HIV-1基因亚型变化与贵州省艾滋病流行特征分析

目的:研究贵州省HIV-1亚型变化与艾滋病流行特征的关系.方法:分3个时段检测贵州省多个地区190份HIV样本,用套式PCR扩增其env基因片段并测序分析,将实验结果与贵州省艾滋病流行特征进行相关分析.结果:1998年检出B、C/CRF07_BC/CRF08_BC和CRF01_AE 3种HIV-1毒株,此间艾滋病流行以B和C/CRF07_BC/CRF08_BC毒株为主,主要经血液途径传播(占86.4％);2002年检出毒株均为C/CRF07_BC/CRF08_BC亚型毒株,这一时段艾滋病流行以吸毒传播为主(占100％);2007年检出B、CRF01_AE、C/CRF07_BC/CRF08_BC等3种亚型毒株,以CRF01_AE毒株为主(占52.1％),主要经性传播.结论:贵州HIV流行毒株随时间和传播途径变化而发生变化;目前主要流行毒株为CRF01_AE亚型毒株,主要在性接触人群中传播;对HIV-1基因亚型进行及时监测,能够预测艾滋病的流行特征.     

江苏省HIV-1流行株env和pol基因亚型及其系统分析

目的:了解江苏省HIV-1流行株env和pol基因亚型及其系统.方法:收集42份血清抗-HIV阳性者的血浆标本并提取RNA,逆转录为模版DNA后采用巢式 PCR法扩增env及 pol基因,对扩增产物进行核苷酸序列测定,比对确定基因亚型,分析不同途径感染者的基因亚型,构建系统进化树.结果:42份标本中,扩增出env及pol基因片段27份(64%);共发现5种 HIV-1亚型,其中 CRF01-AE亚型 19份、C亚型 2份、B亚型3份、CRF08-BC 2份、G亚型1份.经静脉药瘾感染者基因型多为CRF01-AE亚型;经性接触感染者HIV-1基因亚型包括检出的全部亚型,经性接触及吸毒感染者基因亚型均为CRF01-AE亚型.两基因构建系统进化树高度一致,主要有CRF-01AE、B-07、G、C和CRF-08BC 5种HIV亚型在流行,而以CRF-01AE为主要流行株.结论:江苏省 HIV-1基因亚型至少有5种,其中 CRF01-AE为主要亚型.     

HIV-1亚型的测定方法及分型的意义

人类获得性免疫缺陷病病毒(HIV)的基因具有高度变异性,在流行过程中发生变异,形成多种具有相对独立性的基因亚型。近年来,国内外学者就HIV各亚型的流行情况及HIV亚型与HIV疫苗研制的关系等做了很多工作。本文对HIV基因分型的方法及开展HIV亚型调查的意义作一综述。     

广州市孕产妇人群HIV-1亚型分布和耐药特征分析

目的 了解广州市孕产妇人群艾滋病病毒1型（HIV-1）亚型和耐药情况。 方法 收集广州市2009 — 2014年孕产妇人群HIV-1抗体阳性样本,扩增蛋白酶（PR）和反转录酶（RT）基因序列,测序后构建系统进化树确定亚型,并与斯坦福大学HIV耐药数据库比对进行耐药分析。 结果 成功获得178份基因片段,其中10份为外籍病例;中国籍病例以CRF01_AE ［42.86%（72/168）］ 和CRF07_BC ［31.55%（53/168）］为主,外籍病例以C和CRF01_AE为主,各占30.00%（3/10）。 中、外籍病例的亚型分布差异有统计学意义（P＜0.001）。 样本总体耐药突变率为12.36%（22/178）,低度以上耐药率为5.62%（10/178）,蛋白酶抑制剂（PIs）、核苷酸反转录酶抑制剂（NRTIs）和非核苷酸反转录酶抑制剂（NNRTIs）耐药率分别为2.81%（5/178）、1.12%（2/178）和2.25%（4/178）。 耐药突变率最高的亚型为C亚型［50.00%（3/6）］。 5例外籍病例携带耐药突变,其中3例为耐药病例。 3.37%（6/178）样本被预测对单类药物呈高度耐药,未发现对多类药物呈高度耐药的样本。 结论 广州市HIV感染的孕产妇人群中有12种病毒亚型,以CRF01_AE和CRF07_BC为主,耐药突变率及耐药率低,但存在PIs或NRTIs或NNRTIs的高度耐药毒株且外籍病例具有较高耐药突变率和耐药率。      

