HIV therapy最新文献

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Treatment and prevention of cytomegalovirus-associated diseases in HIV - 1 infection in the era of HAART HAART时代HIV - 1感染巨细胞病毒相关疾病的治疗和预防

HIV therapy

Pub Date : 2010-07-07 DOI: 10.2217/HIV.10.30

D. Meyer-Olson, R. Schmidt, Benjamin A. Bollmann

Cytomegalovirus (CMV) infection is one of the most common chronic viral infections and is one of the most important opportunistic infections in HIV-infected patients. Although HAART has substantially improved the morbidity and mortality of HIV-infected patients and decreased the frequencies of AIDS-related diseases, opportunistic infections including CMV end-organ diseases still remain a significant clinical challenge. Here we review the clinical manifestation and diagnosis of CMV end-organ diseases including the potential role of CMV infection in the pathogenesis of cardiovascular disease. We explain how HAART has changed the epidemiology of CMV disease in HIV infection and discuss how this influences current treatment guidelines for the prevention of CMV disease and CMV-associated immune recovery syndrome.

巨细胞病毒(CMV)感染是最常见的慢性病毒感染之一，也是hiv感染者中最重要的机会性感染之一。尽管HAART大大改善了艾滋病毒感染者的发病率和死亡率，并降低了艾滋病相关疾病的发病率，但包括巨细胞病毒终末器官疾病在内的机会性感染仍然是一个重大的临床挑战。本文综述巨细胞病毒终末器官疾病的临床表现和诊断，包括巨细胞病毒感染在心血管疾病发病机制中的潜在作用。我们解释HAART如何改变HIV感染中巨细胞病毒疾病的流行病学，并讨论这如何影响当前预防巨细胞病毒疾病和巨细胞病毒相关免疫恢复综合征的治疗指南。

引用次数: 8

HIV diagnostics: challenges and opportunities 艾滋病毒诊断:挑战与机遇

HIV therapy

Pub Date : 2010-07-07 DOI: 10.2217/HIV.10.29

E. Wong, I. Hewlett

Accurate HIV diagnostic testing continues to pose challenges, but there are also opportunities for assay performance improvements in key areas for specific intended-use settings. The genetic diversity of HIV can result in false and discordant results in assays that fail to detect new variant strains. The use of antiretroviral therapies has resulted in drug-resistant variants that require monitoring by sequencing and genotyping methods. Nucleic acid testing is the most sensitive and reliable platform for detection, but it is costly and limited to centralized testing facilities, making implementation difficult in resource-limited settings where HIV has hit the hardest. Rapid antibody tests suitable for point-of-care use are becoming more accessible in resource-limited settings, but these tests may not detect HIV during the acute infection stage. Emerging antigen/antibody combination assays are viable alternatives to nucleic acid testing for diagnosis of recent infections. Although patient monitoring (e.g., ...

准确的艾滋病毒诊断检测继续构成挑战，但在特定预期使用环境的关键领域也存在改进检测性能的机会。艾滋病毒的遗传多样性可能导致无法检测到新的变异株的检测结果错误和不一致。抗逆转录病毒疗法的使用导致了耐药变异，需要通过测序和基因分型方法进行监测。核酸检测是最敏感、最可靠的检测平台，但它成本高昂，而且仅限于集中检测设施，这使得在艾滋病毒最严重的资源有限的环境中难以实施。在资源有限的环境中，适合在护理点使用的快速抗体检测越来越容易获得，但这些检测可能无法在急性感染阶段检测到艾滋病毒。新出现的抗原/抗体联合检测是核酸检测诊断近期感染的可行替代方法。尽管病人监护(例如，……

引用次数: 11

Micronutrients and HIV infection 微量营养素和艾滋病毒感染

HIV therapy

Pub Date : 2010-07-07 DOI: 10.2217/HIV.10.36

A. Campa, M. Baum

The immune system requires several essential micronutrients to maintain an effective immune response. HIV infection destroys the immune system and promotes nutritional deficiencies, which further impair immunity. This article reviews the role of several micronutrients (vitamins A, C, E and D, the B vitamins, and minerals, selenium, iron and zinc) that are relevant for maintaining immune function. In addition, the deficiencies of these micronutrients have been associated with faster progression of HIV-1 disease. This review examines the evidence from observational studies of an association between micronutrient status and HIV disease, as well as the effectiveness of micronutrient supplementation on HIV-disease progression, pregnancy outcomes and nutritional status, among others, utilizing randomized clinical trials. Each micronutrient is introduced with a summary of its functions in human physiology, followed by the presentation of studies conducted in HIV-infected patients in relation to this specific mic...

