highly active antiretroviral therapy

高效抗逆转录病毒疗法
  • 文章类型: Journal Article
    监测慢性病,尤其是肾脏疾病,在艾滋病毒感染者(PLWH)中至关重要。这里,在电子搜索引擎和PubMed等数据库中进行了系统的搜索,Scopus,和谷歌学者,从开始之日起至2023年12月,以确定报告PLWH炎症与肾功能之间任何关联的相关研究。同行评审期刊中只有六项临床研究符合纳入标准,涉及1467名年龄在37至51岁之间的参与者,其中约17%为女性。该报告强调了高效抗逆转录病毒疗法(HAART)对PLWH肾功能的潜在影响,强调监测炎症标志物作为肾功能指标的重要性,即使HAART有效。承认研究的局限性,特别是相关研究的匮乏,研究结果强调需要更多的研究来指导临床,以优化艾滋病毒管理,特别是关于肾脏健康和HAART方案。尽管评估的研究非常有限,本研究为今后研究揭示HAART之间的复杂关系奠定了重要基础,炎症标志物,和PLWH的肾脏健康。
    Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.
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  • 文章类型: Journal Article
    一种新药可以起源于任何一种制药公司,生物技术或学术界。总的来说,在制药和生物技术领域工作的科学家比他们的学术同行有优势,相关的优势和劣势进行了深入讨论。尽管困难重重,越来越多的重要药物起源于学术界。本文报道了利奥塔研究小组(LRG)的三个案例研究,其中探讨了使这些药物开发运动取得成功的特殊情况。第一个涉及抗逆转录病毒药物,恩曲他滨.在这种情况下,有效的合成方法,在LRG中开发的,再加上一些重点大学和商业部门的伙伴关系,使一群学术合作者发现并开发了一种高效的HIV逆转录酶抑制剂。第二个案例研究涉及突破性的丙型肝炎药物的发现和开发,sofosbuvir.根据埃默里大学Schinazi和Liotta教授的关键输入,埃默里初创公司的科学家,Pharmasset,确定了将成为索非布韦的药物的核苷核心。Pharmasset科学家对其磷酸化谱的后续分析表明,将其转化为相应的单磷酸前药将规避激酶阻断,并使其成为有效的丙型肝炎聚合酶抑制剂。第三个案例研究描述了DRIVE(埃默里药物创新风险投资公司)/EIDD(埃默里药物开发研究所)的形成,这是为了规避进行学术药物发现和开发的意外障碍而创建的。虽然DRIVE/EIDD是一家全资公司,埃默里大学的非营利性子公司,它包含许多属性,使其能够比典型的学术实验室更灵活地运行。有一个经验丰富的药物开发团队,没有股东分散他们的注意力,DRIVE/EIDD能够将注意力集中在药物开发上,以解决全球关注的病毒性疾病。特别是,他们的战略,以确定和开发抗病毒剂对多种单链RNA病毒产生活性,一个广泛活跃的,获得治疗SARS-CoV-2感染的紧急使用许可的口服药物(即,COVID-19)。
    A new drug can have its origin in either pharma, biotech or academia. In general, discovery scientists working in pharma and biotech are advantaged over their academic counterparts and the relative advantages and disadvantages associated are discussed in depth. Against all odds, an increasing number of important drugs have had their origins in academia. This article reports three case studies from the Liotta Research Group (LRG), which explores the special circumstances that allowed these drug development campaigns to be successful. The first involves the antiretroviral agent, emtricitabine. In this case efficient synthetic methodology, developed in the LRG, coupled with some key university and commercial sector partnerships, enabled a group of academic collaborators to discover and develop a highly effective HIV reverse transcriptase inhibitor. The second case study involves the discovery and development of the breakthrough hepatitis C drug, sofosbuvir. Based on key input from Professors Schinazi and Liotta at Emory University, scientists at the Emory startup, Pharmasset, identified the nucleoside core of the drug that would become sofosbuvir. Subsequent analysis of its phosphorylation profile by Pharmasset scientists suggested that converting it to its corresponding monophosphate prodrug would circumvent a kinase block and enable it to be an effective hepatitis C polymerase inhibitor. The third case study describes the formation of DRIVE (Drug Innovation Ventures at Emory)/EIDD (Emory Institute for Drug Development), which were created to circumvent unintended impediments for carrying out academic drug discovery and development. Although DRIVE/EIDD is a wholly-owned, not-for-profit subsidiary of Emory University, it contains many attributes that enables it to operate much more nimbly than a typical academic laboratory. With an experienced drug development team and no shareholders to distract them, DRIVE/EIDD was able to focus its attention of the development of drugs to address viral diseases of global concern. In particular, their strategy to identify and develop an antiviral agent active against multiple single-stranded RNA viruses led to molnupiravir, a broadly active, oral drug that received Emergency Use Authorization for the treatment of SARS-CoV-2 infections (i.e., COVID-19).
