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CSL112 and HDL function hypothesis - a never-ending wait. CSL112 和高密度脂蛋白功能假说--永无止境的等待。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-07-15 DOI: 10.1080/17512433.2024.2378763
Muhammad Adnan Zaman, Sidra Kalsoom, Warsha Koran
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引用次数: 0
Clinical considerations when switching antiretroviral therapy. 转换抗逆转录病毒疗法时的临床考虑因素。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-06-17 DOI: 10.1080/17512433.2024.2365826
Analuz Fernández, Arkaitz Imaz

Introduction: Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance.

Areas covered: The authors reviewed clinical trials and cohort studies providing evidence of benefits and risks of current antiretroviral (ARV) drugs as switching options for PLWH in various scenarios. The literature search included clinical trials, meta-analyses, observational studies, and review articles in English published after 2000, and current HIV treatment guidelines in English and Spanish as of February 2024.

Expert opinion: New ARV drugs offer advantages in efficacy and safety over previous options but may also have adverse effects. Second-generation integrase inhibitors and tenofovir alafenamide show benefits as switching options in various scenarios, though more research is needed on potential weight gain and metabolic issues. Injectable long-acting ART is promising for switching strategies, but finding the optimal combination of new drugs remains challenging.

导言:抗逆转录病毒疗法(ART)可以通过具有高耐药性屏障、良好的安全性和新型给药途径的简单制剂实现个性化治疗。转换疗法已成为解决药物毒性和相互作用、提高依从性和便利性的关键临床策略。这一策略旨在提高生活质量和长期疗效,即使是对具有多种并发症、既往病毒学失败和耐药性的艾滋病病毒感染者(PLWH)等具有挑战性的病例也是如此:作者对临床试验和队列研究进行了综述,这些研究提供了当前抗逆转录病毒(ARV)药物在不同情况下作为 PLWH 转药选择的益处和风险证据。文献检索包括 2000 年之后发表的英文临床试验、荟萃分析、观察性研究和综述文章,以及截至 2024 年 2 月的英文和西班牙文现行 HIV 治疗指南:新的抗逆转录病毒药物在疗效和安全性方面均优于以往的选择,但也可能存在不良反应。第二代整合酶抑制剂和替诺福韦-阿拉非那胺显示出在各种情况下作为转换方案的优势,但还需要对潜在的体重增加和代谢问题进行更多研究。注射用长效抗逆转录病毒疗法在转换策略中大有可为,但找到新药的最佳组合仍具有挑战性。
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引用次数: 0
Antiretroviral therapy response: exploring the potential influence of SARS-CoV-2. 抗逆转录病毒疗法反应:探索 SARS-CoV-2 的潜在影响。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-02-28 DOI: 10.1080/17512433.2024.2322984
Ahmad Z Al Meslamani
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引用次数: 0
Therapeutic drug monitoring of antiretroviral therapy: current progresses and future directions. 抗逆转录病毒疗法的治疗药物监测:当前进展和未来方向。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-06-04 DOI: 10.1080/17512433.2024.2363847
Dario Cattaneo, Cristina Gervasoni

Introduction: The treatment of HIV infection has been revolutionized in recent years thanks to the advent of dual antiretroviral regimens, administered orally or as long-acting injectable formulations. Here, we provide an update on the usefulness of therapeutic drug monitoring (TDM) of antiretroviral drugs to optimize the management of people with HIV (PWH) in the current scenario.

Areas covered: A MEDLINE PubMed search for articles published between January 2014 and January 2024 was completed matching the terms HIV, antiretrovirals and TDM. Moreover, additional studies were identified from the reference list of retrieved articles.

Expert opinion: Available antiretroviral treatments achieve a response rate of 90%-95%, making the routine TDM of antiretroviral drugs of limited clinical value. However, there are still some important applications of TDM in selected clinical conditions, such as assessing patient compliance or suspected drug-drug interactions (DDIs). Indeed, we are increasingly having to deal with polypharmacy and DDIs in the context of an aging patient with comorbidities that may potentially alter the pharmacokinetics of antiretroviral drugs. Finally, the role of pharmacogenetics, which is closely related to TDM, in influencing both the disposition of antiretrovirals and the course of DDIs should also be considered.

