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Lenacapavir: a first-in-class HIV-1 capsid inhibitor. Lenacapavir:一流的HIV-1衣壳抑制剂。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1097/COH.0000000000000713
Hadas Dvory-Sobol, Naveed Shaik, Christian Callebaut, Martin S Rhee

Purpose of review: This review summarizes available data for lenacapavir, an investigational first-in-class agent that disrupts functioning of HIV capsid protein across multiple steps in the viral life cycle.

Recent findings: Lenacapavir demonstrated picomolar potency in vitro with no cross resistance to existing antiretroviral classes and potent antiviral activity in persons with HIV-1. In persons with HIV-1, there was no preexisting resistance to lenacapavir regardless of treatment history. Lenacapavir can be administered orally either daily or weekly and subcutaneously up to every 6 months. In heavily treatment-experienced persons with multidrug-resistant HIV-1 and in treatment-naive persons with HIV-1, lenacapavir in combination with other antiretroviral agents led to high rates of virologic suppression and was well tolerated.

Summary: Ongoing studies are evaluating long-acting dosing of lenacapavir for treating HIV-1 in combination with other antiretrovirals and preventing HIV-1 as a single agent.

综述目的:本综述总结了lenacapavir的现有数据,lenacapavir是一种一流的研究性药物,可在病毒生命周期的多个步骤中破坏HIV衣壳蛋白的功能。最近的发现:Lenacapavir在体外显示出皮摩尔效价,对现有抗逆转录病毒类别没有交叉耐药性,并且在HIV-1患者中具有强大的抗病毒活性。在HIV-1患者中,无论治疗史如何,都没有预先存在对lenacapavir的耐药性。Lenacapavir可每日口服或每周口服,并可每6个月皮下注射一次。在有大量治疗经验的耐多药HIV-1患者和未接受治疗的HIV-1患者中,lenacapavir与其他抗逆转录病毒药物联合使用可导致高病毒学抑制率,并且耐受性良好。总结:正在进行的研究正在评估lenacapavir与其他抗逆转录病毒药物联合治疗HIV-1的长效剂量以及作为单一药物预防HIV-1的效果。
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引用次数: 34
Fostemsavir: a first-in-class HIV-1 attachment inhibitor. Fostemsavir:一种一流的HIV-1附着抑制剂。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1097/COH.0000000000000712
Philip M Grant, Michael J Kozal

Purpose of review: Fostemsavir is a recently Food and Drug Administration-approved HIV-1 attachment inhibitor that binds to HIV-1 gp120 and prevents viral attachment to the cellular CD4 receptor. Here, we review the pharmacology, efficacy, tolerability, and resistance profile of fostemsavir.

Recent findings: Fostemsavir is well tolerated and maintains virologic activity in individuals harboring multidrug-resistant HIV-1. In conjunction with optimal background therapy, a majority of heavily treatment-experienced clinical trial participants treated with fostemsavir achieved virologic suppression.

Summary: The approval of fostemsavir represents an important advance for individuals harboring multidrug resistant HIV-1 due to its novel mechanism of action and lack of cross-resistance to other antiretrovirals. Further study will better define the role of resistance testing for fostemsavir and fostemsavir's potential role outside of salvage therapy in heavily treatment-experienced individuals.

综述目的:Fostemsavir是美国食品和药物管理局(fda)最近批准的一种HIV-1附着抑制剂,可结合HIV-1 gp120并阻止病毒附着于细胞CD4受体。在这里,我们回顾了fostemsaver的药理学,疗效,耐受性和耐药概况。最近的研究发现:Fostemsavir在携带多重耐药HIV-1的个体中具有良好的耐受性并保持病毒学活性。与最佳背景治疗相结合,大多数接受过fostemsaver治疗的临床试验参与者获得了病毒学抑制。摘要:由于其新的作用机制和对其他抗逆转录病毒药物缺乏交叉耐药,fostemsavir的批准代表了多药耐药HIV-1个体的重要进展。进一步的研究将更好地确定fostemsavir耐药试验的作用,以及fostemsavir在重度治疗经验个体的挽救治疗之外的潜在作用。
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引用次数: 4
Editorial: New drugs for HIV: quo vadis? 社论:艾滋病新药:现状如何?
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1097/COH.0000000000000710
Charles W Flexner, Angela Kashuba
The WHO estimates that by the beginning of 2021, 27.5 million adults and children were receiving antiretroviral treatment [1]. Many of these individuals are taking a coformulated generic combination of dolutegravir with tenofovir disoproxil fumarate (TDF) and lamivudine (TLD), a daily oral combination that could be thought of as the ‘universal antiretroviral regimen [2]’. In the face of numbers like this, one could easily wonder if there is even a need for new treatments for HIV. Although it has been more than 3 years since this journal reviewed the topic of ‘New Drugs for HIV’, the Table of
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引用次数: 0
A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. 抗逆转录病毒递送的新范例:长效卡博特韦和利匹韦林用于治疗和预防艾滋病毒。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1097/COH.0000000000000708
Sara H Bares, Kimberly K Scarsi