上海地区HIV-1感染者耐药基因型检测及亚型分析

目的研究上海地区人类免疫缺陷病毒（H IV）感染者/获得性免疫缺陷综合征（AIDS）患者耐药性基因型以及亚型的分布情况。方法采用美国拜耳公司H IV耐药检测试剂盒（TRUGENE（H IV-1 Genotyp ingK it）,扩增H IV-1靶序列（pol基因）中长度分别为297bp的蛋白酶基因片段和621bp的逆转录酶基因片段,OpenGene（DNA测序系统和数据分析软件进行测序和序列分析,利用H IV Database网站提供的H IV基因亚型分析软件（BLAST）对所得到的靶序列进行亚型分析。结果对87例H IV/AIDS患者的病毒载量和CD4＋T淋巴细胞计数4年随访中,其中61例接受高效抗逆转录病毒联合治疗（HARRT）的患者中,有4例性传播患者检测结果显示出现逆转录酶类耐药相关位点,49例合并血友病的患者,服药的依从性好,病毒载量检测均低于检测限（？50拷贝/mL）。10例未接受过HARRT治疗的患者标本中未检出耐药相关突变。对16份标本进行亚型分析,发现1例国内尚未见报道的ADHK重组型。结论利用TRUGENE（H IV-1系统,进行H IV-1耐药性基因型的检测,可以有效地监测接受HARRT治疗前后患者血浆H IV-1的耐药情况,并对不同的亚型进行分析。     

世界新兴城市对疫苗接种带来巨大挑战——联合国儿童基金会

正联合国儿童基金会免疫接种负责人表示,随着城市的迅猛发展,给世界最贫困儿童接种疫苗带来巨大挑战,同时增加疾病传播、暴发流行的危险性。在城市贫民区,疫苗接种覆盖面有限,其中越来越多的儿童未能接种疫苗。联合国儿童基金会首席顾问兼免疫接种主要负责人Robin Nancy表示,"我们特别担心疾病在城市中暴发流行,因为这可能快速传播并影响很多人"。据联合国估计,到2030年,主要在亚非地区,平均每4人中就有1人生活在城市贫民区或者     

1例复杂重组HIV-1亚型(CRF09-cpx)的鉴定

目的鉴定我国首例报道的复杂重组HIV-1（CRF09-cpx）感染病例，回顾性观察其抗病毒治疗的效果及耐药性的产生。方法分别采用蛋白酶基因、反转录酶基因以及env基因片段进行HIV-1的亚型分析；采用Trugene HIV-1基因型检测系统进行HIV-1基因型耐药检测。结果患者所感染的毒株与CRF09复杂重组毒株亲缘关系最为密切；在治疗过程中出现了耐药相关的位点突变并导致对多种药物产生耐受，同时表现出了耐药位点的累积。结论鉴定了我国首例报道的CRF09复杂重组HIV-1毒株并初步分析其耐药特征。     

