用CRISPR/Cas9系统消除潜伏的HIV前病毒基因组及其感染细胞的研究进展

艾滋病在全球采用联合抗逆转录病毒治疗后发病率及死亡率呈持续下降趋势,使之成为一种可管理的慢性传染病。但因受各种因素制约,艾滋病仍然是全球一个重要公共卫生问题。HIV/AIDS持续存在的主要原因是现有的治疗无法清除人体中存在的HIV潜伏库,由于这种库的存在,HIV/AIDS患者必须终生使用抗病毒药物来抑制病毒复制和反弹。成簇规律间隔短回文重复序列和相关核酸酶Cas9(CRISPR/Cas9)系统几年前以一种简单、快速及易操作的基因编辑技术问世,多项研究表明其在HIV感染的细胞和在动物模型实验中具有消除或破坏HIV储存库或HIV感染细胞的潜力,可能由此产生治愈HIV/AIDS的方法。本文分析了CRISPR/CAS9系统应用于消除潜伏HIV的结果,并对可能产生的问题和趋势进行了讨论。     

吸毒成瘾HIV/AIDS患者抗逆转录病毒治疗的初步探讨

目的 评价国产艾滋病抗病毒药物治疗吸毒成瘾艾滋病病毒感染者/病人(HIV/AIDS)的疗效及对治疗时机的探讨. 方法 采用回顾性研究方法,调查随访2004～2007年在北京佑安医院确诊并经抗病毒治疗的吸毒成瘾HIV/AIDS患者114例,按照疾病进展将随访对象分成艾滋病组( AIDS)和HIV感染组(free of AIDS) ,所有患者均用3种抗病毒药物(奈韦拉平 司他夫定 拉米夫定)治疗,疗程48周.常规方法检测患者治疗前后血CD4 T淋巴细胞数,核酸序列扩增技术(NASBA)测定病毒载量. 结果 114例吸毒成瘾HIV/AIDS患者CD4细胞数平均增加(182.39±90.70)个/mm3;其中35例吸毒成瘾HIV/AIDS患者中85.71%病毒载量下降至50 copies/ml以下, 下降2.5个Log数;艾滋病组与HIV感染组治疗后3、6、9和12个月CD4 T淋巴细胞差异有统计学意义(P＜0.05);治疗6个月后,HIV感染组病毒载量下降趋势较艾滋病组明显,但治疗12个月后 HIV感染组病毒载量较艾滋病组有反弹现象. 结论 吸毒成瘾HIV/AIDS患者选用国产艾滋病抗病毒药物奈韦拉平 司他夫定 拉米夫定治疗取得良好效果,并且对艾滋病患者的疗效好于HIV感染者.     

HIV-1潜伏感染及功能性治愈

尽管高效抗反转录病毒治疗(HAART)可有效控制艾滋病(AIDS)病人体内的艾滋病病毒1型(HIV-1)的复制,但却无法根除潜伏感染的病毒,这成为当前艾滋病治疗的主要难点之一。研究HIV-1在宿主细胞内建立和维持潜伏的分子细胞学机制,有助于发现新的抗病毒靶点和发展新的抗病毒治疗策略。近年来对HIV感染者/AIDS病人提出功能性治愈策略,相关的免疫或基因治疗手段被相继提出,部分策略已处于临床试验阶段。该文对HIV-1潜伏感染机制和功能性治愈相关研究进展进行简要综述。     

山东省608例HIV/AIDS病人抗病毒治疗结果分析

目的了解2003-2010年山东省接受艾滋病抗病毒治疗且目前仍在治疗的艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（HIV/AIDS病人）的治疗结果。方法收集2010年12月底前开始接受AIDS抗病毒治疗且目前仍在治的HIV/AIDS病人的随访资料,描述分析其一般情况,治疗前和治疗后不同时间段的CD4＋T淋巴细胞计数、病毒载量和机会性感染发生状况等。结果山东省2003-2010年接受AIDS抗病毒治疗且目前仍在治疗的HIV/AIDS病人608例,其中男性占65.6%（399/608）,女性占34.4%（209/608）,平均年龄为（40.2±10.2）岁,已婚或同居者占65.5%（398/608）;感染途径以异性性接触感染为主,占44.9%（273/608）,其次是同性性接触感染,占21.1%（128/608）;有182例更换了抗病毒治疗药物,占29.9%,换药主要原因为药物不良反应。基线时CD4＋T淋巴细胞平均计数≤200个/μL的占65.8%,200～350个/μL的占33.0%,≥350个/μL的占1.2%,同基线时相比,治疗前、治疗3个月、6个月、1年、2年、3年时CD4＋T淋巴细胞计数均有增加（P〈0.05）。治疗后病毒载量低于检出限的比例增高,机会性感染发生率降低。结论抗病毒治疗可有效提高HIV/AIDS病人的免疫力,有利于提高其生命质量。     