Purpose of review: Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). This review focuses on phase 3 clinical trial results and implementation considerations for these long-acting ART and PrEP strategies.

Recent findings: Long-acting CAB and RPV administered every 4 weeks demonstrated noninferiority to oral ART through week 96 in both the ATLAS and FLAIR studies, whereas ATLAS-2M found similar efficacy through 96 weeks when the long-acting injectable ART was administered every 8 weeks instead of every 4 weeks. For prevention, two phase 3 trials were stopped early due to fewer incident HIV infections in participants receiving long-acting CAB every 8 weeks compared with daily oral tenofovir disoproxil fumarate-emtricitabine for PrEP. The long-acting therapies were well tolerated across all clinical trials.

Summary: Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. Implementation challenges persist, and data are urgently needed in populations who may benefit most from long-acting therapy, including adolescents, pregnant individuals, and those with barriers to medication adherence.

综述目的:Cabotegravir (CAB)和rilpivirine (RPV)是第一个被批准用于病毒学抑制的成人HIV-1患者的长效注射抗逆转录病毒疗法(ART)选择。此外,长效CAB是HIV暴露前预防(PrEP)的一种有前景的药物。本综述侧重于这些长效抗逆转录病毒治疗和PrEP策略的3期临床试验结果和实施考虑。最近的发现:在ATLAS和FLAIR研究中,每4周给药的长效CAB和RPV在96周内与口服ART无劣效性,而ATLAS- 2m在96周内的疗效与每8周给药的长效注射ART相似,而不是每4周给药。在预防方面,由于每8周接受长效CAB的参与者与每天口服富马酸替诺福韦二氧吡酯-恩曲他滨的PrEP相比,HIV感染发生率更低,两项3期试验提前停止。在所有临床试验中,长效疗法耐受性良好。摘要:临床试验结果支持将长效CAB用于HIV PrEP,并将长效CAB和RPV作为口服抗逆转录病毒药物首次病毒学抑制的成人HIV-1患者的切换策略。实施方面的挑战依然存在,迫切需要从长效治疗中获益最多的人群的数据,包括青少年、孕妇和有药物依从性障碍的人群。
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引用次数: 18
Cardiovascular toxicity of contemporary antiretroviral therapy. 当代抗逆转录病毒治疗的心血管毒性。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-11-01 DOI: 10.1097/COH.0000000000000702
Alinda G Vos, W D F Venter

Purpose of review: HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART.

Recent findings: Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern.

Summary: CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART.

综述目的:自20世纪90年代引入抗逆转录病毒疗法(ART)以来,艾滋病毒治疗不断发展。早期的治疗策略,以及在首选的一线抗逆转录病毒治疗中引入整合酶抑制剂,从根本上改变了由HIV感染和抗逆转录病毒治疗引起的心血管副作用。这篇综述提供了当代ART的心血管毒性的最新进展。最近的研究发现:心血管疾病(CVD)的风险,包括心力衰竭,在艾滋病毒感染者(PLWH)中仍然增加。暴露于较老的抗逆转录病毒药物,包括司他夫定和齐多夫定,在停药数年后仍会通过持续改变体脂分布来影响心血管疾病的风险。蛋白酶抑制剂(PI)和依非韦伦有相关的代谢紊乱和增加心血管疾病的风险,尽管使用在世界范围内正在减少。整合酶抑制剂和CCR5拮抗剂似乎具有可忽略不计的即时CVD毒性。包括整合酶抑制剂在内的新型抗逆转录病毒药物的体重增加是一个值得关注的原因。总结:暴露于第一代ART、依非韦伦或PIs的PLWH患者应仔细监测心血管疾病风险。在当前以整合酶抑制剂为基础的抗逆转录病毒治疗快速启动的时代,登记处应该记录抗逆转录病毒治疗的使用和CVD事件,以了解实际的临床风险。
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引用次数: 15
The intersection of drug interactions and adverse reactions in contemporary antiretroviral therapy. 当代抗逆转录病毒治疗中药物相互作用和不良反应的交叉。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-11-01 DOI: 10.1097/COH.0000000000000701
Salin Nhean, Alice Tseng, David Back

