HIV drug resistance mutations following poor adherence in HIV‐infected patient: a case report

Acquired HIV drug resistance following poor adherence is common. We report a case of HIV‐infected patient with poor CD4 gain and self reported poor adherence. Investigations revealed high viral load and resistance to NRTIs and NNRTIs with sensitivity to boosted PIs. HIVDR mutations create treatment challenges in resource limited settings.     

太仓市慢性乙型肝炎患者耐药突变和基因型分布研究

目的：研究太仓地区慢性乙肝患者耐药突变和基因型分布情况,及 HBV 基因型与耐药突变的相关性。方法选择太仓地区350例慢性乙型肝炎患者,在使用核苷（酸）类药物抗病毒前,检测患者耐药突变及基因型情况,分析患者耐药突变与基因型的相关性。结果350例慢性乙肝患者,HBV 基因型分布：B 基因型172例,占49.14％;C 基因型164例,占46.85％;其中 D基因型9例,占2.57％;B、C 混合型基因型有5例,占1.42％;未发现其他基因型。本研究共检出58例耐药突变患者,其中 B 基因型22例,C 基因型35例,D 基因型1例,B、C 混合基因型患者未发现耐药突变。耐药突变位点：与拉米夫定相关的耐药突变36例（10.28％）,与阿德福韦相关的耐药突变16例（4.57％）,与恩替卡韦相关的耐药突变6例（1.71％）。结论太仓地区慢性乙肝患者 HBV 基因型以 B、C 型为主,2种基因型占90％以上,两种基因型比例相似。C 基因型患者发生耐药突变的比例较 B 基因型高,拉米夫定相关的耐药突变比例最高。建议对用药史不明确、复发再治疗的慢性乙肝患者,在接受核苷（酸）类药物治疗前进行耐药检测,选择针对性治疗方案。     

Update on antiretroviral treatment during primary HIV infection

Primary HIV-1 infection covers a period of around 12 weeks in which the virus disseminates from the initial site of infection into different tissues and organs. In this phase, viremia is very high and transmission of HIV is an important issue. Most guidelines recommend antiretroviral treatment in patients who are symptomatic, although the indication for treatment remains inconclusive in asymptomatic patients. In this article the authors review the main virological and immunological events during this early phase of infection, and discuss the arguments for and against antiretroviral treatment. Recommendations of different guidelines, the issue of the HIV transmission and transmission of resistance to antiretroviral drugs, as well as recently available information opening perspectives for functional cure in patients treated in very early steps of HIV infection are also discussed.     

Mechanism of HIV antiretroviral drugs progress toward drug resistance

The rapid replication rate of HIV-1 RNA and its inherent genetic variation have led to the production of many HIV-1 variants with decreased drug susceptibility. The capacity of HIV to develop drug resistance mutations is a major obstacle to long-term effective anti-HIV therapy. Incomplete suppression of viral replication with an initial drug regimen diminishes the clinical benefit to the patient and may promote the development of broader drug resistance that may cause subsequent treatment regimens to be ineffective. The increased clinical use of combination antiretroviral treatment for HIV-1 infection has led to the selection of viral strains resistant to multiple drugs, including strains resistant to all licensed nucleoside analog RT inhibitors and protease inhibitors. Therefore, it is important to understand the influence of such mutations on viral properties such as replicative fitness, fidelity, and mutation rates. Although research continues to improve our understanding of resistance, leading to refined treatment strategies and, in some cases, improved outcome, resistance to antiretroviral therapy remains a major cause of treatment failure among patients living with HIV-1.     

