HIV therapy最新文献

英文中文

Future treatment for non-AIDS-defining cancers in HIV-infected patients 艾滋病毒感染患者非艾滋病定义癌症的未来治疗

HIV therapy

Pub Date : 2009-07-06 DOI: 10.2217/HIV.09.14

J. Deeken, L. Pantanowitz, B. Dezube

ISSN 1758-4310 10.2217/HIV.09.14 © 2009 Future Medicine Ltd HIV Ther. (2009) 3(4), 311–314 at higher risk for some cancers compared with African–Americans and patients of other ethnic groups [7]. Additional risk factors include behavioral aspects, such as an increased use of tobacco and alcohol in patients with HIV [8]. Research has demonstrated that HIV itself may have direct effects that contribute to the development of NADC. For example, the HIV Tat protein may cause transactivation of protooncogenes [9]. Other genes within the HIV virus may inhibit tumor suppressor genes, including p53. HIV infection may cause microsatellite gene instability and genetic alterations leading towards onco genesis. Tissue infection with HIV may make these t issues more sensitive to the effects of carcinogens from the environment. Finally, HIV infection can cause endothelial abnormalities including pro angiogenesis, which may enhance the development of tumor growth and metastasis [1]. There have been conflicting data regarding whether HAART is associated with the risk of developing NADCs. Some studies have demonstrated a decreased risk of developing a NADC while patients are on HAART, compared with patients who are not receiving antiretroviral therapy or are only on single agent or dual agent antiretroviral therapy [7]. Other studies have demonstrated a possible increased risk if patients are on HAART [4], and specifically if they are on a non-nucleoside reverse transcriptase inhibitorbased therapy [5]. A concerning, recent finding in the large Phase III trial that led to the approval of raltegravir (an integrase inhibitor also known as Isentress [Merck] and MK-0518) was that during the period of the study, patients on raltegravir had a higher risk of developing a NADC compared with those taking placebo [10]. Clearly more research is needed to elucidate the role of antiretroviral therapy, immune reconstitution and the relative risk of developing NADCs. Editorial

ISSN 1758-4310 10.2217/HIV.09.14©2009未来医学有限公司HIV Ther。(2009) 3(4)， 311-314与非裔美国人和其他族裔患者相比，罹患某些癌症的风险更高[7]。其他危险因素包括行为方面，如艾滋病毒患者吸烟和饮酒增加[8]。研究表明，艾滋病毒本身可能直接影响NADC的发展。例如，HIV Tat蛋白可能导致原癌基因的反激活[9]。HIV病毒内的其他基因可能抑制肿瘤抑制基因，包括p53。HIV感染可能导致微卫星基因不稳定和基因改变导致肿瘤发生。组织感染艾滋病毒可能使这些问题对环境致癌物的影响更加敏感。最后，HIV感染可引起内皮异常，包括促血管生成，这可能促进肿瘤生长和转移的发展[1]。关于HAART是否与发生NADCs的风险相关，一直存在相互矛盾的数据。一些研究表明，与未接受抗逆转录病毒治疗或仅接受单药或双药抗逆转录病毒治疗的患者相比，接受HAART治疗的患者发生NADC的风险降低[7]。其他研究表明，如果患者接受HAART治疗，特别是非核苷类逆转录酶抑制剂治疗，风险可能会增加[4]。最近在大型III期试验中，一项令人担忧的发现是，在研究期间，与服用安慰剂的患者相比，服用雷替韦韦(一种整合酶抑制剂，也称为Isentress[默克]和MK-0518)的患者发生NADC的风险更高[10]。显然，需要更多的研究来阐明抗逆转录病毒治疗的作用、免疫重建和发生NADCs的相对风险。编辑