Purpose of review: Advances in antiretroviral therapy (ART) have transformed HIV infection into a chronic and manageable condition. The introduction of potent and more tolerable antiretrovirals (ARVs) with favorable pharmacokinetic profiles has changed the prevalence and nature of drug-drug interactions (DDIs). Here, we review the relevance of DDIs in the era of contemporary ART.

Recent findings: Management of DDIs remains an important challenge with modern ART, primarily due to increased polypharmacy in older persons living with HIV. Significant DDIs exist between boosted ARVs or older nonnucleoside reverse transcriptase inhibitors and comedications for chronic comorbidities (e.g., anticoagulants, antiplatelets, statins) or complex conditions (e.g., anticancer agents, immunosuppressants). Newer ARVs such as unboosted integrase inhibitors, doravirine, and fostemsavir have reduced DDI potential, but there are clinically relevant DDIs that warrant consideration. Potential consequences of DDIs include increased toxicity and/or reduced efficacy of ARVs and/or comedications. Management approaches include switching to an ARV with less DDI potential, changing comedications, or altering medication dosage or dosing frequency. Deprescribing strategies can reduce DDIs and polypharmacy, improve adherence, minimize unnecessary adverse effects, and prevent medication-related errors.

Summary: Management of DDIs requires close interdisciplinary collaboration from multiple healthcare disciplines (medicine, nursing, pharmacy) across a spectrum of care (community, outpatient, inpatient).

综述目的:抗逆转录病毒治疗(ART)的进展已将艾滋病毒感染转变为一种可控制的慢性疾病。具有良好药代动力学特征的强效和更耐受的抗逆转录病毒药物(ARVs)的引入改变了药物-药物相互作用(ddi)的患病率和性质。在此,我们回顾ddi在当代艺术时代的相关性。最近的发现:ddi的管理仍然是现代抗逆转录病毒治疗的一个重要挑战,主要是由于老年艾滋病毒感染者的多重用药增加。增强抗逆转录病毒药物或较老的非核苷类逆转录酶抑制剂与慢性合并症药物(如抗凝血剂、抗血小板药物、他汀类药物)或复杂疾病药物(如抗癌药物、免疫抑制剂)之间存在显著的ddi。较新的抗逆转录病毒药物,如未增强的整合酶抑制剂、多拉韦林和fostemsaver,降低了DDI的潜力,但有临床相关的DDI值得考虑。ddi的潜在后果包括抗逆转录病毒药物和/或药物的毒性增加和/或疗效降低。管理方法包括改用DDI潜力较小的抗逆转录病毒药物,更换药物,或改变药物剂量或给药频率。减少处方策略可以减少ddi和多种用药,提高依从性,最大限度地减少不必要的不良反应,并防止药物相关错误。总结:ddi的管理需要来自多个医疗保健学科(医学、护理、药学)的密切跨学科合作,涉及整个护理范围(社区、门诊、住院)。
{"title":"The intersection of drug interactions and adverse reactions in contemporary antiretroviral therapy.","authors":"Salin Nhean,&nbsp;Alice Tseng,&nbsp;David Back","doi":"10.1097/COH.0000000000000701","DOIUrl":"https://doi.org/10.1097/COH.0000000000000701","url":null,"abstract":"<p><strong>Purpose of review: </strong>Advances in antiretroviral therapy (ART) have transformed HIV infection into a chronic and manageable condition. The introduction of potent and more tolerable antiretrovirals (ARVs) with favorable pharmacokinetic profiles has changed the prevalence and nature of drug-drug interactions (DDIs). Here, we review the relevance of DDIs in the era of contemporary ART.</p><p><strong>Recent findings: </strong>Management of DDIs remains an important challenge with modern ART, primarily due to increased polypharmacy in older persons living with HIV. Significant DDIs exist between boosted ARVs or older nonnucleoside reverse transcriptase inhibitors and comedications for chronic comorbidities (e.g., anticoagulants, antiplatelets, statins) or complex conditions (e.g., anticancer agents, immunosuppressants). Newer ARVs such as unboosted integrase inhibitors, doravirine, and fostemsavir have reduced DDI potential, but there are clinically relevant DDIs that warrant consideration. Potential consequences of DDIs include increased toxicity and/or reduced efficacy of ARVs and/or comedications. Management approaches include switching to an ARV with less DDI potential, changing comedications, or altering medication dosage or dosing frequency. Deprescribing strategies can reduce DDIs and polypharmacy, improve adherence, minimize unnecessary adverse effects, and prevent medication-related errors.</p><p><strong>Summary: </strong>Management of DDIs requires close interdisciplinary collaboration from multiple healthcare disciplines (medicine, nursing, pharmacy) across a spectrum of care (community, outpatient, inpatient).</p>","PeriodicalId":10949,"journal":{"name":"Current Opinion in HIV and AIDS","volume":"16 6","pages":"292-302"},"PeriodicalIF":4.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Hepatotoxicity of contemporary antiretroviral drugs. 当代抗逆转录病毒药物的肝毒性。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-11-01 DOI: 10.1097/COH.0000000000000706
Christina G Rivera, Ashley O Otto, John D Zeuli, Zelalem Temesgen