某地区乙型肝炎病毒基因型分布和P区耐药突变模式分析

目的探讨十堰地区乙型肝炎病毒(HBV)基因型分布和P区耐药突变模式及两者的相关性。方法将在该院进行治疗的224例慢性乙型肝炎患者纳入本研究,提取患者血液标本中的HBV DNA,利用ABI 3730型遗传分析仪对DNA进行测序,通过SeqMan软件实施序列比对,分析HBV DNA的基因型和P区耐药突变的情况。结果检出HBV基因型为B型者136例,占60.71%;为C型者62例,占27.68%。二者比例均高于D型、B+C型及未分型者,差异有统计学意义(P0.05)。78例明确出现耐药突变,其中B基因型对于拉米夫定以及阿德福韦的耐药率分别为18.38%与9.56%,与C基因型对于二者的耐药率16.13%与9.68%相比,差异均无统计学意义(P0.05)。B基因型患者M204V、M204I耐药突变的发生率分别为38.60%、17.54%,C基因型患者则分别为28.57%与38.10%,两种基因型患者比较差异无统计学意义(P0.05)。B、C型基因突变患者间YMDD突变(M204V、M204I)及非YMDD突变所占比例比较,差异均无统计学意义(P0.05)。B基因型及C基因型分别与M204V及M204I两种突变均呈正相关。结论十堰地区HBV的基因型主要是B型及C型,发生的HBV耐药突变则以M204I和M204V为主,在临床治疗时应按照基因分型以及耐药突变情况合理选择药物进行慢性乙型肝炎的治疗。     

HIV testing in 2006: issues and methods

Infection with HIV and subsequent development of AIDS is a pandemic. The Joint United Nations Program on HIV/AIDS together with the WHO and many relevant funding bodies demand that those infected should be reliably identified so that people who need, or will need, therapy may be provided for over time. This means that there is a renewed interest in testing for HIV and in laboratories’ performances and quality. Whatever the conditions under which testing is performed, and whatever the levels of training, the tests and their outcomes must exhibit equivalent, high standards of performance and reliable results. This is regardless of whether testing is conducted in the most sophisticated laboratories (either diagnostic or transfusion screening) to voluntary testing and counseling centers where those conducting testing may not be technically trained. This is not currently the case, especially in some places where HIV is most prevalent. To achieve uniformly high performance standards, quality assurance programs are imperative, but currently not sufficiently valued to be well supported with adequate funding or human resources. Accurate HIV testing is a cornerstone of blood safety, diagnosis of infection, patient management and surveillance.     

HIV testing in India

The National AIDS Control Organization (NACO) has initiated programs for HIV/AIDS control in India. Algorithms for HIV testing have been developed for India. NACO programs have resulted in HIV situation improving over the last decade.     

Beyond the end of exceptionalism: integrating HIV testing into routine medical care and HIV prevention

In September 2006, the US CDC issued new guidelines for HIV testing. These guidelines were designed not only to simplify and expand HIV testing but also to integrate testing into routine medical care in the USA. The nationwide implementation of these guidelines is currently facing several political and legal barriers. In this article, we examine the origins of current patient-driven and risk-based HIV testing in the USA and highlight shortcomings of this strategy. We then demonstrate how the changing HIV epidemic in the USA requires routine HIV screening at all points of contact in the medical system in order to control the HIV epidemic and how novel testing strategies could increase the yield of testing in these settings.     

Decision making in HIV testing among a group with low HIV risk

Relatively little is known about how individuals (apart from gay and bisexual men) decide to have an HIV test and how, once they have presented for testing, they make decisions about proceeding through the testing trajectory. This paper reports on a qualitative study in which 55 mainly heterosexual respondents with low HIV risk were interviewed about their experiences of decision making around HIV testing. Reasons for deciding to be tested centred on a desire for reassurance and the circumstances of the respondents' current relationship. The most common relationship reason focused on a desire to confirm HIV status before beginning sexual relations or engaging in unprotected sex with a partner. Although some respondents recognized that other individuals had influenced their decision to be tested, few said that pretest counselling had been influential in this respect. Instead, it was said to have promoted feelings of 'ownership' of a decision which had already been taken prior to counselling. The potential effects of HIV testing on HIV risk behaviour were also examined and a non-significant increase in unprotected sex was reported between the month before the test and the month after. The implications of these findings for the provision of HIV testing services are explored.     