免疫系统需要几种必需的微量营养素来维持有效的免疫反应。HIV感染会破坏免疫系统，导致营养缺乏，从而进一步损害免疫力。本文综述了几种微量营养素(维生素A, C, E和D, B族维生素，矿物质，硒，铁和锌)在维持免疫功能方面的作用。此外，这些微量营养素的缺乏与HIV-1疾病的更快进展有关。本综述利用随机临床试验，研究了微量营养素状况与艾滋病毒疾病之间关联的观察性研究证据，以及微量营养素补充对艾滋病毒疾病进展、妊娠结局和营养状况等的有效性。介绍了每种微量营养素，并简要介绍了其在人体生理学中的功能，然后介绍了在艾滋病毒感染患者中进行的与这种特定微量营养素相关的研究。

引用次数: 4

Effect of maternal HIV infection on measles susceptibility during early infancy: implications for optimizing protection of the infant. 母婴HIV感染对婴儿早期麻疹易感性的影响:优化婴儿保护的意义。

HIV therapy

Pub Date : 2010-07-07 DOI: 10.2217/HIV.10.31

A. Kruczek, C. Cutland, S. Madhi

The measles virus was first isolated as the causative pathogen of measles approximately 50 years ago by John Enders and Thomas Peebles. Despite a safe and effective vaccine extant for nearly the same amount of time, control of measles nevertheless remains a challenge in developing countries. This article investigates the possible contribution of maternal HIV infection on measles susceptibility in infants. The current WHO position on measles vaccination in HIV-infected children recommends vaccinating asymptomatic HIV-infected infants as early as 6 months of age, followed with two additional doses at 9 and 18 months. This is rarely implemented due to logistical constraints related to early HIV diagnosis in infants and access to vaccines in low-resource settings. In addition, measles vaccine safety and immunogenicity in HIV-infected children are based on very low levels of scientific evidence. There are no specific recommendations for measles immunization of HIV-uninfected children born to HIV-infected mothe...

大约50年前，约翰·恩德斯和托马斯·皮布尔斯首次将麻疹病毒作为麻疹的致病病原体分离出来。尽管一种安全有效的疫苗已经存在了几乎相同的时间，但在发展中国家，控制麻疹仍然是一项挑战。本文探讨母婴HIV感染对婴儿麻疹易感性的可能贡献。世卫组织目前对感染艾滋病毒的儿童进行麻疹疫苗接种的立场建议，早在6个月大的无症状感染艾滋病毒的婴儿接种疫苗，然后在9个月和18个月时再接种两次。由于与婴儿早期艾滋病毒诊断和在资源匮乏的环境中获得疫苗有关的后勤限制，这种做法很少得到实施。此外，麻疹疫苗在感染艾滋病毒儿童中的安全性和免疫原性所依据的科学证据水平非常低。对感染艾滋病毒的母亲所生的未感染艾滋病毒的儿童进行麻疹免疫接种尚无具体建议。

引用次数: 6

HIV gene therapy that's not a SIN HIV基因疗法不是罪恶

HIV therapy

Pub Date : 2010-07-07 DOI: 10.2217/HIV.10.32

Min-Hsuan Lin, H. Sivakumaran, D. Harrich

Evaluation of: Wang Z, Tang Z, Zheng Y et al.: Development of a nonintegrating Rev-dependent lentiviral vector carrying diphtheria toxin A chain and human TRAF6 to target HIV reservoirs. Gene Ther. (2010) (Epub ahead of print). HIV infection is incurable, but can be effectively controlled by antiviral therapy using a combination of drugs. HIV persistence during therapy is attributed to long-lived cells harboring genome-integrated HIV maintained in a transcriptionally silent state, which are refractory to current antiviral drugs. Transient and periodic activation of HIV in these cellular reservoirs leads to continual viremia. Wang et al. tackle the question of whether gene therapy using nonintegrating lentiviral vectors expressing cytotoxic proteins can specifically target HIV-infected cells. This approach has advantages since there is little chance of tumorigenesis through activation or mutation of proto-oncogenes typically associated with integrating viral vectors. These conditional vectors also express ...