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  • 文章类型: Journal Article
    背景:由于因素,HIV阳性患者的合并症发生率高于普通人群,如HIV相关的慢性炎症。对于长期随访中病毒学抑制后的低CD4淋巴细胞计数是否会增加合并症的风险,尚无共识。这项研究评估了在高效抗逆转录病毒治疗后的前5年病毒学抑制期间CD4淋巴细胞计数与合并症发生率之间的关联。
    方法:我们对哥伦比亚2002年至2016年在HIV项目中实现病毒学抑制的HIV阳性成人进行了一项队列研究。使用广义方程估计模型来估计CD4淋巴细胞计数与合并症发生率之间的关联。
    结果:921名HIV阳性病毒学抑制患者完成了至少1年的随访期。在最多5年的随访中,我们发现了71例合并症;41例(59%)是定义为艾滋病的合并症,其中19例(46%)发生在第一学期。诊断出30例非艾滋病定义的合并症。我们没有发现CD4淋巴细胞计数与合并症发生率之间的任何关联(CD4201-499细胞/μL与CD4≤200细胞/μL的OR0.92,CI95%0.45-1.91,CD4≥500个细胞/µL与CD4≤200个细胞/µL的OR0.55,95%CI0.21-1.44)。
    结论:在病毒学抑制患者中,CD4淋巴细胞计数与确定为AIDS或非确定为AIDS的合并症的发生率之间未发现关联。需要进一步的研究来评估该人群合并症的风险,以设计旨在改善其预后的干预措施。
    BACKGROUND: The incidence of comorbidities is higher in HIV-positive patients than in the general population due to factors, such as HIV-related chronic inflammation. There is no consensus on whether a low CD4 lymphocyte count after virological suppression at long-term follow-up increases the risk of comorbidities. This study evaluates the association between CD4 lymphocyte count and the incidence of comorbidities during the first 5 years of virological suppression after highly active antiretroviral treatment.
    METHODS: We conducted a cohort study of HIV-positive adults who achieved virological suppression in an HIV program between 2002 and 2016 in Colombia. A generalized equation estimation model was used to estimate the association between CD4 lymphocyte count and the incidence of comorbidities.
    RESULTS: A follow-up period of at least 1 year was completed in 921 HIV-positive patients with virological suppression. We found 71 comorbidities during a maximum of 5 years of follow-up; 41 (59%) were AIDS-defining comorbidities and 19 (46%) of them occurred during the first semester. Thirty cases of non-AIDS- defining comorbidities were diagnosed.We did not find any association between CD4 lymphocyte count and the incidence of comorbidities (OR 0.92, CI 95% 0.45 -1.91 for CD4 201-499 cells/µL vs CD4 ≤200 cells/µL, and OR 0.55, 95% CI 0.21-1.44 for CD4 ≥500 cells/µL vs CD4 ≤200 cells/µL).
    CONCLUSIONS: No association was found between CD4 lymphocyte count and the incidence of AIDS-defining or non-AIDS-defining comorbidities in patients with virological suppression. Further studies are needed to assess the risk of comorbidities in this population to design interventions aimed at improving their prognosis.