Management of advanced HIV disease: resistance, antiretroviral brain penetration and malignancies

Data from Italy, Spain and the USA all highlight the worrying fact that presentation with advanced HIV disease – defined as a cluster of differentiation 4 (CD4) count <50 cells/mm³ or the presence of an acquired immunodeficiency syndrome‐defining illness – is increasingly common. A review from 2003 showed that 31% of patients in the UK and Ireland presented late (<200 CD4 cells/mm³). Early diagnosis is vital to ensure that patients benefit from antiretroviral therapy, and when patients present late, they do not obtain the benefits of early treatment. The risk of death is lower when antiretroviral therapy is initiated at CD4 counts of 201–350 cells/mm³ than at lower CD4 cell counts. In addition, the risk of unintentional infection of others is increased, which is particularly troubling in light of evidence that transmission of resistance can occur even in the absence of antiretroviral therapy. The management of patients with advanced disease and no complications is complex, but issues of transmitted resistance and comorbid conditions further confuse management decisions in the treatment of patients with higher CD4 counts. This article reviews recent evidence on transmitted resistance, the pharmacokinetics of antiretroviral drugs in patients with central nervous system disease and the management issues in patients with comorbid malignancies to offer practical advice on therapeutic options for treatment‐naïve patients who present with advanced HIV disease.     

HBV基因分型和耐药突变基因检测

目的探讨东营地区乙型肝炎病毒(HBV)基因型分布,乙型肝炎患者耐药情况,HBV基因型别与耐药以及突变位点关系。方法收集乙型肝炎患者血清300例,采用离心柱法提取HBV-DNA,聚合酶链反应(PCR)-反向点杂交法检测HBV分型和耐药突变。结果 300例HBV-DNA阳性患者中,检出B型、C型、B/C型及其他未检测出的基因型,未检出D型分型,检出结果中以C型为主,占81.8%;HBV患者耐药药物以拉米夫定和替比夫定的联合耐药为主,占43.6%;HBV耐药突变基因型主要为rt204I(24.35%)、rt204V(17.39%)及rt180M(17.39%);B型和C型的耐药突变率分别为30.77%和42.42%,差异有统计学意义(P0.05)。结论东营地区HBV基因C型多于B型,C型容易产生耐药,以rt204I,rt204V及rt180M基因突变型多见,拉米夫定和替比夫定的联合耐药多见,应根据基因分型和耐药突变结果对乙型肝炎患者选择适合的治疗方案。     

上海地区艾滋病病毒感染者/艾滋病患者原发性耐药基因调查及抗病毒治疗效果观察

目的 了解上海地区伴有HIV-1原发性耐药的艾滋病病毒感染者/艾滋病患者（HIV/AIDS）对高效抗反转录病毒治疗（HAART）效果的影响,评估长期抗病毒治疗方案,为调整治疗策略提供依据。方法 从上海市艾滋病治疗数据库中随机选取2007-2013年期间被诊断为HIV-1的感染者,在未治疗前进行原发性耐药检测。对其中原发性耐药的病例进行1~7年不等的随访检测,通过CD4+T淋巴细胞计数及病毒载量结果评估抗病毒治疗效果。结果 1 543例HIV-1感染者中发现HIV原发性耐药42例,其中失访8例,死亡1例,停药1例,最后获得32例原发性耐药者。32例中非核苷类反转录酶抑制剂（NNRTI）耐药相关突变11例,核苷类反转录酶抑制剂（NRTI）耐药相关突变7例,蛋白酶抑制剂（PI）耐药相关突变6例;对NRTIs和NNRTIs同时耐药突变有3例,同时发生对PIs和NNRTIs的耐药相关突变1例,同时发生对PIs和NRTIs的耐药相关突变2例;对整合酶抑制剂（IN）耐药相关突变2例,平均原发性耐药率为2.7%。随访监测CD4+T淋巴细胞计数和病毒载量变化结果显示,32例患者的CD4+T淋巴细胞数量在HAART治疗前和治疗后的0.5、1、2、3、4、5、6和7年（1个月）时分别为249.5157.4、304.9188.7、356.3206.4、441.4245.7、455.4256.8、453.2168.5、458.2202.4、454.066.8和432.0100.4个/l。服药依从性指标评估显示所有病例均每年检测病毒载量,除了2例病例病毒载量为600拷贝/ml和700拷贝/ml外,其余病毒载量检测均低于检测下限,病毒抑制率为100%。上述病例在随访期间,均因毒副反应而更换为其他一线药物或二线药物。结论 通过随访观察上海地区伴原发性耐药的HIV/AIDS对抗病毒的治疗效果,在原发性耐药率低的流行地区,如果治疗管理规范,患者服药依从性好,并经常开展公共卫生原发性耐药监测,在条件有限的情况下可不考虑进行治疗前原发性耐药检测。     