10例HIV/AIDS患者应用抗逆转录病毒药物治疗的探讨

艾滋病病毒(HIV)感染者和艾滋病(AIDS)患者的临床预后很大程度上取决于早期发现,合理筛选,恰当应用抗逆转录病毒治疗(ART)。秭归县疾病预防控制中心自2003年7月~2005年10月,应用中国疾病预防控制中心制定的抗病毒“三联”化疗方案,先后对我县10例HIV/AIDS患者实施了抗病毒治疗,     

2020年阿克苏地区2412例HIV/AIDS病例抗病毒治疗后病毒载量及影响因素分析

目的 了解2020年新疆阿克苏地区HIV/AIDS病例的抗病毒治疗效果,分析影响因素,为提高抗病毒治疗效果提供依据。方法 选取阿克苏地区5个区(县)全部经抗病毒治疗6个月以上的HIV/AIDS病例,采用PCR法检测病毒载量,结合病例流行病学资料分析影响因素。结果 共检测HIV/AIDS病例2 412例,其中625例病毒载量≥1 000 cps/ml,1 787例病毒载量<1 000 cps/ml,抗病毒治疗有效率为74.09%。单因素分析显示,不同年龄(χ^(2)=34.269)和婚姻状况(χ^(2)=124.685)病例的抗病毒治疗有效率差异有统计学意义(P<0.05)。二分类Logistic回归分析显示,年龄31岁及以上是影响抗病毒治疗效果的危险因素(OR=1.941,95%Cl:1.527~2.469),已婚是影响抗病毒治疗效果的保护因素(OR=0.286,95%CI:0.228~0.358)。结论 阿克苏地区HIV/AIDS病例抗病毒治疗有效率有待提高;应以尽早发现、尽早治疗和提高病例依从性为切入点,加强艾滋病宣传工作,进一步提高阿克苏地区HIV/AIDS病例抗病毒治疗有效率。     

212例HIV/AIDS病人抗病毒治疗效果分析

随着国家免费抗病毒治疗在佑安医院展开,越来越多的艾滋病病毒(Human immunodeficiency virus,HIV)感染者/艾滋病(Acquired immune deficiencysyndrome,AIDS)病人(简称HIV/AIDS病人)开始接受抗反转录病毒治疗。到目前为止,已有超过500例HIV/AIDS病人在本院接受抗反转录病毒治疗,其中超过300例治疗周期已经超过24个月。为提高     

中西药结合治疗HIV/AIDS病人8例

<正>艾滋病(Acquired immune deficiency syndrome,AIDS)是由于感染艾滋病病毒(Human immunodeficiency virus,HIV)而引起的以免疫系统损害为特征的综合征,高效抗反转录病毒治疗(Highly active antiretroviral therapy,HAART)是目前全球公认有效的抗病毒治疗方法,能延长HIV/AIDS病     

凉山州HIV/AIDS患者抗病毒治疗启动阶段不依从的质性研究

目的 深入了解四川省凉山州艾滋病病毒(HIV)感染者/艾滋病(AIDS)患者(简称HIV/AIDS患者)抗病毒治疗启动阶段不依从原因,为早日启动抗病毒治疗,提高治疗依从性和有效率提供参考.方法 2019年11月至2020年1月,采用现象学研究方法对凉山州23名HIV/AIDS患者进行半结构化深入访谈,运用Colaizz...     

为抗病毒治疗病人提供关怀服务的实践和体会

抗病毒治疗可以有效降低艾滋病病毒(Human immunodeficiency virus,HIV)感染者和艾滋病(Acquired immunodeficiency syndrome,AIDS)病人(HIV/AIDS病人)的死亡,同时可以降低HIV传播的概率,有效减少传播,已经成为AIDS防治的最有效措施之一。影响患者抗病毒治疗依从性的因素主要包括接受治疗的知识和行为、服药意愿和技能,以     