导言:近年来,由于出现了口服或长效注射的双重抗逆转录病毒疗法,艾滋病病毒感染的治疗发生了革命性的变化。在此,我们将介绍抗逆转录病毒药物治疗药物监测(TDM)的最新进展,以优化当前情况下对艾滋病病毒感染者(PWH)的管理:对 2014 年 1 月至 2024 年 1 月期间发表的文章进行了 MEDLINE PubMed 搜索,搜索关键词为 HIV、抗逆转录病毒药物、TDM。此外,还从检索文章的参考文献列表中发现了其他研究:专家意见:现有的抗逆转录病毒治疗可达到 90%-95% 的应答率,因此抗逆转录病毒药物的常规 TDM 临床价值有限。不过,TDM 在某些特定的临床条件下仍有一些重要的应用,如评估患者的依从性或可疑的药物相互作用(DDI)。事实上,我们越来越多地需要在高龄患者合并症的背景下处理多重用药和 DDIs 问题,这些合并症可能会改变抗逆转录病毒药物的药代动力学。最后,还应考虑与药物代谢动力学密切相关的药物遗传学在影响抗逆转录病毒药物的处置和 DDIs 过程中的作用。
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引用次数: 0
Considerations when prescribing opioid agonist therapies for people living with HIV. 为艾滋病毒感染者开具阿片类激动剂疗法处方时的注意事项。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-07-04 DOI: 10.1080/17512433.2024.2375448
Adati Tarfa, Audun J Lier, Sheela V Shenoi, Sandra A Springer

Introduction: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH).

Areas covered: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management.

Expert opinion: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.

导言:治疗阿片类药物使用障碍(MOUD)的药物包括阿片类药物激动剂疗法(OAT)(丁丙诺啡和美沙酮)和阿片类药物拮抗剂(缓释纳曲酮)。所有形式的 MOUD 都能改善阿片类药物使用障碍(OUD)和艾滋病的治疗效果。然而,针对艾滋病毒和阿片类药物使用障碍的整合服务仍然不足。在获得 MOUD 方面持续存在的障碍凸显了在治疗艾滋病病毒感染者(PWH)的 OUD 时解决药物公平性问题的紧迫性:在这篇综述文章中,我们特别关注艾滋病感染者中的 OAT,因为它是最常用的 MOUD 形式。具体而言,我们描述了艾滋病和 OUD 服务的交叉点,强调通过提供全面的艾滋病和 OUD 筛查、检测和治疗,将其纳入美国遏制艾滋病流行(EHE)计划。我们确定了 OAT 与抗逆转录病毒疗法(ART)之间潜在的药物相互作用,解决了 OAT 获取方面的差异,并介绍了丁丙诺啡长效制剂、抗逆转录病毒疗法和暴露前预防对改善 HIV 预防和治疗以及 OUD 管理的实际益处:专家意见:要优化公共卫生机构的 OUD 治疗效果,就必须认真关注 OUD 的诊断、OUD 治疗的启动以及药物的保留。创新的医疗保健服务方式(如流动药房)可以将 OUD 和 HIV 治疗结合起来,并惠及服务不足的人群。
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引用次数: 0
A preliminary study on plasma concentration, short-term efficacy, and safety profile of dolutegravir in Chinese people with HIV. 关于多鲁曲韦在中国艾滋病病毒感染者中的血浆浓度、短期疗效和安全性的初步研究。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-01-26 DOI: 10.1080/17512433.2024.2308664
Dongsheng Li, Ran Xiao, Qiang Fu, Xiaojing Song, Yang Han, Xiaoli Du, Taisheng Li

Background: This study examined the plasma concentration, clinical efficacy, and safety of dolutegravir (DTG) in Chinese people with HIV (PWH).

Methods: In this observational study, HIV-positive individuals on DTG-based regimens for at least 6 months were included. Plasma DTG concentrations were measured 1 month after initiating treatment. Viral loads (VL) and CD4+ T cell counts were evaluated at baseline and after 1 and 6 months of therapy. High-performance liquid chromatography was used for measuring DTG concentrations, polymerase chain reaction for VL, and flow cytometry for CD4+ T cell counts. Safety assessments included monitoring liver enzymes, serum creatinine estimated glomerular filtration rate, and adverse reactions.