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  • 文章类型: Editorial
    丙型肝炎病毒(HCV)/人类免疫缺陷病毒(HIV)合并感染仍涉及全球230万患者,估计有3770万HIV感染者。根据世界卫生组织。艾滋病毒感染者(PLWH)受丙型肝炎病毒影响大六倍,与艾滋病毒阴性者相比;注射吸毒者和男男性行为者的患病率更高:在这种情况下,通过性接触传播HCV的风险可能因艾滋病毒感染而增加。这些患者的慢性肝炎发病率很高,如果不及时治疗,则发展为终末期肝病和肝细胞癌(HCC)HIV感染会增加母婴垂直传播HCV的风险。目前还没有针对这两种感染的疫苗接种。HIV和HCV感染之间存在相互作用。目前,HCV的治疗基于直接作用抗病毒药物(DAAs),HCV治疗在限制肝病进展和降低单感染和共感染个体HCC发展的风险中起关键作用。尤其是在纤维化的早期阶段使用时,降低肝病死亡率和发病率。因为在12周的持续病毒学应答率观察到在PLWH后HCV根除,AASLD修改了其简化的HCV治疗算法,将HIV感染者也包括在内.HCV根除可以确定血脂异常,因为HCV会促进血清脂质分布的变化,并可能影响脂质代谢。除了这些对脂质分布的明显有害影响,DAA在HCV/HIV患者中的疗效需要考虑其对肝功能改善介导的糖代谢的影响.本社论的目的是描述PLWH中HCV治疗的进展。
    Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
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  • 文章类型: Journal Article
    本研究旨在调查HIV(PLWH)感染者中估计的脉搏波速度(ePWV)与代谢综合征(MetS)之间的关系,提出了一种新颖方便的预测因子,用于PLWH中MetS的早期检测。
    共注册了485个PLWH。根据估计的脉搏波速度(ePWV)水平将这些参与者分为两组。收集人口统计学和临床数据以研究ePWV与MetS之间的相关性。
    根据10m/s的ePWV截止值,将485PLWH的队列分为高ePWV和低ePWV组。我们观察到MetS成分包括甘油三酯(TG,P<0.05),HDL胆固醇(HDL-C,P<0.01),收缩压(SBP,P<0.001),舒张压(DBP,P<0.05),和空腹血糖(FPG,两组之间P<0.001)。此外,我们采用受试者工作特征(ROC)曲线来证明ePWV作为PLWH中MetS的预测指标的有效性(AUC=0.739,P<0.001).根据ROC曲线,ePWV的最佳截止值为7.4m/s,诊断PLWH中MetS的敏感性和特异性分别为79.03%和64.07%,分别。尽管与传统的截止值相比,7.4m/s的截止值增加了假阳性率,它大大降低了漏诊率,用MetS有效识别79.03%的PLWH。
    ePWV是一种非侵入性且方便的新型生物标志物,具有PLWH中MetS的预测能力。
    UNASSIGNED: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH.
    UNASSIGNED: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS.
    UNASSIGNED: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS.
    UNASSIGNED: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.
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  • 文章类型: Journal Article
    背景:与男性发生性关系的男性(MSM),尤其是那些艾滋病毒携带者,患肛门癌的风险增加。其前体的患病率和发生率,肛门高级别鳞状上皮内病变(HSILs),在急性HIV感染期间开始抗逆转录病毒治疗的MSM中,还有待探讨.
    方法:曼谷急性HIV感染队列的参与者,泰国,谁同意参加这项研究,已注册。所有参与者在急性HIV感染期间被诊断并开始抗逆转录病毒治疗。人乳头瘤病毒(HPV)基因分型和高分辨率肛门镜检查,随后进行肛门活检,在基线和6个月访问时进行。
    结果:共有89名MSM和4名变性女性被纳入分析。入学时的中位年龄为26岁。组织学肛门HSIL的基线患病率为11.8%。共随访147.0人年,初次组织学肛门HSIL的发生率为19.7/100人年.与肛门HSIL事件相关的因素是肛门HPV16(调整后的危险比[aHR]4.33,95%CI1.03-18.18),肛门HPV18/45(aHR6.82,95%CI1.57-29.51),其他肛门高危型HPV(aHR4.23,95%CI1.27-14.14),梅毒感染(aHR4.67,95%CI1.10-19.90)和CD4计数<350细胞/mm3(aHR3.09,95%CI1.28-7.48)。
    结论:在急性HIV感染期间启动抗逆转录病毒治疗,我们发现,在男男性行为者和变性女性中,肛交HSIL的患病率与无HIV者相似.随后的肛门HSIL发生率,虽然低于那些长期感染艾滋病毒的人,仍然高于没有艾滋病毒的人。肛门HSIL的筛查和管理应该是所有MSM长期HIV护理的关键部分。
    BACKGROUND: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored.
    METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits.
    RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48).
    CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.
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  • 文章类型: Journal Article
    脂肪营养不良综合征是一种医学病症,其特征在于缺乏脂肪组织而没有任何潜在的饥饿或大分子分解。在艾滋病患者中,使用高活性抗逆转录病毒疗法(HAART)可导致获得性脂肪营养不良,艾滋病毒/艾滋病患者的患病率为10%至83%。旨在回顾当前对AIDS患者与脂肪营养不良相关的生物学描述和挑战的理解。在PubMed中搜索了以英语发表的相关文章,谷歌学者,和Google。用于搜索的关键词是:脂肪营养不良,脂肪营养不良和艾滋病毒,ART和脂肪营养不良,艾滋病毒治疗,代谢综合征和HIV。对于符合审查客观标准的文章,阅读了具有完整摘要信息的文章,然后文章的全文被访问和使用。文献表明,发生脂肪营养不良的患者以胰岛素异常为特征,肥胖,糖尿病,血脂异常,脂肪肝,和卵巢功能障碍。已知人体测量随着脂肪营养不良而显着改变。患有丙型肝炎病毒的HIV患者,乙型肝炎病毒,服用蛋白酶抑制剂的人,正在改变治疗或治疗持续时间,女性是脂肪营养不良的常见危险因素。在与脂肪营养不良相关的HIV患者中看到的代谢综合征可以进一步复杂化不同的不良健康影响,并且如果不治疗,可以导致增加的发病率和死亡率。现有的研究已经成功地确定了艾滋病患者由于脂肪营养不良而面临的几个挑战,包括低自尊,生活质量受损,治疗依从性差。然而,至关重要的是要承认可能还有许多其他挑战有待发现,强调需要进一步研究。建议管理血脂异常,治疗糖尿病,改变生活方式,改善人体测量学测量对于阻止与脂肪营养不良相关的进一步并发症具有关键作用。
    Lipodystrophy syndrome is a medical condition characterized by the absence of adipose tissue without any underlying starvation or macromolecule breakdown. In HIV AIDS patients, the use of highly active antiretroviral therapy (HAART) can lead to an acquired form of lipodystrophy, with a prevalence ranging from 10% to 83% among HIV AIDS patients. It was aimed to review the current understanding of biological depiction and challenges related to lipodystrophy in AIDS patients. Relevant articles published in the English language were searched in PubMed, Google Scholar, and Google. Keywords used for the search were: lipodystrophy, lipodystrophy and HIV, ART and lipodystrophy, HIV treatment, metabolic syndrome and HIV. Articles with full abstract information were read for those that met the objective criteria of the review, then full text of the articles was accessed and used. It was revealed by the literature that patients who developed lipodystrophy are characterized by insulin abnormality, obesity, diabetes mellitus, dyslipidemia, fatty liver disease, and ovarian dysfunction. Anthropometric measurements have been known to change significantly with lipodystrophy. HIV patients suffering from hepatitis C virus, hepatitis B virus, who take a protease inhibitor, are changing treatment or duration of treatment, and are women are the common risk factors for lipodystrophy. The metabolic syndrome seen in HIV patients associated with lipodystrophy can further be complicated to different adverse health effects and can result in increased morbidity and mortality rate if not treated. Existing studies have successfully identified several challenges faced by HIV AIDS patients due to lipodystrophy, including low self-esteem, compromised quality of life, and poor treatment adherence. However, it is crucial to acknowledge that there may be numerous other challenges that have yet to be discovered, emphasizing the need for further studies. It is recommended that managing dyslipidemia, treating diabetes mellitus, modifying lifestyle, and improving the anthropometric measurements have crucial roles to halt further complications associated with lipodystrophy.