Purpose of review: To date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years.

Recent findings: Although less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents.

Summary: Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.

审查目的:迄今为止,食品和药物管理局已经批准了30多种抗逆转录病毒药物用于治疗艾滋病毒感染。随着具有更好疗效和安全性的新药可用于临床实践,老药要么退出市场,要么不再被积极处方。我们回顾了与当代抗逆转录病毒药物相关的肝毒性,重点是过去3年的数据。最近的发现:尽管最近批准用于治疗HIV的当代抗逆转录病毒药物(即doravirine, ibalizumab, fostemsaver, cabotegravir)的副作用数据较少,但这些药物的严重肝毒性风险似乎很小。摘要:尽管较新的抗逆转录病毒药物比早期的药物耐受性更好,但它们并非完全没有药物不良反应,包括肝毒性。对接受抗逆转录病毒治疗的患者进行紧急肝损伤监测应继续作为常规临床护理的一部分。
{"title":"Hepatotoxicity of contemporary antiretroviral drugs.","authors":"Christina G Rivera,&nbsp;Ashley O Otto,&nbsp;John D Zeuli,&nbsp;Zelalem Temesgen","doi":"10.1097/COH.0000000000000706","DOIUrl":"https://doi.org/10.1097/COH.0000000000000706","url":null,"abstract":"<p><strong>Purpose of review: </strong>To date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years.</p><p><strong>Recent findings: </strong>Although less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents.</p><p><strong>Summary: </strong>Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.</p>","PeriodicalId":10949,"journal":{"name":"Current Opinion in HIV and AIDS","volume":"16 6","pages":"279-285"},"PeriodicalIF":4.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Renal adverse drug reactions. 肾脏药物不良反应。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-11-01 DOI: 10.1097/COH.0000000000000703
Christine Hughes

Purpose of review: Chronic kidney disease (CKD) is common in people living with HIV (PLWH) and is related to a multitude of factors. The aim of this review is to provide an overview of the most recent evidence of renal adverse effects of antiretroviral drugs, predictors of CKD risk and areas for future research.

Recent findings: Advancing age, cardiometabolic risk factors and adverse effects of antiretroviral drugs contribute to the higher prevalence of CKD in PLWH. Genetic factors and baseline clinical CKD risk are strongly correlated to risk of incident CKD, although it is unclear to what extent gene polymorphisms explain renal adverse effects related to tenofovir disoproxil fumarate (TDF). Switching from TDF to tenofovir alafenamide (TAF) in people with baseline renal dysfunction improves renal parameters; however, the long-term safety and benefit of TAF in individuals at low risk of CKD is an area of ongoing research.