王志，唐志，郑勇等。携带白喉毒素a链和人TRAF6靶向HIV病毒库的非整合rev依赖慢病毒载体的建立。其他的基因。(2010) (Epub，未付印)。艾滋病毒感染是无法治愈的，但可以通过使用药物组合的抗病毒治疗有效地控制。HIV在治疗期间的持续存在归因于携带基因组整合HIV的长寿命细胞维持在转录沉默状态，这对当前的抗病毒药物是难治的。HIV在这些细胞储存库中的短暂和周期性激活导致持续的病毒血症。Wang等人解决了使用表达细胞毒性蛋白的非整合慢病毒载体进行基因治疗是否能够特异性靶向hiv感染细胞的问题。这种方法具有优势，因为通过激活或突变通常与整合病毒载体相关的原癌基因来发生肿瘤的可能性很小。这些条件向量也表示…

引用次数: 1

Innate immune natural killer cells and their role in HIV and SIV infection. 先天免疫自然杀伤细胞及其在 HIV 和 SIV 感染中的作用。

HIV therapy

Pub Date : 2010-07-01 DOI: 10.2217/HIV.10.28

Pavel Bostik, Yoshiaki Takahashi, Ann E Mayne, Aftab A Ansari

The findings that early events during HIV-1 and SIV infection of Asian rhesus macaques dictate the levels of viremia and rate of disease progression prior to the establishment of mature and effective adaptive immune responses strongly suggest an important role for innate immune mechanisms. In addition, the fact that the major target of HIV and SIV during this period of acute infection is the gastrointestinal tissue suggests that whatever role the innate immune system plays must either directly and/or indirectly focus on the GI tract. The object of this article is to provide a general overview of the innate immune system with a focus on natural killer (NK) cells and their role in the pathogenesis of lentivirus infection. The studies summarized include our current understanding of the phenotypic heterogeneity, the putative functions ascribed to the subsets, the maturation/differentiation of NK cells, the mechanisms by which their function is mediated and regulated, the studies of these NK-cell subsets, with a focus on killer cell immunoglobulin-like receptors (KIRs) in nonhuman primates and humans, and finally, how HIV and SIV infection affects these NK cells in vivo. Clearly much has yet to be learnt on how the innate immune system influences the interaction between lentiviruses and the host within the GI tract, knowledge of which is reasoned to be critical for the formulation of effective vaccines against HIV-1.

在亚洲猕猴感染 HIV-1 和 SIV 的早期，在建立成熟有效的适应性免疫反应之前，病毒血症的水平和疾病进展的速度就已决定，这一发现有力地表明了先天性免疫机制的重要作用。此外，HIV 和 SIV 在急性感染期间的主要目标是胃肠道组织，这一事实表明，无论先天性免疫系统发挥何种作用，都必须直接和/或间接地集中于胃肠道。本文旨在概述先天性免疫系统，重点是自然杀伤（NK）细胞及其在慢病毒感染发病机制中的作用。所总结的研究包括我们目前对表型异质性的理解、赋予亚群的假定功能、NK 细胞的成熟/分化、介导和调节其功能的机制、对这些 NK 细胞亚群的研究（重点是非人灵长类动物和人类的杀伤细胞免疫球蛋白样受体 (KIR)），以及最后，HIV 和 SIV 感染如何在体内影响这些 NK 细胞。关于先天性免疫系统如何影响慢病毒和宿主在消化道内的相互作用，显然还有很多知识有待学习，而这方面的知识对于制定有效的 HIV-1 疫苗至关重要。

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引用次数: 0

Neurocognitive disorders during antiretroviral treatment, despite full HIV RNA suppression 抗逆转录病毒治疗期间的神经认知障碍，尽管完全抑制HIV RNA

