北京市2006年新确认HIV-1感染者耐药突变的流行性研究

目的 研究北京市2006年新确认HIV-1感染者毒株的耐药突变本底数据.方法 随机选取北京市2006年新确认HIV-1感染者抗凝全血标本50份,提取血浆病毒RNA,用逆转录聚合酶链反应扩增HIV-1 pol区基因片段,并进行序列测定及耐药基因型分析.结果 成功扩增出34份标本的pol区基因;在1例样本的蛋白酶编码区检测出1个主要耐药突变,7例样本检测出7个次要耐药突变,主要耐药突变为M46L,毒株是CRF01_AE亚型,次要耐药突变有4种,出现的频率分别为A71T(2个)、A71V(3个)、Q58E(1个)、V11IV(1个).在14例样本逆转录酶编码区检测出一种或多种核苷类和(或)非核苷类逆转录酶抑制剂耐药突变,9例标本检出核苷类逆转录酶抑制剂耐药突变,出现频率分别为:V118I(42.9%)、M184V(7.1%)、A62V(7.1%)、K70T(7.1%)、K65R(7.1%)、K219N(7.1%)、T69d(7.1%)、V75LV(7.1%)、K219R(7.1%);10例标本检出核苷类逆转录酶抑制剂耐药突变,出现的频率分别为V1061(35.5%)、Y181C(15.4%)、K103KR(7.7%)、K103R(7.7%)、L100LV(7.7%)、V1081(7.7%)、V179D(7.7%)、V179DV(7.7%).结论 北京市2006年新确认HIV-1感染者毒株中已经存在一定比例耐药突变,有必要定期进行耐药性监测研究.     

杭州市2020—2022年新报告HIV/AIDS人群病毒基因亚型及治疗前耐药分析

目的了解杭州市新报告HIV感染者/艾滋病患者(HIV/AIDS)抗逆转录病毒治疗(ART)前HIV-1亚型流行特征及耐药情况。方法收集杭州市2020—2022年新确证且未经抗病毒治疗的HIV/AIDS病例血样, 扩增HIV-1pol区基因并测序。使用MEGA7.0软件构建系统进化树判断亚型, 提交序列至斯坦福大学耐药数据库, 确定耐药突变位点及毒株对药物的敏感性。结果获得2 700条pol基因序列, 发现12种HIV-1亚型, 以CRF07_BC (46.8%, 1 263/2 700)和CRF01_AE (34.6%, 933/2 700)为主。ART前HIV-1耐药率8.1%(220/2 700), 其中, 蛋白酶抑制剂(PIs)、核苷类反转录酶抑制剂(NRTIs)和非核苷类反转录酶抑制剂(NNRTIs)耐药率分别为2.8%(75/2 700)、1.3%(36/2 700)和4.4%(119/2 700)。220例耐药病例中, PIs耐药突变位点为Q58E(21.4%, 47/220), NRTIs耐药突变位点为M184V/I(5.9%, 1...     

我国HIV亚型研究进展

人类免疫缺陷病毒( human immunodeficiency virus,HIV)最显著的特点是其高度变异性,HIV在传播过程中产生了许多具有相对独立基因序列特征的组和亚型,对我国最为重要的是M (main)组,M组可以分为A～D、F～H、J和K这9个亚型[1]和若干流行重组型.亚型研究可以了解HIV流行毒株的种类、来源和流行时间,对了解HIV传播规律和流行趋势、指导艾滋病预防控制工作具有重要的意义.     

慢性乙型肝炎患者HBV耐药模式及rtA181变异准种分析

目的分析慢性乙型肝炎患者HBV逆转录酶区耐药变异情况及rtA181变异准种的分布。方法提取患者血清中HBVDNA,PCR扩增逆转录酶区域,产物测序后经软件比对分析耐药变异情况和基因型;对部分rtA181变异标本进行克隆后测序分析准种分布。结果 489例标本中,检出明确耐药变异265例,在B、C基因型中分布比例存在差异（56.6%vs43.0%,P=0.022）。拉米夫定相关耐药138例（52.1%）,以M204I、M204I/V＋L180M±L80I/V变异为主;阿德福韦相关耐药35例（13.2%）,以N236T＋A181T/V较为多见;拉米夫定＋阿德福韦相关耐药70例（26.4%）,几乎都和A181有关。rtA181准种分析发现1例位于同一病毒株的多耐药组合,且未发现单一A181T变异的病毒准种。结论 HBV耐药变异主要表现为M204和A181相关变异,耐药模式复杂;检测HBV逆转录酶区的变异有助于临床及时发现和确认耐药情况,指导临床合理进行抗病毒用药。     

抗HIV药物的新发展

随着高效联合抗逆转录病毒治疗(HAART)的进展,副作用、耐药性等问题日益突出,影响了持续治疗.目前正在研究许多新的药物,它们具有较小的毒副作用、更好的抗病毒及耐药毒株活性、服用方便等优点.本文阐述了正在开发中的核苷类逆转录酶抑制(NRTIs)、非核苷类逆转录酶抑制剂(NNRTIs)、蛋白酶抑制剂(Pis)及HIV病毒进入细胞抑制剂,阐述了它们的作用特点、使用剂量、剂型、抗病毒作用的活性及毒副作用,与其它抗病毒药物相互作用的研究.它们大多将会进入大规模临床研究,并可能获得批准而生产上市.     