Summary: Several factors contribute to estimated glomerular function decline and CKD in PLWH. Clinical risk scores for CKD may be useful to inform selection of ART in an ageing population. In people with baseline renal dysfunction, potentially nephrotoxic antiretroviral drugs should be avoided.

综述目的:慢性肾脏疾病(CKD)在HIV感染者(PLWH)中很常见,与多种因素有关。本综述的目的是概述抗逆转录病毒药物对肾脏不良反应的最新证据,CKD风险的预测因素和未来研究的领域。最近发现:年龄增长、心脏代谢危险因素和抗逆转录病毒药物的不良反应是PLWH患者CKD患病率较高的原因。遗传因素和基线临床CKD风险与发生CKD的风险密切相关,尽管基因多态性在多大程度上解释与富马酸替诺福韦二氧吡酯(TDF)相关的肾脏不良反应尚不清楚。基线肾功能不全患者从TDF切换到替诺福韦阿拉芬胺(TAF)可改善肾脏参数;然而,TAF在低CKD风险个体中的长期安全性和益处是一个正在进行的研究领域。总结:PLWH患者肾小球功能下降和CKD的影响因素有几个。CKD的临床风险评分可能有助于老年人群ART的选择。在基线肾功能不全的人群中,应避免使用具有潜在肾毒性的抗逆转录病毒药物。
{"title":"Renal adverse drug reactions.","authors":"Christine Hughes","doi":"10.1097/COH.0000000000000703","DOIUrl":"https://doi.org/10.1097/COH.0000000000000703","url":null,"abstract":"<p><strong>Purpose of review: </strong>Chronic kidney disease (CKD) is common in people living with HIV (PLWH) and is related to a multitude of factors. The aim of this review is to provide an overview of the most recent evidence of renal adverse effects of antiretroviral drugs, predictors of CKD risk and areas for future research.</p><p><strong>Recent findings: </strong>Advancing age, cardiometabolic risk factors and adverse effects of antiretroviral drugs contribute to the higher prevalence of CKD in PLWH. Genetic factors and baseline clinical CKD risk are strongly correlated to risk of incident CKD, although it is unclear to what extent gene polymorphisms explain renal adverse effects related to tenofovir disoproxil fumarate (TDF). Switching from TDF to tenofovir alafenamide (TAF) in people with baseline renal dysfunction improves renal parameters; however, the long-term safety and benefit of TAF in individuals at low risk of CKD is an area of ongoing research.</p><p><strong>Summary: </strong>Several factors contribute to estimated glomerular function decline and CKD in PLWH. Clinical risk scores for CKD may be useful to inform selection of ART in an ageing population. In people with baseline renal dysfunction, potentially nephrotoxic antiretroviral drugs should be avoided.</p>","PeriodicalId":10949,"journal":{"name":"Current Opinion in HIV and AIDS","volume":"16 6","pages":"303-308"},"PeriodicalIF":4.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
An update on neuropsychiatric adverse effects with second-generation integrase inhibitors and nonnucleoside reverse transcriptase inhibitors. 第二代整合酶抑制剂和非核苷类逆转录酶抑制剂的神经精神不良反应的最新进展。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-11-01 DOI: 10.1097/COH.0000000000000705
Tessa Senneker, Alice Tseng

Purpose of review: Neuropsychiatric adverse effects (NPAE) associated with integrase strand transfer inhibitors (INSTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a growing concern, with higher rates in the real-world compared to phase III trials. This paper reviews the incidence, risk factors, and management of NPAE with second-generation INSTIs, INSTI/rilpivirine dual therapy, and doravirine.

Recent findings: Recent cohort data confirm up to 8% NPAE-associated discontinuations for dolutegravir; NPAE with dolutegravir/rilpivirine therapy are higher than with dolutegravir alone, whereas bictegravir appears similar to dolutegravir. In contrast, NPAE with cabotegravir alone or with rilpivirine appears to be low. Doravirine has NPAE rates similar to rilpivirine and lower than efavirenz. Risk factors for NPAE include female gender, concurrent abacavir use, Sub-Saharan African descent, and age, whereas underlying psychiatric conditions do not appear to increase risk. Strategies to manage NPAE include changing administration time, therapeutic drug monitoring, or regimen modification including within-class INSTI changes. People experiencing NPAE with dolutegravir may tolerate bictegravir.