HIV therapy

Pub Date : 2010-05-04 DOI: 10.2217/HIV.10.24

J. Arribas, A. Hill

After the introduction of HAART in the late 1990s, there were dramatic reductions in HIVrelated neurological disorders such as dementia, CNS lymphoma and cerebral toxoplasmosis [1]. However, minor neurocognitive disorders are still detected in a high proportion of patients receiving antiretrovirals, even if HIV RNA levels are suppressed below 50 copies/ml in plasma [2,3]. HIV-associated neurocognitive disorders are defined by asymptomatic neurocognitive impairment, minor neurocognitive disorders and HIV-associated dementia. These disorders are identified either by clinical diagnosis and/or neurocognitive testing. In some studies, samples of cerebrospinal fluid (CSF) have been tested for HIV RNA and plasma PK levels of antiretrovirals. There is a background incidence of neurological disorders in the general population [4,5], and there may be other confounding factors such as recreational drug use, psychiatric illness, a lcohol abuse/use and hepatitis B or C infection [6].

在20世纪90年代末引入HAART后，艾滋病毒相关的神经系统疾病，如痴呆、中枢神经系统淋巴瘤和脑弓形虫病等显著减少[1]。然而，在接受抗逆转录病毒治疗的患者中，即使血浆中HIV RNA水平被抑制在50拷贝/毫升以下，仍有很大比例的患者检测到轻微的神经认知障碍[2,3]。hiv相关神经认知障碍被定义为无症状神经认知障碍、轻微神经认知障碍和hiv相关痴呆。这些疾病可以通过临床诊断和/或神经认知测试来确定。在一些研究中，对脑脊液(CSF)样本进行了HIV RNA和血浆中抗逆转录病毒药物PK水平的检测。一般人群中存在神经系统疾病的背景发病率[4,5]，可能存在其他混杂因素，如娱乐性药物使用、精神疾病、酒精滥用/使用和乙型或丙型肝炎感染[6]。

引用次数: 3

Management of oropharyngeal and esophageal candidiasis in patients with HIV infection. HIV感染患者口咽和食管念珠菌病的治疗。

HIV therapy

Pub Date : 2010-05-04 DOI: 10.2217/HIV.10.18

J. Vázquez

Mucocutaneous candidiasis is frequently one of the first signs of HIV infection. Over 90% of patients with AIDS will develop oropharyngeal candidiasis at some time during their illness. Although numerous antifungal agents have been developed, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole, voriconazole and posaconazole), have replaced older topical antifungals (gentian violet and nystatin) in the management of oropharyngeal candidiasis in these patients. The systemic azoles are generally safe and effective agents in HIV-infected patients with oropharyngeal candidiasis. A constant concern in these patients are relapses, which depend on the degree of immunosuppression and are commonly encountered after topical therapy rather than with systemic azole therapy. In patients with fluconazole-refractory mucosal candidiasis, treatment options now include itraconazole solution, voriconazole, posaconazole and the newer echinocandins (caspofungin, micafungin and anidulafungin). The object...

皮肤粘膜念珠菌病通常是HIV感染的最初症状之一。超过90%的艾滋病患者在发病期间会出现口咽念珠菌病。虽然已经开发出了许多抗真菌药物，但在治疗这些患者的口咽念珠菌病方面，无论是外用(克曲康唑)还是全身(氟康唑、伊曲康唑、伏立康唑和泊沙康唑)的唑类药物已经取代了较老的外用抗真菌药物(龙胆紫和制霉菌素)。全身唑类药物对hiv感染口咽念珠菌病患者通常是安全有效的药物。这些患者一直关注的是复发，这取决于免疫抑制的程度，通常在局部治疗后而不是全身治疗后遇到。对于氟康唑难治性粘膜念珠菌病患者，目前的治疗方案包括伊曲康唑溶液、伏立康唑、泊沙康唑和较新的棘白菌素(卡泊芬津、米卡芬津和阿尼杜拉芬津)。对象……