Results: Eighty-two Chinese PWH were enrolled. Average VL decreased significantly from baseline by 3.1 log at 1 month and 3.5 log at 6 months. CD4+ T cell counts increased from 273 cells/mm3 at baseline to 378 cells/mm3 and 446 cells/mm3 after 1 and 6 months, respectively. Seventy-five percent achieved undetectable VLs (<20 copies/mL) by 6 months. Cmax and Cτ were 4.63 and 1.98 μg/mL, respectively. The safety profile was favorable with only 4.88% experiencing transient dizziness.

Conclusion: Preliminary findings suggest higher DTG plasma concentrations in Chinese PWH compared to Western populations, with promising short-term efficacy and safety.

研究背景本研究探讨了多罗替拉韦(DTG)在中国艾滋病病毒感染者(PWH)中的血浆浓度、临床疗效和安全性:在这项观察性研究中,纳入了接受基于 DTG 方案治疗至少 6 个月的 HIV 阳性者。在开始治疗一个月后测量血浆中的DTG浓度。病毒载量(VL)和 CD4+ T 细胞计数分别在基线和治疗 1 个月和 6 个月后进行评估。高效液相色谱法用于测量 DTG 浓度,聚合酶链反应用于测量 VL,流式细胞术用于测量 CD4+ T 细胞计数。安全性评估包括监测肝酶、血清肌酐、肾小球滤过率和不良反应:结果:82 名中国肺结核患者接受了治疗。一个月后,平均 VL 比基线明显下降了 3.1 log,六个月后下降了 3.5 log。CD4+ T细胞计数从基线时的273个细胞/立方毫米分别增加到一个月后的378个细胞/立方毫米和六个月后的446个细胞/立方毫米。75%的患者检测不到VL(最大值和Cτ值分别为4.63和1.98微克/毫升)。安全性状况良好,仅有4.88%的患者出现短暂头晕:初步研究结果表明,与西方人群相比,中国PWH的DTG血浆浓度较高,短期疗效和安全性良好。
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引用次数: 0
An update on drug-drug interactions in older adults living with human immunodeficiency virus (HIV). 关于感染人类免疫缺陷病毒(HIV)的老年人药物相互作用的最新情况。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-06-30 DOI: 10.1080/17512433.2024.2350968
Rebecca Y Linfield, Nancy N Nguyen, Olivia H Laprade, Mark Holodniy, Aarthi Chary

Introduction: People with HIV are living longer due to advances in antiretroviral therapy. With improved life expectancy comes an increased lifetime risk of comorbid conditions - such as cardiovascular disease and cancer - and polypharmacy. Older adults, particularly those living with HIV, are more vulnerable to drug interactions and adverse effects, resulting in negative health outcomes.

Area covered: Antiretrovirals are involved in many potential drug interactions with medications used to treat common comorbidities and geriatric conditions in an aging population of people with HIV. We review the mechanisms and management of significant drug-drug interactions involving antiretroviral medications and non-antiretroviral medications commonly used among older people living with HIV. The management of these interactions may require dose adjustments, medication switches to alternatives, enhanced monitoring, and considerations of patient- and disease-specific factors.

Expert opinion: Clinicians managing comorbid conditions among older people with HIV must be particularly vigilant to side effect profiles, drug-drug interactions, pill burden, and cost when optimizing treatment. To support healthier aging among people living with HIV, there is a growing need for antiretroviral stewardship, multidisciplinary care models, and advances that promote insight into the correlations between an individual, their conditions, and their medications.