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引用次数: 1

Managing HIV therapy literacy in resource-limited settings 在资源有限的环境中管理艾滋病毒治疗知识

HIV therapy

Pub Date : 2009-07-06 DOI: 10.2217/HIV.09.16

S. Sahay, M. Ghate, S. Mehendale

A program of antiretroviral therapy (ART) roll-out is currently undergoing expansion in India and it is critical to ensure policy makers’ support, sustained commitment to funding and existence of ART literacy even in dispensaries at sub-district levels. There are challenges in ensuring adequate treatment coverage and high levels of adherence. The effectiveness of ART would increase through periodic specialized ART-related training of practitioners of modern and indigenous medicine working in both private and public sectors in India. Treatment literacy among healthcare providers should aim at providing them with basic information regarding ART, how antiretroviral drugs act and why they fail. Investment should be made in the research and development sector towards studying indigenous treatments, drug resistance patterns and unconventional approaches to treatment. Demystification of HIV by clarifying the knowledge gaps and creating awareness through celebrities, iconic individuals and opinion leaders may sig...

印度目前正在扩大一项抗逆转录病毒疗法(ART)推广计划，关键是要确保决策者的支持、对资金的持续承诺以及即使在街道一级的药房也存在抗逆转录病毒疗法知识。在确保充分的治疗覆盖率和高水平的依从性方面存在挑战。通过定期对在印度私营和公共部门工作的现代和土著医学从业人员进行与抗逆转录病毒治疗有关的专门培训，抗逆转录病毒治疗的有效性将得到提高。卫生保健提供者的治疗素养应旨在向他们提供有关抗逆转录病毒疗法、抗逆转录病毒药物如何起作用以及它们为何失效的基本信息。应该在研究和发展部门进行投资，以研究当地的治疗方法、耐药性模式和非传统的治疗方法。通过澄清知识差距和通过名人，标志性的个人和意见领袖创造意识，消除艾滋病毒的神秘性。

引用次数: 8

Tesamorelin: a synthetic growth hormone-releasing factor analog for the treatment of HIV-associated lipodystrophy 替沙莫林:一种用于治疗hiv相关脂肪营养不良的合成生长激素释放因子类似物

HIV therapy

Pub Date : 2009-07-06 DOI: 10.2217/HIV.09.24

Ying Wang, B. Tomlinson

HIV-associated lipodystrophy has become a major challenge in the treatment of HIV infection. Recombinant human growth hormone has shown clinical effectiveness in therapy for growth hormone-deficient disorders and HIV-associated lipodystrophy, but its association with a variety of adverse effects has led to the development of human growth hormone-releasing factor analogs. Tesamorelin, a synthetic growth hormone-releasing factor, has been developed for the potential treatment of HIV-associated lipodystrophy. A multicenter, randomized, placebo-controlled, Phase III clinical trial demonstrated that tesamorelin was a beneficial treatment strategy for HIV-associated lipodystrophy with a good safety profile and a positive effect on reducing visceral fat and improving lipid profiles.

HIV相关的脂肪营养不良已经成为HIV感染治疗的主要挑战。重组人生长激素在治疗生长激素缺乏症和hiv相关脂肪营养不良方面已显示出临床有效性，但其与各种不良反应的关联导致了人生长激素释放因子类似物的发展。替沙莫瑞林是一种合成生长激素释放因子，已被开发用于hiv相关脂肪营养不良的潜在治疗。一项多中心、随机、安慰剂对照的III期临床试验表明，替沙莫林是hiv相关脂肪营养不良的一种有益治疗策略，具有良好的安全性和减少内脏脂肪和改善脂质谱的积极作用。

引用次数: 0

Monitoring HIV drug resistance in treatment-naive individuals: molecular indicators, epidemiology and clinical implications. 监测HIV耐药性在治疗初期个体:分子指标，流行病学和临床意义。

HIV therapy

Pub Date : 2009-07-06 DOI: 10.2217/HIV.09.23

E. Magiorkinis, M. Detsika, A. Hatzakis, D. Paraskevis

Transmitted drug resistance (TDR) has been documented to occur soon after the introduction of HAART. The purpose of this review is to summarize the current knowledge regarding the epidemiology, the clinical implications and the trends in the research field of TDR. Until now, there have been different approaches for monitoring TDR, however, the surveillance drug resistance-associated mutations list seems fairly advantageous for TDR surveillance compared with other methods. The prevalence of TDR is approximately 10% in Europe and North America among recently or newly infected individuals sampled over the last few years. TDR was found to be higher among patients infected in Europe and North America compared with those in geographic areas with a high prevalence of HIV-1, reflecting the differences in the access to HAART in the two populations. Resistant viruses show different reversal rates to wild-type depending on the fitness cost of particular mutations. TDR in treatment-naive individuals is of major impor...