云南省2006年HIV-1流行毒株的基因测定

目的 为了研究在中国云南流行的艾滋病毒I型(HIV=1)流行毒株的亚型类型与变异特征,进行分子流行病学研究,为艾滋病预防控制工作提供参考.方法 血浆来源于云南省监测系统中的19例HIV-1感染者.采用逆转录聚合酶链反应(RT-PCR)法,从19例患者血清中扩增HIV-1pol-gag共同拥有区片段并直接进行序列测定,所得序列用BioEdit和Mega软件进行亚型及系统发生树分析.结果 19例标本结果显示,12例为CRF08-BC、3例为CRF07-BC、1例为B型、3例为CRF01-AE型.19例毒株间的基因离散率都比较小,CRF08-BC亚型毒株间的基因离散率为2.45%,CRF07-BE亚型毒株间的基因离散率为2.16%;B亚型毒株为5.00%;CRF01-AE亚型毒株与来自泰国的流行CRF01-AE毒株AB032741、U51189的基因离散率分别为3.12%、3.22%.结论 上述结果表明,云南地区CRF-BC重组亚型已成为HIV-1流行病学优势亚型,结果基本上反映了我国HIV-1分子流行病学现状.     

中国HIV-1流行毒株的耐药基因变异研究现状

HIV耐药性的产生可能是病毒自发突变和药物压力选择的结果,但已成为维持高效抗逆转录病毒疗法(Highly active antiretroviral therapy,HAART)长期疗效的主要障碍.耐药病毒的出现促进了耐药检测方法的发展,而耐药检测的目的 在于帮助医师根据患者的个体状况选择最合适的有效治疗方法.目前,中国HIV-1流行毒株的耐药产生现状不容乐观.     

云南省2006年HIV-1流行毒株的基因测定

目的为了研究在中国云南流行的艾滋病毒Ⅰ型（HIV-1）流行毒株的亚型类型与变异特征，进行分子流行病学研究，为艾滋病预防控制工作提供参考。方法血浆来源于云南省监测系统中的19例HIV-1感染者。采用逆转录聚合酶链反应（RT—PCR）法，从19例患者血清中扩增HIV-1pol—gag共同拥有区片段并直接进行序列测定，所得序列用BioEdit和Mega软件进行亚型及系统发生树分析。结果19例标本结果显示，12例为CRF08-BC、3例为CRF07-BC、1例为B型、3例为CRF01-AE型。19例毒株间的基因离散率都比较小，CRF08-BC亚型毒株间的基因离散率为2．45％，CRF07-BC亚型毒株间的基因离散率为2．16％；B亚型毒株为5．00%；CRF0-1AE亚型毒株与来自泰国的流行CRF01-AE毒株AB032741、U51189的基因离散率分别为3．12％、3．22％。结论上述结果表明，云南地区CRF—BC重组亚型已成为HIV-1流行病学优势亚型，结果基本上反映了我国HIV-1分子流行病学现状。     

HIV-1 RNA levels in the cerebrospinal fluid may increase owing to damage to the blood-brain barrier

Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is not yet known which factors influence the amount of HIV-1 in the CSF, either qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from 24 HIV-infected patients using zidovudine who underwent lumbar puncture in order to establish a diagnosis for a neurological disorder. Several factors were examined for possible correlation with the amount of HIV-1 RNA in the CSF: age, gender, the medical indication for lumbar puncture, the most recent CD4 cell count in blood, zidovudine dose, duration of treatment with zidovudine, the zidovudine concentration in plasma and CSF, and the total protein concentration in plasma and CSF. The only statistically significant factor was the total protein level in the CSF, which showed a positive relation with the amount of HIV-1 RNA in the CSF. This study indicates that increased levels of HIV-1 RNA in the CSF of neurologically symptomatic patients are the result of damage to the blood-brain barrier.     

New therapy to revert dysfunctional antibody responses during HIV-1 infection

Individuals infected with HIV-1 progress to AIDS at different rates. Rapid progressors develop AIDS within 2-5 years of initial infection, compared with approximately 10 years in typical progressors. Progression to AIDS is associated with impaired humoral and cellular immunity. In this issue of the JCI, Titanji and colleagues report that activated memory B (mBAct) cells are depleted in SIV-infected macaques defined as rapid progressors. Depletion was mediated by programmed death-1 (PD-1) and resulted in reduction of antibody titers specific for SIV and bacterial antigens. Interestingly, blockade of PD-1 in infected animals protected B cells from apoptosis and increased levels of SIV-specific antibodies in blood. These findings pave the way for a new therapeutic strategy aimed at improving humoral immunity in HIV-1 infection.     