AIDS抗病毒治疗的历史、现状与未来

高效抗逆转录病毒治疗（highly active antiretroviral therapy,HAART）显著降低了HIV相关疾病的病死率,使HIV／AIDS的临床治疗取得了突破性进展,但HAART不能彻底清除患者体内的病毒。长期服药带来的不良反应、病毒耐药性、患者服药依从性与经济负担等问题已成为抗病毒治疗失败的主要原因。本文就国内外AIDS抗病毒治疗的历史和现状进行回顾,并对抗病毒治疗的未来进行展望。     

Progression of HIV in haemophilia

Summary. The recent elucidation of the life cycle and dynamics of the human immunodeficiency virus (HIV) and technological advances in development of the HIV RNA PCR assay for sensitive detection of viral load have revolutionized the diagnosis, management, and treatment of HIV infection. Beginning with initial infection, there is unremitting, high-level viral replication that persists throughout the course of HIV infection. The measure of the amount of virus present in plasma, HIV viral load, is the single most important predictor of HIV progression, the best indicator of immune system decline, and the best guide for initiating and monitoring antiviral treatment. Further, HIV viral load has become the new yardstick against which other markers, including CD4 number, age, chemokine receptor mutations, cytotoxic T-cell responses, and neutralizing antibody titers are assessed. For individuals with haemophilia, additional ‘markers’ may have significant impact on the outcome of HIV disease. Chronic factor concentrate treatment has led to transfusion-associated hepatitis, co-infection with hepatitis C (HCV), and chronic liver disease. The latter may become accelerated with HIV progression and may lead to hepatotoxicity with antiviral drug therapy. Chronic factor concentrate treatment has also been associated with immunosuppression, including both B- and T-cell immune defects. In HIV(+) haemophilic men, this immune deficit has led to lower CD4 counts with HIV progression and poorer CD4 response to antiviral drugs than in gay men. The underlying haemophilic bleeding tendency may result in significant haemorrhage with HIV-associated immune thrombocytopenia and with protease inhibitor antiretroviral therapy. Although AIDS is the leading cause of death in this group, the reduction in the size of the haemophilia population over the next two centuries is estimated to be small, and survival should improve as better antiviral therapeutics are identified.     

Beyond complacency: the effects of treatment on HIV transmission

The novel optimistic view of the HIV epidemic, which seems to be associated with the success of HIV antiviral therapy and prevention, may lead to an increase in the number of HIV infected people. Overall, risky sexual behaviors are increasing due to optimism regarding the manageability and reduced threat of HIV disease. In addition, the beliefs that some people have regarding the success of treatment and the meaning of viral load are often not supported by scientific research. In order to regain proper prevention methods, misconceptions about the HIV epidemic should be cleared, through greater educational efforts by clinicians, educators, and AIDS service organizations with regards to new treatments, adherence, the meaning of viral activity, and the dangers of drug-resistant viral transmission.     

Tratamiento del herpes zoster en pacientes inmunocompetentes e inmunodeprimidos

Herpes zoster (HZ) is a clinical manifestation of the reactivation of latent varicella zoster virus infection. Patients may have acute neuritic pain, together with cutaneous vesicular lesions in a dermatomal distribution. Recently, new antiviral drugs have been highly useful in the treatment of patients with HZ, avoiding many of the secondary complications that can appear after this herpetic infection. In addition, the rational and early use of these antiviral drugs may reduce the virulence of postherpetic neuralgia in a substantial proportion of patients. Consequently, guidelines for the management and treatment of patients with HZ should be established. Specifically, guidelines should be established for certain patient groups at risk for an atypical or severe clinical course, such as immunosuppressed patients (those with solid organ transplants, HIV infection or AIDS, or patients under immunosuppressive treatment) or pregnant and pediatric patients. In addition, antiviral treatment must be administered with analgesic drugs to control neuritic pain in all patients with HZ, whether in the acute phase or in the form of postherpetic neuralgia.     

Profile of HIV-1 infected patients from an AIDS clinic in Beijing from 2007-2008

While significant progress has been made since 2003 when a comprehensive treatment, prevention and control program was implemented to combat the HIV/AIDS epidemic in China, new challenges are emerging. There have been limited direct case reports on profiles of HIV/AIDS patients under care at unique clinical settings in China despite significant differences between clinics in this part of the world and those in Western countries. In this report, characteristics of HIV/AIDS patients managed during a 12-month period from June 2007 to May 2008 at a major medical school-affiliated AIDS clinic in the center of Beijing are described. Our data confirm an alarming trend of increased rates of sexual transmission of HIV-1 in recent years and suggest that major improvements are needed for both the type of antiviral treatments being used and post-treatment monitoring of viral load. This information will be useful for the continued progress in the clinical management of HIV/AIDS patients in China.     