据记载，在采用HAART治疗后不久就发生了传播性耐药。本文综述了TDR的流行病学、临床意义和研究趋势。到目前为止，已有不同的TDR监测方法，然而，与其他方法相比，监测耐药相关突变列表似乎对TDR监测相当有利。在欧洲和北美，在过去几年取样的最近或新感染的个体中，热带病流行率约为10%。研究发现，与艾滋病毒-1高流行地区的患者相比，欧洲和北美感染患者的热带病发病率更高，这反映了这两个人群在获得HAART治疗方面的差异。抗性病毒对野生型表现出不同的逆转率，这取决于特定突变的适应度成本。TDR在未接受治疗的个体中非常重要。

引用次数: 5

Future directions in the treatment of HIV-HBV coinfection. HIV-HBV合并感染治疗的未来方向。

HIV therapy

Pub Date : 2009-07-01 DOI: 10.2217/hiv.09.19

David M Iser, Sharon R Lewin

Liver disease is a major cause of mortality in individuals with HIV-HBV coinfection. The pathogenesis of liver disease in this setting is unknown, but is likely to involve drug toxicity, infection of hepatic cells with both HIV and HBV, and an altered immune response to HBV. The availability of therapeutic agents that target both HIV and HBV replication enable dual viral suppression, and assessment of chronic hepatitis B is important prior to commencement of antiretroviral therapy. Greater importance is now placed on HBV DNA levels and staging of liver fibrosis, either by liver biopsy or noninvasive measurement, such as transient elastography, since significant liver fibrosis may exist in the presence of normal liver function tests. Earlier treatment of both HIV and HBV is now generally advocated and treatment is usually lifelong.

肝脏疾病是HIV-HBV合并感染患者死亡的主要原因。在这种情况下，肝脏疾病的发病机制尚不清楚，但可能涉及药物毒性、肝细胞感染HIV和HBV以及对HBV的免疫反应改变。靶向HIV和HBV复制的治疗药物的可用性使双重病毒抑制成为可能，并且在开始抗逆转录病毒治疗之前对慢性乙型肝炎进行评估是重要的。HBV DNA水平和肝纤维化分期(通过肝活检或非侵入性测量，如瞬时弹性成像)现在受到更大的重视，因为在肝功能检查正常的情况下可能存在明显的肝纤维化。现在普遍提倡HIV和HBV的早期治疗，治疗通常是终身的。

引用次数: 8

Clinical implications of new findings in HIV basic research. HIV基础研究新发现的临床意义。

HIV therapy

Pub Date : 2009-07-01 DOI: 10.2217/hiv.09.20

Manish Sagar

HIV has been studied extensively over the past 25 years. Insights into the different stages of the virus' replication cycle and its interaction with host-cell proteins have led to the development of an armamentarium of effective antiretroviral medications. These antiviral drugs have dramatically changed the prognosis for HIV-infected subjects from an inevitable march towards death to a chronic disease with a potentially normal lifespan. Even with these successes, there is a continuing need to provide new drugs, especially those effective against drug-resistant viruses, to devise optimal strategies to prevent adverse events from either immunosuppression or the antiretroviral medications, and to develop treatments aimed at eliminating virus replication in the absence of antiviral drugs. In this review, how these important issues are being addressed will be highlighted, emphasizing clinical implications from some recent basic science studies and demonstrating how they could change the face of HIV therapeutics over the next 5-10 years.