对护理人员HIV/AIDS有关知识和态度的调查分析

目的 了解护理人员掌握艾滋病的知识程度和态度,为实施相关的教育和培训提供依据.方法 采用问卷调查法对四川、云南和广西463例护理人员的艾滋病知识和态度进行调查.结果 三地护理人员的一般情况除是否参与艾滋病相关培训、专门针对护士的培训、所在医院是否有艾滋病患者外,其他各项差异有统计学意义(P＜0.05);护理人员艾滋病知识平均得分(12.95±2.35),三地间差异无统计学意义;护理人员对待艾滋病的一般态度得分(3.38±0.30),三地间差异无统计学意义(P＞0.05);在18项工作相关态度方面,超过80%的护理人员持认可度的条目有4条,三地护理人员间有6各方面的工作相关态度差异有统计学意义.结论 三地护理人员的艾滋病知识水平和不确定的态度不能满足艾滋病高流行势态的需求,尤以四川突出,为此加强三地护理人员有关艾滋病的培训迫在眉睫.     

颁布《全国艾滋病检测工作管理办法》的目的和意义

HIV感染的实验室检测是HIV感染者和AIDS患者的最基本诊断依据.但是,HIV检测不是单纯的业务项目,与其他传染病实验室检测项目不同,特别要求HIV检测的敏感度和特异度几近100%.如果其结果假阳性,会影响个人、家庭和社会的稳定,甚至导致受检者过激行为,有自杀举动;如果是假阴性,则会造成受检者不能及时接受医学干预,可以通过血液和性生活辗转传播,增加对社会的传染性.截至2007年底,全国已批准了HIV筛查实验室6 918家,确认实验室202家.为此卫生部正式颁布的<全国艾滋病检测工作管理办法>(下称办法),其目的 是使HIV检测工作走上法制化管理,是当前AIDS作为我国重点防治疾病的一项技术保障措施.本文还就<办法>发展和出台的过程,以及当前医院检验科要特别关注对<办法>执行过程中某些条款的理解,均作了简要说明.     

Use of rapid HIV antibody testing for controlling the HIV pandemic

The HIV pandemic continues to expand throughout Africa and southern Asia. Despite recent advances in therapy, the primary means of prevention continues to be the identification of infected patients through diagnostic testing, and the provision of counseling services to reduce HIV transmission. In order to facilitate the identification of infected patients, great strides have been made during the past 10 years towards the development of simple, rapid HIV antibody assays that require no specialized equipment, are relatively stable at ambient temperatures and can be easily performed by people who do not have a laboratory background. Evaluations of these assays have shown that when used in multiple assay algorithm strategies, they perform comparably with current laboratory-based methods. Effective global implementation of these tests will require a concerted effort from public and private health agencies, however, expanding the use of these assays can provide a significant opportunity to slow the devastating spread of HIV.     