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  • 文章类型: Systematic Review
    抗逆转录病毒疗法(ART)的引入显着延长了人类免疫缺陷病毒(PLWH)患者的寿命。然而,这种药物方案的持续使用也与一系列代谢异常有关,包括肾毒性,这可能导致肾脏疾病的发展。在这项研究中,我们回顾了在PLWH中检查肾脏疾病的研究,这些研究来自电子数据库,如PubMed/MEDLINE,Scopus,和谷歌学者,以及灰色文学。这些临床研究数据的叙述性综合表明,在ART的PLWH中,胱抑素C的血清水平保持不变或不受影响,而基于肌酐的肾小球滤过率(GFR)波动。事实上,一些纳入的研究表明,基于肌酐的GFR在PLWH服用含有富马酸替诺福韦酯的ART中增加,也许表明使用基于胱抑素C和肌酐的GFR对于监测PLWH中肾脏疾病的发展至关重要.本研究中总结的临床数据表明替诺福韦为基础的ART方案在引起肾小管损伤的潜在有害影响,同时强调了基于dolutegravir的ART对改善PLWH肾功能的可能有益作用。然而,总结的文献仍然有限,同时还需要进一步的临床研究来深入了解胱抑素C作为PLWH肾脏疾病生物标志物的潜在用途.
    The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.
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  • 文章类型: Journal Article
    尽管高活性抗逆转录病毒疗法(HAART)在抑制病毒方面的疗效有所提高,新出现的证据表明,艾滋病毒感染者(PLWH)的非传染性疾病负担增加。免疫激活和持续升高的炎症水平与PLWH的内皮功能障碍有关。可能导致心血管疾病(CVD)的发展。这里,电子搜索数据库,包括PubMed,谷歌学者,科克伦图书馆,和ScienceDirect用于检索关于在HAART的PLWH中内皮功能标志物与CVD相关结局之间任何关联的科学证据。使用Downs和Black检查表对提取的数据进行质量评估。大多数(60%)的结果表明在HAART的PLWH中存在内皮功能障碍,这主要是通过减少流量介导的扩张和升高的ICAM-1,VCAM-1和P-选择素等粘附分子的血清标记。总结的证据表明,在HAART的PLWH中,内皮功能障碍的标志物持续升高与促炎状态之间存在关联。只有少数研究报道了PLWH在HAART上改善的内皮功能标志物,虽然有限的证据证明内皮功能障碍与CVD风险有关,这可以归因于HAART的治疗效果。本系统评价中纳入了证据质量相对较高的有限研究。总之,本综述的结果为今后的研究奠定了重要的基础,甚至是荟萃分析,这将提高对PLWH对HAART的CVD负担的影响因素的理解。
    Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.
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  • 文章类型: Meta-Analysis
    炎症的病理后果在人类免疫缺陷病毒(PLWH)患者中持续存在,无论高活性抗逆转录病毒治疗(HAART)的积极结果如何。目前的系统评价和荟萃分析旨在了解和探讨高敏C反应蛋白(hs-CRP)和其他心血管疾病(CVD)危险因素的水平,包括HAART的PLWH中的血脂状况。主要电子数据库,包括PubMed,Scopus,和WebofScience进行检索,以检索有关HAARTPLWH中hs-CRP水平的相关全球文献报告。共有22项研究的参与者平均年龄为40岁,符合这项系统评价和荟萃分析的条件。大部分纳入的研究来自非洲(n=11),美国(n=6)欧洲(n=5)。我们的系统评价显示,大多数研究报告与对照组相比,在HAART治疗的PLWH中hs-CRP水平升高(PLWH不在HAART治疗或无HIV治疗),尤其是来自非洲的研究。这得到了荟萃分析的支持,该荟萃分析显示,与未使用HAART的PLWH相比,HAART的PLWH中的hs-CRP水平显着升高(标准化平均差异[SMD]=0.56;95%CI=0.10-1.01,z=2.41;p=0.02)或没有HIV的患者(SMD=1.19;95%CI=0.76-1.63,z=5.35;p<如果脂质分布,作为心血管疾病风险的主要预测因子,与不接受HAART的PLWH和HIV阴性参与者相比,接受HAART的PLWH也受损。总之,hs-CRP和血脂水平升高在HAART的PLWH中普遍存在,这可能会增加CVD并发症的风险,尤其是那些生活在非洲的人。然而,在更大规模的人群研究中,需要更多的证据来证实这些结局,并揭示HAART诱导的PLWH中hs-CRP水平调节的任何可能的临床意义.
    The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10‑1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76‑1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.
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