在过去的25年里，人们对艾滋病毒进行了广泛的研究。对病毒复制周期的不同阶段及其与宿主细胞蛋白的相互作用的深入了解，导致了一系列有效抗逆转录病毒药物的开发。这些抗病毒药物极大地改变了hiv感染者的预后，从不可避免地走向死亡变成了一种可能正常寿命的慢性疾病。即使取得了这些成功，仍然需要继续提供新的药物，特别是对耐药病毒有效的药物，制定最佳战略以防止免疫抑制或抗逆转录病毒药物造成的不良事件，并开发旨在在没有抗病毒药物的情况下消除病毒复制的治疗方法。在这篇综述中，将强调如何解决这些重要问题，强调最近一些基础科学研究的临床意义，并展示它们如何在未来5-10年内改变艾滋病毒治疗的面貌。

引用次数: 2

Type I interferon in HIV treatment: from antiviral drug to therapeutic target. I 型干扰素在 HIV 治疗中的应用：从抗病毒药物到治疗目标。

HIV therapy

Pub Date : 2009-05-01 Epub Date: 2009-04-30 DOI: 10.2217/hiv.09.8

Adriano Boasso

Type I interferons (IFNs) are soluble molecules that exert potent antiviral activity and are currently used for the treatment of a panel of viral infections. In the case of HIV, the use of type I IFN has had limited success, and has almost been abandoned. During the last decade, a series of studies has highlighted how HIV infection may cause overactivation of type I IFN production, which contributes to the exhaustion of the immune system and to disease progression. This review describes the transition from the proposed use of type I IFN as antiviral drugs in HIV infection, to the idea that blocking their activity or production may provide an immunologic benefit of much greater importance than their antiviral activity.

I 型干扰素（IFN）是一种可溶性分子，具有强大的抗病毒活性，目前被用于治疗多种病毒感染。对于艾滋病病毒，I 型干扰素的使用效果有限，几乎已被放弃。过去十年间，一系列研究强调了艾滋病病毒感染如何可能导致 I 型 IFN 的过度激活，从而导致免疫系统衰竭和疾病进展。本综述描述了 I 型因子作为抗病毒药物用于艾滋病病毒感染的建议，到阻断 I 型因子的活性或产生可能带来比其抗病毒活性更重要的免疫学益处这一观点的转变。

引用次数: 0

HIV/AIDS in private sector companies: cost impacts and responses in southern Africa 私营部门公司的艾滋病毒/艾滋病:南部非洲的成本影响和对策

HIV therapy

Pub Date : 2009-04-30 DOI: 10.2217/HIV.09.10

G. George, J. Gow, A. Whiteside

The effects of the HIV epidemic, particularly in southern Africa, have been increasingly experienced by companies in recent years. Initially, the lag in presentation of morbidity and mortality allowed companies to ignore the epidemic. However, in the past decade, companies have been confronted with the cost impacts of seriously ill and dying employees. Companies in many countries in the region are strongly engaged in generating effective prevention, and treatment and care responses to the epidemic. However, many small and medium size companies ignore the problem, due to inadequate resources. Nonetheless, some large companies are pioneering best practices in workplace HIV/AIDS programs in prevention, and care and treatment.

近年来，各公司日益感受到艾滋病毒流行病的影响，特别是在南部非洲。最初，由于发病率和死亡率的统计滞后，公司可以忽略这种流行病。然而，在过去的十年里，公司面临着重病和死亡员工的成本影响。该区域许多国家的公司积极参与制定针对该流行病的有效预防、治疗和护理对策。然而，由于资源不足，许多中小企业忽视了这个问题。尽管如此，一些大公司在工作场所的艾滋病预防、护理和治疗项目中率先采取了最佳做法。

引用次数: 19

Pediatric adherence to antiretroviral therapy in resource-poor settings: challenges and future perspectives 资源贫乏环境下儿童抗逆转录病毒治疗依从性:挑战和未来展望