医院获得性尿路感染大肠埃希菌ESBLs基因型与耐药性分析

目的了解医院获得性尿路感染大肠埃希菌(HA-UPEC)的耐药与超广谱β-内酰胺酶(ESBLs)基因型特征,指导尿路感染的临床用药与控制医院感染。方法收集住院患者尿路感染分离的168株大肠埃希菌,应用PCR扩增检测ESBLs主要基因型,分析这些菌株对常见16种抗菌药物的耐药特征。结果 168株HA-UPEC对复方磺胺甲噁唑、氨苄青霉素、头孢唑啉、头孢呋辛、头孢噻肟、头孢曲松、环丙沙星的耐药率高达70%以上。16种常见抗菌药物中,头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、丁胺卡那与亚胺培南的耐药率较低。与non-ESBLs大肠埃希菌相比,产ESBLs的大肠埃希菌对青霉素类、头孢菌素类、氟喹诺酮类的耐药率高。根据药敏谱,168株HAUPEC分为5个大组(A~E组),产ESBLs的大肠埃希菌主要分布在A、B、C组。CTX-M是主要的基因型(109株),其次是TEM(48株);59株产大于或等于2种ESBLs,3株未检测到ESBLs。耐药性聚类分组与ESBLs基因型关系分析发现,TEM在D组的分布率最高,为65.2%;SHV在C组未检测到,SHV在A组与B组间的分布不同;CTX-M在4个组的分布差异无统计学意义(P0.05),OXA在B组未检测到,OXA在A组与B组间的分布不同。结论产ESBLs大肠埃希菌的耐药情况比较严重,4种ESBLs基因型在不同组别的分布差异可能是产ESBLs的HA-UPEC耐药不同的原因之一,TEM基因型较敏感,CTX-M与SHV基因型较耐药;临床上应严格合理使用抗菌药物,及时掌握HA-UPEC ESBLs基因型与耐药性的变化,有利于减少多重耐药尿路感染大肠埃希菌的出现。     

基层护理人员对HIV/AIDS认识的调查分析

目的:为了解基层护理人员对HIV/AIDS的认识和接受态度,以便对护理人员实施有的放矢的继续教育。方法:2006年3月分层随机抽取田东县7所医院,向在职护士发放调查问卷150份,进行流行病学现况研究。结果:73.3%以上的护士对HIV/AIDS的基本知识掌握较好,但只有45.0%的护士能对病人作全程护理,其知识掌握与接受程度不成正比(P<0.05),特别是对自己患病态度6.7%的人采取自杀,说明护士对HIV/AIDS的恐惧心理严重。结论:医疗卫生部门应加强对基层护理人员关于HIV/AIDS知识的培训,加大宣传力度,提高护士思想认识,规范操作规程,尽可能减少医源性感染机会,同时政府部门应制定相应的政策以减轻护士的心理负担,从而达到“战胜艾滋”这一人类共同的目标。     

九江市浔阳区艾滋病高危人群行为与认知情况调查

目的了解九江市浔阳区艾滋病高危人群的分布、HIV感染情况和主要危险因素,为制定艾滋病防治措施提供依据,探索合适的健康教育和行为干预模式。方法采用方便抽样法抽取暗娼人群360人,采用方便抽样法和滚雪球法抽取吸毒人群360人,通过问卷调查有关行为因素。结果 360名暗娼艾滋病基本知识总体知晓率为75.2%,安全套使用率为67.8%,采集暗娼血样149份,未发现HIV抗体和梅毒抗体阳性。360名吸毒人群的艾滋病基本知识总体知晓率为83.7%,最近一个月66.9%的人注射过毒品,共针率为47.6%。吸毒人群安全套使用率偏低,采集吸毒人员血样198份,发现HIV抗体阳性1份,梅毒抗体阳性5份,HIV和梅毒感染率分别为0.51%和2.53%。结论艾滋病高危人群暗娼、吸毒人群存在感染HIV的诸多危险因素,应做好艾滋病的综合健康教育和行为干预工作,完善高危人群监测体系。     

Ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in KPC-producing Klebsiella pneumoniae infections: A case series

ObjectivesSince the introduction of the β-lactam/β-lactamase inhibitor ceftazidime-avibactam (CZA), rapid evolution of resistance has been reported in different KPC-producing Klebsiella pneumoniae isolates. In this multicenter retrospective study, we describe the emergence of CZA resistance and evaluate the mutations that might be responsible for the restoration of carbapenem susceptibility.MethodsDuring a study period of 18 months, KPC-producing K. pneumoniae isolates of five hospitalized patients were collected with phenotypic development of CZA resistance.ResultsIn vitro restoration of carbapenem susceptibility during treatment was observed in 3 isolates. Whole genome sequencing of these isolates showed a D179Y mutation in the KPC gene of 2 variants and a KPC-2 with a Δ242-GT-243 deletion (KPC-14). Two KPC-3 variants showed CZA resistance with sustained carbapenemase activity without genomic adaptations in the KPC gene.ConclusionsThis study confirms the emergence of CZA resistance in KPC K. pneumoniae. The role of carbapenems in treating patients with these variants is unclear and combination therapies warrant further investigation.