引用次数: 5

Tenofovir disoproxil fumarate and the kidney in HIV-infected patients: the evidence thus far. 富马酸替诺福韦二氧吡酯和hiv感染患者的肾脏:迄今为止的证据。

HIV therapy

Pub Date : 2010-05-04 DOI: 10.2217/HIV.10.16

M. Danjuma, A. Mohiuddin, M. Pirmohamed, S. Khoo

Tenofovir disoproxil fumarate (TDF) is an integral part of the initial treatment regimen for HIV and a subgroup of hepatitis B coinfected patients, after its safety and efficacy were demonstrated in a number of prospective studies. However, concerns still remain regarding its potential for kidney injury. The nature of kidney involvement is variable, with various phenotypes reported in different studies. Proximal kidney tubular dysfunction (PKTD) has been reported as one of the commonly recurring phenotypes from most studies. The exact mechanism of TDF-induced PKTD is unknown, but it has been suggested to be due to a combination of functional polymorphisms in the genes that encode efflux transporter proteins and raised proximal tubular cell concentrations of TDF, resulting in oxidative stress and mitochondrial dysfunction. Gaps still remain in our understanding of this novel concept of TDF-induced kidney toxicity, and conflicting observations are made with accumulating evidence. For instance, whether HIV p...

富马酸替诺福韦二氧吡酯(TDF)在一系列前瞻性研究中证明其安全性和有效性后，已成为艾滋病毒和乙型肝炎合并感染患者初始治疗方案中不可或缺的一部分。然而，对其潜在的肾损伤的担忧仍然存在。肾脏受累的性质是可变的，在不同的研究中报告了不同的表型。近端肾小管功能障碍(PKTD)已被报道为大多数研究中常见的复发表型之一。TDF诱导PKTD的确切机制尚不清楚，但有人认为这是由于编码外排转运蛋白的基因的功能多态性和近端小管细胞TDF浓度升高的组合，导致氧化应激和线粒体功能障碍。我们对tdf诱导的肾毒性这一新概念的理解仍然存在差距，并且随着证据的积累，观察结果也相互矛盾。例如，HIV是否……

引用次数: 1

The DUET trials: etravirine in the management of treatment-experienced HIV-1-infected patients DUET试验:依曲维林在治疗经验的hiv -1感染患者的管理

HIV therapy

Pub Date : 2010-05-04 DOI: 10.2217/HIV.10.14

A. Mills

The non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine has been approved for use in treatment-experienced, HIV-1-infected patients. The Phase III DUET trials evaluated the long-term efficacy and safety of etravirine versus placebo, each in combination with an antiretroviral background regimen including twice-daily darunavir/ritonavir 600/100 mg, in treatment-experienced patients failing therapy (with baseline plasma viral load of more than 5000 copies/ml and NNRTI and protease inhibitor resistance). At week 24 in DUET-1, 56% of etravirine-treated patients reached the primary end point of viral load below 50 copies/ml compared with 39% of placebo-treated patients (p = 0.0050); in DUET-2, response rates were 62 versus 44%, respectively (p = 0.0003). Pooled data at weeks 48 and 96 confirmed the durability of response with etravirine. With the exception of rash, the safety and tolerability profile of etravirine was similar to that of placebo over the treatment period. Etravirine is expected to ...

非核苷类逆转录酶抑制剂(NNRTI) etravirine已被批准用于治疗经验丰富的hiv -1感染患者。三期DUET试验评估了依曲维林与安慰剂的长期疗效和安全性，在治疗失败的患者(基线血浆病毒载量超过5000拷贝/ml, NNRTI和蛋白酶抑制剂耐药)中，每项试验均与抗逆转录病毒背景方案联合使用，包括每日两次达鲁那韦/利托那韦600/100 mg)。在DUET-1治疗的第24周，56%的依曲维林治疗的患者达到了病毒载量低于50拷贝/ml的主要终点，而安慰剂治疗的患者为39% (p = 0.0050);在DUET-2中，有效率分别为62%和44% (p = 0.0003)。48周和96周的汇总数据证实了依曲维林反应的持久性。除皮疹外，在治疗期间，依曲维林的安全性和耐受性与安慰剂相似。Etravirine预计会…

引用次数: 1

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