Tratamiento de la hepatitis C en grupos de pacientes especiales

The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects.These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy.     

Causes of the decline in AIDS deaths, United States, 1995-2002: prevention, treatment or both?

The decline in AIDS deaths in the USA between 1995 and 2002 has been attributed by Centers for Disease Control (CDC) to HIV treatments advances. The purpose of the present study is to assess whether this AIDS deaths decline was due entirely to treatment advances, to earlier prevention successes, or a combination of both. Secondarily, we quantitatively estimate the number of AIDS deaths averted (or delayed) by treatment advances over and above prevention effects. The study employed scenario analysis to address the research questions. To answer the primary research question, we examined whether three key predictions derived from the shape and peak of the HIV incidence curve in the USA (and the natural history of HIV disease in the era before highly active antiretroviral therapy [HAART]) about the shape and peak of the AIDS deaths curve were upheld (e.g., one prediction was that the peak of the AIDS deaths curve should occur 10-12 years after the peak of the HIV incidence curve). To the extent that these predictions are supported, there is evidence that earlier HIV prevention efforts impacted the number of AIDS deaths later in the epidemic. To answer the second research question, the observed annual AIDS deaths curve (1995-2002) was compared with three estimated AIDS deaths curves that may have occurred had HAART never became available. Three estimations were employed to reflect a range of assumptions about the lag between the flattening of HIV incidence in the USA and the flattening of AIDS deaths (i.e., 10, 11 or 12 years). For any one of the three-scenario analyses, the quantitative area between the 'observed' and 'estimated' AIDS deaths curves provide an estimate of the number of AIDS deaths averted by HIV/AIDS treatments. The three predictions from the HIV incidence curve (and the pre-HAART natural history of HIV disease) for determining the shape and peak of the AIDS deaths curve were supported thereby indicating the influence of past prevention efforts on recent AIDS deaths. However, the observed decline in AIDS deaths was more precipitous than predicted (indicating the influence of treatment advances). The scenario analyses indicated that between 33,480 and 41,784 AIDS deaths were averted (or delayed) between 1995 and 2002 as a function of treatment. That is, approximately, 206,037 AIDS deaths occurred between 1995 and 2002 (in the HAART era), but between 239,517 and 247,821 likely would have occurred without the advent of HAART. We conclude that both past prevention and current treatment services have lead to the AIDS deaths decline in the USA, and that HAART has averted between 33,480 and 41,784 AIDS deaths in the USA between 1995 and 2002 over and above the effects of early prevention efforts.     

Liver transplantation for HIV/hepatitis C virus co‐infected patients

Since the introduction of antiretroviral therapy (ART) in the mid‐1990s, AIDS‐related death has been dramatically reduced, and hepatitis‐C‐virus (HCV)‐related liver failure or hepatocellular carcinoma has currently become the leading cause of death in HIV/HCV co‐infected patients. Liver transplantation may be one of the treatments of choices in such cases, but the indications for transplantation, perioperative management including both HIV and HCV treatments, immunosuppression and the prevention/treatment of infectious complications are all still topics of debate. With the improved understanding of the viral behaviors of both HIV and HCV and the development of novel strategies, especially to avoid drug interactions between ART and immunosuppression, liver transplantation has become a realistic treatment for HIV/HCV co‐infected patients.     

HIV/AIDS in Asia

HIV (ie, HIV-1) epidemics in Asia show great diversity, both in severity and timing. But epidemics in Asia are far from over and several countries including China, Indonesia, and Vietnam have growing epidemics. Several factors affect the rate and magnitude of growth of HIV prevalence, but two of the most important are the size of the sex worker population and the frequency with which commercial sex occurs. In view of the present state of knowledge, even countries with low prevalence of infection might still have epidemics affecting a small percentage of the population. Once HIV infection has become established, growing needs for care and treatment are unavoidable and even the so-called prevention-successful countries of Thailand and Cambodia are seeing burgeoning care needs. The manifestations of HIV disease in the region are discussed with the aim of identifying key issues in medical management and care of HIV/AIDS. In particular, issues relevant to developing appropriate highly active antiretroviral treatment programmes in the region are discussed. Although access to antiretroviral therapy is increasing globally, making it work effectively while simultaneously expanding prevention programmes to stem the flow of new infections remains a real challenge in Asia. Genuine political interest and commitment are essential foundations for success, demanding advocacy at all levels to drive policy, mobilise sufficient resources, and take effective action.