HIV therapy

Pub Date : 2009-04-30 DOI: 10.2217/HIV.09.2

F. Pérez, V. Leroy

The HIV pediatric epidemic in low-income countries is still growing with an increasing impact on children. By the end of 2007, more than 2 million children under 15 years of age worldwide were living with HIV, 90% in subSaharan Africa. In that year alone, 370,000 children were newly infected and 270,000 died. AIDS has become one of the leading causes of mortality among children under the age of 5 years in developing countries [101]. In the absence of combination antiretroviral therapy (cART), 52% of children infected with perinatally acquired HIV infection will die by the age of 2 years [1]. Numerous studies have confirmed the clinical efficacy and feasibility of cART in HIVinfected adults in Africa [2,3] but, to date, resources and programs targeting HIV-infected children in resource-poor settings remain limited. Even though the use of cART to treat children has increased in recent years in subSaharan Africa, less than 15% of children needing cART in Africa currently receive it [102]. It is estimated that more than 780,000 children are in need of cART in lowand middle-income countries [103]. When made accessible, treatment for children in this context has proved highly effective [4]. Studies have found the survival probability at 12 months for children on cART to be more than 95% in settings in sub-Saharan Africa [5] and Asia [6]. Education and adherence counseling are therefore essential components of cART and adherence in HIV-infected children is critical to the success of cART.

艾滋病毒儿科流行病在低收入国家仍在增长，对儿童的影响越来越大。到2007年底，全世界有200多万15岁以下儿童感染艾滋病毒，其中90%在撒哈拉以南非洲。仅在那一年，就有37万儿童新感染，27万儿童死亡。艾滋病已成为发展中国家5岁以下儿童死亡的主要原因之一[101]。在没有抗逆转录病毒联合治疗(cART)的情况下，52%感染围产期获得性艾滋病毒的儿童将在2岁前死亡[1]。许多研究证实了cART在非洲hiv感染成人中的临床疗效和可行性[2,3]，但迄今为止，针对资源贫乏地区hiv感染儿童的资源和规划仍然有限。尽管近年来在撒哈拉以南非洲使用cART治疗儿童的情况有所增加，但目前非洲需要cART治疗的儿童中只有不到15%得到了治疗[102]。据估计，中低收入国家有超过78万名儿童需要cART[103]。在这种情况下，对儿童的治疗被证明是非常有效的[4]。研究发现，在撒哈拉以南非洲[5]和亚洲[6]的环境中，接受cART治疗的儿童12个月生存率超过95%。因此，教育和依从性咨询是cART的重要组成部分，艾滋病毒感染儿童的依从性对cART的成功至关重要。

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引用次数: 1

Promising novel compounds for the generation of new anti-HIV-RT therapeutic drugs 有希望的新化合物产生新的抗hiv - rt治疗药物

HIV therapy

Pub Date : 2009-04-30 DOI: 10.2217/HIV.09.3

T. M. Souza, Carlos Frederico Leite Fontes

The recent literature has highlighted several classes of antiretrovirals used as powerful weapons against AIDS. Current antiretrovirals include drugs that act as inhibitors of integrase, protease or even the fusion entry step of HIV-1. However, reverse transcriptase remains an attractive target for new anti-HIV-1 drug design. The clinical base already established and relatively low cytotoxicity support reverse transcriptase inhibitors as an important field of research and also a fruitful source of potentially new antiretrovirals. The goal of this article is to provide an overview of some recently approved drugs and drug candidates, which are endowed with novel mechanisms of action, and to discuss new approaches that may be an alternative to clinically available reverse transcriptase inhibitors. Some of these drugs are promising options for future treatments against multiresistant HIV-1 strains found in treatment-experienced patients.

最近的文献强调了几类抗逆转录病毒药物被用作对抗艾滋病的有力武器。目前的抗逆转录病毒药物包括作为整合酶、蛋白酶甚至HIV-1融合进入步骤抑制剂的药物。然而，逆转录酶仍然是新的抗hiv -1药物设计的一个有吸引力的目标。已经建立的临床基础和相对较低的细胞毒性支持逆转录酶抑制剂作为一个重要的研究领域，也是潜在的新型抗逆转录病毒药物的富有成效的来源。本文的目的是概述一些最近批准的药物和候选药物，这些药物被赋予了新的作用机制，并讨论可能替代临床可用的逆转录酶抑制剂的新方法。其中一些药物是未来治疗在治疗经验丰富的患者中发现的多重耐药HIV-1毒株的有希望的选择。

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