HIV-1 CRF08BC亚型感染者治疗前耐药和多态性位点分析

目的了解我国HIV-1 CRF08_BC感染者治疗前耐药情况与基因多态性特征。方法采用横断面调查方法, 收集2018年全国治疗前耐药调查中的HIV感染者血浆样本, 提取RNA, 扩增蛋白酶和逆转录酶(PR/RT)区基因片段并测序, 利用HIVdb软件进行耐药判定, 使用χ2检验分析治疗前耐药与非耐药感染者氨基酸位点突变的差异, 利用CorMut R包分析耐药位点与多态性位点间突变共变异情况, 运用HIV-TRACE软件构建分子传播网络。结果共获得来自25个省市的465个CRF08_BC感染者的HIV序列, 总耐药率为17.8%(83/465), 非核苷类逆转录酶抑制剂(NNRTIs)、核苷类逆转录酶抑制剂(NRTIs)、蛋白酶类抑制剂(PIs)耐药率分别为16.6%(77/465)、1.1%(5/465)、0.9%(4/465), 其中利匹韦林(RPV)的耐药率最高(15.7%, 73/465)。位点E138A耐药突变的频率最高(11.6%, 54/465), 有6个多态性位点(S162C、K102Q、T200A、V179E、I202V、T200...     

山东省部分HIV-1流行株的亚型分析和序列特征研究

目的　对山东省HIV 1流行毒株进行亚型分析 ,并研究其变异特征。方法　采集 2 6份HIV 1感染者的外周静脉抗凝血 ,提取前病毒DNA进行体外扩增 ,获得包膜蛋白 (env)基因的核酸片段 ,并对其C2 V3及邻区的核苷酸进行测定和分析。结果　基因和氨基酸序列分析表明 ,2 6份标本中存在 4种亚型和重组毒株 (B′、C、A、A/E) ,其中B′ 17株 ,其组内基因距离为 11.6 9± 4 .19。V3环顶端四肽有 6种形式 ,最多的是GPGQ(15株 )、GPGR(6株 )。V3环第 11、2 5位氨基酸出现变异 ,并有 1株呈电荷双阳性。结论　山东省HIV 1流行株亚型较多 ,有重组毒株出现的可能 ,基因发生较大变异 ,HIV 1传播在山东省有加快的趋势。     

我国HIV-1主要流行株外膜蛋白(env)基因V3～V4区变异及其与生物学特性的关系

目的　研究我国HIV 1主要流行毒株亚型的envV3～V4区变异与生物学特性的关系。方法　应用nested PCR对 1 57份获自我国 1 2个省份的HIV 1毒株env区序列进行扩增 ,并使用ABI 377型测序仪测序 ,然后应用BLAST、GCG和MEGA等生物学软件或程序对env基因V3～V4区序列进行分析。结果　B′亚型毒株V3顶端四肽存在着 4种类型 :GPGR ( 54% )、GPGQ ( 2 8% )、GPGK( 1 6 % )和GPGA( 2 % ) ,B′/C重组毒株全部为GPGQ( 1 0 0 % ) ,CRF0 1 AE重组毒株呈现GPGQ( 95% )和GPGR( 5% )两种类型 ;B′/C和CRF0 1 AE重组毒株V3～V4区及其临近区域N 糖基化位点比B′亚型毒株N 糖基化位点保守。而B′亚型毒株V3环的净电荷分别显著高于B′/C和CRF0 1 AE毒株 (P <0 .0 1 ) ;根据V3环关键氨基酸推测辅助受体使用情况的结果显示 :B′亚型毒株有 9.2 6 %可能使用CCR5,7.4 1 %可能使用CXCR4 ,其余 83.33%不能对辅助受体的使用作出预测。所有B′/C重组毒株被预测可能使用CCR5。CRF0 1 AE重组毒株有 90 .4 8%被预测可能使用CCR5,没有被预测为使用CXCR4的序列 ,9.52 %不能作出预测。结论　B′亚型毒株大部分可能为NSI型 ,少部分可能为SI型 ,而B′/C和CRF0 1 AE重组毒株绝大部分为NSI型。我国主要流行株的V3～V4区尤其是V3环的氨基酸     