导言:由于抗逆转录病毒疗法的进步,艾滋病毒感染者的寿命越来越长。随着预期寿命的延长,一生中患合并症(如心血管疾病和癌症)和多种药物的风险也随之增加。老年人,尤其是艾滋病病毒感染者,更容易受到药物相互作用和不良反应的影响,从而导致不良的健康后果:抗逆转录病毒药物与用于治疗老年艾滋病病毒感染者常见合并症和老年病的药物之间存在许多潜在的药物相互作用。我们回顾了老年艾滋病病毒感染者常用的抗逆转录病毒药物和非抗逆转录病毒药物之间重大药物相互作用的机制和管理。处理这些相互作用可能需要调整剂量、改用替代药物、加强监测以及考虑患者和疾病的特异性因素:专家意见:管理老年艾滋病感染者合并症的临床医生在优化治疗时,必须对副作用、药物间相互作用、药片负担和成本保持特别警惕。为了支持艾滋病病毒感染者更健康地步入老年,越来越需要抗逆转录病毒药物管理、多学科护理模式,以及促进对个人、病情和药物之间相关性的深入了解。
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引用次数: 0
Clinical considerations and pharmacokinetic interactions between HIV and tuberculosis therapeutics. 临床考虑因素和艾滋病毒与结核病治疗药物之间的药代动力学相互作用。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-02-14 DOI: 10.1080/17512433.2024.2317954
Nicole F Maranchick, Awewura Kwara, Charles A Peloquin

Introduction: Tuberculosis (TB) is a leading infectious disease cause of mortality worldwide, especially for people living with human immunodeficiency virus (PLWH). Treating TB in PLWH can be challenging due to numerous drug interactions.

Areas covered: This review discusses drug interactions between antitubercular and antiretroviral drugs. Due to its clinical importance, initiation of antiretroviral therapy in patients requiring TB treatment is discussed. Special focus is placed on the rifamycin class, as it accounts for the majority of interactions. Clinically relevant guidance is provided on how to manage these interactions. An additional section on utilizing therapeutic drug monitoring (TDM) to optimize drug exposure and minimize toxicities is included.

Expert opinion: Antitubercular and antiretroviral coadministration can be successfully managed. TDM can be used to optimize drug exposure and minimize toxicity risk. As new TB and HIV drugs are discovered, additional research will be needed to assess for clinically relevant drug interactions.

简介结核病(TB)是导致全球死亡的主要传染病,尤其是对人类免疫缺陷病毒感染者(PLWH)而言。由于多种药物相互作用,治疗 PLWH 中的结核病具有挑战性:本综述讨论了抗结核药物与抗逆转录病毒药物之间的相互作用。由于其临床重要性,本文讨论了需要接受结核病治疗的患者开始抗逆转录病毒治疗的问题。本文特别关注利福霉素类药物,因为该类药物占相互作用的大多数。就如何处理这些相互作用提供了临床相关指导。此外,还加入了关于利用治疗药物监测(TDM)优化药物暴露和减少毒性的章节:专家观点:抗结核药物和抗逆转录病毒药物的联合用药可以成功控制。专家观点:抗结核药物和抗逆转录病毒药物的联合用药可成功管理,TDM 可用于优化药物暴露和降低毒性风险。随着结核病和艾滋病新药的发现,需要开展更多的研究,以评估与临床相关的药物相互作用。
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引用次数: 0
What is novel in the clinical management of pemphigus vulgaris? 寻常型天疱疮的临床治疗有何新意?
IF 4.4 3区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-05-01 Epub Date: 2024-05-12 DOI: 10.1080/17512433.2024.2350943
Ahmad Vafaeian, Hamidreza Mahmoudi, Maryam Daneshpazhooh

Introduction: Pemphigus, an uncommon autoimmune blistering disorder affecting the skin and mucous membranes, currently with mortality primarily attributed to adverse reactions resulting from treatment protocols. Additionally, the existing treatments exhibit a notable recurrence rate. The high incidence of relapse and the considerable adverse effects associated with treatment underscore the imperative to explore safer and more effective therapeutic approaches. Numerous potential therapeutic targets have demonstrated promising outcomes in trials or preliminary research stages. These encompass anti-CD-20 agents, anti-CD-25 agents, TNF-α inhibition, FAS Ligand Inhibition, FcRn inhibition, BAFF inhibition, Bruton's tyrosine kinase (BTK) inhibition, CAAR T Cells, JAK inhibition, mTOR inhibition, abatacept, IL-4 inhibition, IL-17 inhibition, IL-6 inhibition, polyclonal Regulatory T Cells, and autologous hematopoietic stem cell transplantation.

Areas covered: The most significant studies regarding the impact and efficacy of the mentioned treatments on pemphigus were meticulously curated through a comprehensive search conducted on the PubMed database. Moreover, the investigations of interest cited in these studies were also integrated.

