州HIV-1新近感染者中耐药的流行处于中等水平;有必要加强HIV-1的耐药监测.     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.     

Psychopathological features of a patient population of targets of workplace bullying

BACKGROUND: A strong association between workplace bullying and subsequent anxiety and depression, indicated by empirical research, suggests that bullying is an aetiological factor for mental health problems. AIMS: To evaluate levels of stress and anxiety-depression disorder developed by targets of workplace bullying together with outcome at 12 months and to characterize this population in terms of psychopathology and sociodemographic features. METHODS: Forty-eight patients (36 women and 12 men) meeting Leymann Inventory of Psychological Terror criteria for bullying were included in a prospective study. Evaluations were performed at first consultation and at 12 months using a standard clinical interview, a visual analogue scale of stress, the Hospital Anxiety and Depression (HAD) scale, the Beech scale of stress in the workplace and a projective test (Picture-Frustration Study). RESULTS: At first consultation, 81% of patients showed high levels of perceived stress at work and 83 and 52% presented with anxiety or depression, respectively. At 12 months, only 19% of working patients expressed a feeling of stress at work. There was a significant change in symptoms of anxiety while there was no change in symptoms of depression. Stress at work and depression influenced significatively capacity to go back to work. At 12-month assessments, workers showed a significantly better score on the HAD scale than non-workers. Over half the targets presented a neuroticism-related predominant personality trait. CONCLUSION: Workplace bullying can have severe mental health repercussions, triggering serious and persistent underlying disorders.     

The rise and fall in incidence of malignant mesothelioma from a British Naval Dockyard, 1979-1999

BACKGROUND: The incidence of malignant mesothelioma in Britain is predicted to rise over the next 15-25 years because of past failure to protect the workforce against inhalation of asbestos. In British Naval dockyards, alternative insulation materials and respiratory protection were introduced from the mid-1960s. Aims This study was carried out to investigate the effects of these control measures on mesothelioma deaths in dockyard workers. METHODS: Cases of mesothelioma of the pleura and peritoneum between 1979 and 1999 in workers from the Devonport Naval Dockyard, south-west England, were sought from coroners' and medico-legal records. RESULTS: Three hundred and one cases were identified, 7% peritoneal. The peak incidence occurred in 1991 with 25 cases per annum (quadratic model fit R(2) = 74.2%, P < 0.001) and we predict that by 2003 the incidence will fall to fewer than five cases per annum. The mean time between first exposure and presentation was 48.5 years [95% confidence interval (CI) = 47.3-49.8], but this was significantly shorter in the more heavily exposed trades, when compared with the less heavily exposed (42 years, 95% CI = 39.0-45.0, versus 49.5 years, 95% CI = 48.2-50.9). Those with higher exposure were also at significantly greater risk of peritoneal disease (P < 0.023, Fisher's exact test). CONCLUSION: The reduction in incidence of mesothelioma is greater than can be accounted for by reduction in numbers of dockyard workers over the last 50 years. Changes in insulation materials and improved industrial hygiene measures introduced into the Devonport Dockyard from the mid-1960s have resulted in an earlier decline in the incidence of malignant mesothelioma than that predicted for the British workforce as a whole.     

Organophosphate toxicity and occupational exposure

The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.     

Miliaria rubra of the lower limbs in underground miners

This report documents a case series of miliaria rubra of the lower limbs in miners at a deep underground metalliferous mine in tropical arid Australia. During the summer months of February and March 1999, all cases of miliaria rubra of the lower limbs in underground miners seen at the mine's medical centre were clinically examined and administered a questionnaire. Twenty-five patients were seen, an incidence of 56.4 cases per million man-hours. Miliaria rubra was most often located between the ankle and knee (88% of cases). Twenty-four percent had concurrent folliculitis and 20% had concurrent tinea. Thirty-two percent had a personal history of asthma. Walking through ground-water and splashing of the legs was common. Three to 4 weeks of sedentary duties in air conditioning was generally required to achieve resolution of miliaria rubra. The incidence of miliaria rubra of the lower limbs is 38% of the incidence of heat exhaustion at the same mine. The length of disablement is greater, however. Atopics may be at increased risk of miliaria rubra. Control measures are discussed.     

Planning research

The starting point for any research project should be a question.Once this has been defined and the relevant scientific literaturereviewed, a protocol should be drawn up. This will be used notonly as a guide to the conduct of the study and in the preparationof the final report, but also in seeking any financial supportand approvals that are required for the investigation. A protocolis normally arranged in sections covering the background tothe study, the question(s) that it will address, the methodsthat will be used for the collection and analysis of data, thestatistical power of the investigation (where relevant), anyethical considerations, and the financial input that will beneeded. A pilot study is often helpful where aspects of thestudy method are untried or of uncertainvalidity.     

Stress in the Norwegian police service

BACKGROUND: High levels of stress have been attributed to the conditions of police work, but there is little empirical evidence for this. AIMS: To develop a new instrument to measure job stress in the police; to assess the most severe and frequent police stressors; to compare levels of stress according to the demographic and organizational factors; and to study stress in relation to personality traits, work locus of control and coping strategies. METHODS: A comprehensive nationwide questionnaire survey of 3272 Norwegian police at all hierarchical levels, including the Norwegian Police Stress Survey (NPSS), the Job Stress Survey, the Basic Character Inventory, the Work Locus of Control Scale, and the Coping Strategies Scale. RESULTS: Work injuries were appraised as the most stressful but least frequent stressor and job pressure was reported the least severe but most frequent stressor. Females experienced job stressors less frequently, but appraised them as more severe than men did. Older police officers reported more job pressure severity and fewer work injuries. The police in districts where peer support was planned but not implemented, and who worked in districts with more than 50,000 inhabitants, perceived the lack of support more severely than others. The correlations between stress and personality traits, work locus of control, and coping were moderate. CONCLUSIONS: The NPSS captures police-specific stressors that are not adequately measured by global stress instruments. The study of stress in police work should preferably involve a nationwide use of police-specific stress instruments.