中国HIV-1型B、C亚型主要流行株外膜蛋白基因V3-V4区序列的变异分析

目的　研究我国人类免疫缺陷病毒 1型 (HIV 1)B、C亚型主要流行株在感染过程中基因变异的特点及其与选择压力的关系。方法　应用巢式聚合酶链反应 (nested PCR)对 2 5 8例HIV 1感染者血样中的HIV 1外膜蛋白 (env)基因进行扩增 ,并使用ABI 377型测序仪对扩增产物测序后 ,选择其中 37份B亚型和 35份C亚型HIV 1毒株env基因包括V3～V4区的序列进行比较分析 ,并计算和分析氨基酸同义替换与非同义替换的比值 (Ks Ka)。结果　B亚型毒株V3～V4区的基因离散率高于C亚型毒株。无论B亚型 ,还是C亚型毒株 ,其V4区基因序列较V3区变异更大。在C亚型毒株中 ,V3区基因序列变异甚至比V3上游区和C3区小。B和C亚型毒株整个V3～V4基因区的Ks Ka比值均 <1,差异有非常显著性 (P <0 0 0 1) ,其中B亚型毒株以V3区的Ks Ka比值最小 ,而C亚型毒株则以V4区的Ks Ka比值最小。结论　B和C亚型毒株env基因的变异主要发生在V4区而不是V3区。C亚型毒株V3区较V3上游区和C3区还要保守 ,是本研究的特殊发现。这两种亚型在我国快速流行中发生的变异是在选择压力下发生的 ,而不是随机进化的结果 ,而且选择压力对这两种亚型毒株V3、V4区的作用程度也不一样。这将为我国艾滋病防治策略的制定和疫苗研究提供科学的依据。     

Fighting HIV with HIV

This article presents a new possibility for therapy and treatment of human immunodeficiency virus infection.     

HIV antibodies for treatment of HIV infection

The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.     

Mechanisms of HIV persistence in HIV reservoirs

The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half‐life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut‐associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low‐level replication and persistent viremia during treatment. Latently, HIV‐infected CD4+ T cells harboring replication‐competent virus, HIV cell‐to‐cell spread, and HIV‐infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy.     

Overview of HIV

This article provides an overview and reviews the HIV pandemic, the basic biology and immunology of the virus (e.g., genetic diversity of HIV and the viral life cycle), the phases of disease progression, modes of HIV transmission, HIV testing, immune response to the infection, and current therapeutic strategies. HIV is occurring in epidemic proportions, especially in Sub-Saharan Africa. In the US, men who have sex with men account for over half of AIDS diagnoses; racial and ethnic minorities are disproportionally affected. Factors influencing the progression and severity of HIV infection include type of immune response, coinfection (e.g., another sexually transmitted infection, including hepatitis B or C), age and behavioral and psychosocial factors. Antiretroviral therapies can achieve reduction in blood levels of the HIV virus below the limits of detection by current technology. However, effective treatment requires adherence to therapy. Patient failure to adhere to treatment regimens results in detectible circulating virus and in HIV disease progression, and is the primary cause of drug resistance. In addition to research on the immunology and virology of the disease, other studies focus on behavioral and psychosocial factors that may affect medication adherence and risk behaviors.     

Role of HIV phenotypic assays in the management of HIV infection

Contemporary phenotypic assays such as the PhenoSense HIV assay are more straightforward to interpret than genotyping results because they do not require the expert interpretation of complex mutation patterns. The drug susceptibility data provides information for the clinician to select a treatment regimen effective against the predominant viral population circulating in the patient's blood. Compared to traditional phenotypic assays, the PhenoSense HIV assay uses a virus vector and a luciferase reporter gene to provide a quick and sensitive measure of viral replication. The main use of phenotypic assays at present is to identify those antiretroviral drugs that still retain activity against the patient's virus. Phenotypic assays are useful to provide guidance after treatment failure and to select a proper combination of drugs prior to initiation of therapy. They are also useful to detect transmission of resistance virus and to monitor HIV patients during early viral rebound. In essence, phenotypic testing provides information to target antiretroviral therapy against the predominant HIV variant in the patient for a prolonged suppression of viral replication, decreased mortality, and lower health-care costs.     

Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression

In this paper Zeda Rosenberg and Anthony Fauci review the prevailing hypotheses on the mechanisms by which human immunodeficiency virus (HIV) progressively and relentlessly destroys immune function in infected individuals. Although HIV can directly kill CD4+ T cells in vitro, the protracted course of HIV infection in vivo suggests that other pathogenic mechanisms are also involved. As a member of the lentivirus family, HIV can remain latent within the genome of the infected cell. Activation of HIV expression from a latent or low-level state of replication is dependent, in part, on the state of activation of the host cell. As a result, activation of HIV-infected CD4+ T cells or monocyte/macrophages during normal immune responses may ultimately result in the activation of HIV expression and spread of the infection. Thus, HIV may have developed the ability to use normal immune processes to its own reproductive advantage.