Expert opinion: The efficacy and safety profiles of the other treatments under discussion do not exhibit the same level of robustness as anti-CD20 therapy, which is anticipated to endure as a critical element in pemphigus treatment well into the foreseeable future.

简介丘疹性荨麻疹是一种影响皮肤和粘膜的不常见自身免疫性水疱病,目前的死亡率主要归因于治疗方案导致的不良反应。此外,现有治疗方法的复发率也很高。高复发率和与治疗相关的严重不良反应突出表明,探索更安全、更有效的治疗方法势在必行。在试验或初步研究阶段,许多潜在的治疗靶点已显示出良好的疗效。这些靶点包括抗CD-20药物、抗CD-25药物、TNF-α抑制剂、FAS配体抑制剂、FcRn抑制剂、BAFF抑制剂、布鲁顿酪氨酸激酶(BTK)抑制剂、CAAR T细胞、JAK抑制剂、mTOR抑制剂、阿巴西普、IL-4抑制剂、IL-17抑制剂、IL-6抑制剂、多克隆调节性T细胞以及自体造血干细胞移植:通过在 PubMed 数据库中进行全面搜索,我们精心挑选了有关上述治疗方法对丘疹性荨麻疹的影响和疗效的最重要研究。此外,还整合了这些研究中引用的相关调查:专家意见:所讨论的其他治疗方法的疗效和安全性并不像抗 CD20 疗法那样稳健,预计在可预见的未来,抗 CD20 疗法仍将是治疗丘疹性荨麻疹的关键因素。
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引用次数: 0
Therapeutic drug monitoring in kidney and liver transplantation: current advances and future directions. 肝肾移植中的治疗药物监测:当前进展与未来方向。
IF 4.4 3区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-05-01 Epub Date: 2024-05-16 DOI: 10.1080/17512433.2024.2354276
Béni Ntobe-Bunkete, Florian Lemaitre

Introduction: Immunosuppressive drugs (ISD) present a narrow therapeutic window and extremely high inter- and intra-individual pharmacokinetic variability, which complicates their use in solid organ transplant recipients. In order to find a narrow appropriate equilibrium for each patient with the aim of maintaining clinical efficacy and reducing the risk of adverse drug reactions, a complex both clinical and biological monitoring is required, in particular through the use of therapeutic drug monitoring (TDM).

Area covered: This review provides an overview of the available information on the relationship between exposure to immunosuppressive drugs and their efficacy and/or toxicity in kidney and liver transplantation. The aim of the review is to describe the pharmacodynamic/pharmacokinetic relationship that exists for immunosuppressive drugs, to summarize the studies that assess the value of TDM for these drugs in clinical practice, and to present the target and monitoring strategies aimed at optimizing patient immunosuppression, which could help to take a step forward in the field of solid organ transplant patient care.

Expert opinion: To improve the care of transplant patients, several TDM innovations can be pursued by investigators. Among these, the development of microsampling methods for TDM or the combination of pharmacodynamic biomarkers with ISD exposure measurements appear to be relevant strategies.

简介免疫抑制剂(ISD)的治疗窗口狭窄,个体间和个体内的药代动力学变异性极高,这使其在实体器官移植受者中的应用变得复杂。为了为每位患者找到合适的狭窄平衡点,以保持临床疗效并降低药物不良反应的风险,需要进行复杂的临床和生物监测,特别是通过使用治疗药物监测(TDM):本综述概述了肾移植和肝移植中免疫抑制剂暴露与其疗效和/或毒性之间关系的现有信息。综述的目的是描述免疫抑制剂的药效学/药代动力学关系,总结评估这些药物的 TDM 在临床实践中的价值的研究,并介绍旨在优化患者免疫抑制的目标和监测策略,这有助于在实体器官移植患者护理领域向前迈进一步:为了改善对移植患者的护理,研究人员可以进行多项 TDM 创新。其中,开发用于 TDM 的微量取样方法或将药效生物标记物与 ISD 暴露测量相结合似乎是相关的策略。
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引用次数: 0
期刊
Expert Review of Clinical Pharmacology
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