New HIV-1 protease inhibitors in development

Protease inhibitors block the protease enzyme of HIV-1. When new viral particles break off from an infected cell, protease cuts long protein strands into the parts needed to assemble a mature virus. When protease is blocked, the new viral particles cannot mature. Protease inhibitors being tested in humans include Atazanavir, GW433908, L-756,423, Mozenavir(DMP-450), Tipranavir and more. Several firms are trying to develop a new type of protease inhibitor that will be the more favorable pharmacokinetic and resistance profiles compared with currently available drugs. We cannot expect that every one of the drugs listed in this paper will be successfully developed. However, it is likely that significant clinical advancements can be made with those that are proven to be active and safe for patients in need.     

HIV-1 infection and the kidney: an evolving challenge in HIV medicine

With the advent of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has declined substantially, and cardiovascular, liver, and renal diseases have emerged as major causes of morbidity and mortality in individuals with human immunodeficiency virus (HIV). Acute renal failure is common in HIV-infected patients and is associated with acute infection and medication-related nephrotoxicity. HIV-associated nephropathy is the most common cause of chronic kidney disease in HIV-positive African American populations and may respond to HAART. Other important HIV-associated renal diseases include HIV immune complex kidney diseases and thrombotic microangiopathy. The increasing importance of non-HIV-associated diseases, such as diabetes mellitus, hypertension, and vascular disease, to the burden of chronic kidney disease has been recognized, focusing attention on prevention and control of these diseases in HIV-positive individuals. HIV-positive individuals who experience progression to end-stage renal disease and who have undetectable HIV-1 viral loads while receiving HAART should be evaluated for renal transplant. Emerging evidence suggests that HIV-positive individuals may have graft and patient survival comparable to HIV-negative individuals. Several studies suggest that HIV-1 can potentially infect renal cells, and HIV transgenic mice have clarified the roles of a number of HIV proteins in the pathogenesis of HIV-associated renal disease. Host factors may modify disease expression at the level of cytokine networks and the renal microvasculature and contribute to the pathogenic effects of HIV-1 infection on the kidney.     

Antibody responses to HIV-1 antigens are higher in HIV-1(+) intravenous drug users than in HIV-1(+) homosexuals.

Immune responses to HIV-1 infection of 42 HIV-1-positive asymptomatic intravenous drug users (IVDUs) were compared with those of 135 HIV-1-infected asymptomatic homosexual men in the present study. Twenty-five HIV-1(-) individuals served as normal controls. The comparison included antibody responses to five computer-predicted epitopes of HIV-1 p17, and viral proteins gp120 and p24 as well as p17. Major immunophenotypes were also investigated. Results showed that antibody responses to the five epitopes were significantly higher in the IVDUs. A larger proportion of the IVDUs, with respect to that of homosexuals, showed positive antibody responses to p24 and p17, respectively. However, the antibody response to gp120 was similar between the two cohorts. Immunophenotyping showed that HIV-1(+) homosexuals had higher profiles in most of the major subsets than did the IVDUs, especially in the total count of lymphocytes, absolute numbers of CD3+ cells and CD8+ cells. It appeared that the HIV-1(+) IVDU cohort had higher antibody responses to most of the viral antigens, but had lower levels of lymphocyte subsets in comparison with HIV(+) homosexuals.     

HIV-1病毒载量测定技术的新进展

HIV-1病毒载量是指机体内游离病毒的含量.它是一个计数单位,表示每毫升血浆中含多少拷贝数的HIV-1RNA,是反映HIV-1患者疾病进展的关键指标之一[1].通过对HIV-1病毒载量的测定,不仅可以帮助判断HIV-1感染者的状况,还可以用于判断抗病毒治疗的效果,当患者出现耐药性时,也能很快地给出结果从而指导治疗的优化[2].相对于CD4的测定,病毒载量的测定能够提供较早的参考信息.