Summary: Overall, mild to moderate NPAE are associated with INSTIs and newer NNRTIs. Rarely, more severe symptoms may occur and lead to treatment discontinuation. Clinicians should be aware of NPAE to identify and manage drug-related adverse effects.

综述目的:与整合酶链转移抑制剂(intis)和非核苷类逆转录酶抑制剂(NNRTIs)相关的神经精神不良反应(NPAE)越来越受到关注,与III期试验相比,现实世界中的发生率更高。本文综述了第二代INSTI、INSTI/利匹韦林双重治疗和多洛韦林治疗NPAE的发生率、危险因素和管理。最近的研究结果:最近的队列数据证实,高达8%的npae相关停药的dolutegravir;多替重力韦/利匹韦林联合治疗的NPAE高于单独使用多替重力韦,而比替重力韦与多替重力韦相似。相比之下,单用卡波特韦或联用利匹韦林的NPAE似乎较低。多拉韦林的NPAE发生率与利匹韦林相似,低于依非韦伦。NPAE的危险因素包括女性、同时使用阿巴卡韦、撒哈拉以南非洲人后裔和年龄,而潜在的精神疾病似乎不会增加风险。管理NPAE的策略包括改变给药时间、治疗药物监测或方案修改,包括班级内INSTI的改变。服用多替替韦的NPAE患者可以耐受比替替韦。总结:总体而言,轻度至中度NPAE与insi和较新的nnrti相关。在极少数情况下,可能会出现更严重的症状并导致停止治疗。临床医生应了解NPAE,以识别和管理与药物相关的不良反应。
{"title":"An update on neuropsychiatric adverse effects with second-generation integrase inhibitors and nonnucleoside reverse transcriptase inhibitors.","authors":"Tessa Senneker,&nbsp;Alice Tseng","doi":"10.1097/COH.0000000000000705","DOIUrl":"https://doi.org/10.1097/COH.0000000000000705","url":null,"abstract":"<p><strong>Purpose of review: </strong>Neuropsychiatric adverse effects (NPAE) associated with integrase strand transfer inhibitors (INSTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a growing concern, with higher rates in the real-world compared to phase III trials. This paper reviews the incidence, risk factors, and management of NPAE with second-generation INSTIs, INSTI/rilpivirine dual therapy, and doravirine.</p><p><strong>Recent findings: </strong>Recent cohort data confirm up to 8% NPAE-associated discontinuations for dolutegravir; NPAE with dolutegravir/rilpivirine therapy are higher than with dolutegravir alone, whereas bictegravir appears similar to dolutegravir. In contrast, NPAE with cabotegravir alone or with rilpivirine appears to be low. Doravirine has NPAE rates similar to rilpivirine and lower than efavirenz. Risk factors for NPAE include female gender, concurrent abacavir use, Sub-Saharan African descent, and age, whereas underlying psychiatric conditions do not appear to increase risk. Strategies to manage NPAE include changing administration time, therapeutic drug monitoring, or regimen modification including within-class INSTI changes. People experiencing NPAE with dolutegravir may tolerate bictegravir.</p><p><strong>Summary: </strong>Overall, mild to moderate NPAE are associated with INSTIs and newer NNRTIs. Rarely, more severe symptoms may occur and lead to treatment discontinuation. Clinicians should be aware of NPAE to identify and manage drug-related adverse effects.</p>","PeriodicalId":10949,"journal":{"name":"Current Opinion in HIV and AIDS","volume":"16 6","pages":"309-320"},"PeriodicalIF":4.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Editorial: Immune-mediated control of HIV. 编辑:免疫介导的HIV控制。
IF 4.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-09-01 DOI: 10.1097/COH.0000000000000698
Katharine J Bar, Ole S Søgaard
{"title":"Editorial: Immune-mediated control of HIV.","authors":"Katharine J Bar,&nbsp;Ole S Søgaard","doi":"10.1097/COH.0000000000000698","DOIUrl":"https://doi.org/10.1097/COH.0000000000000698","url":null,"abstract":"","PeriodicalId":10949,"journal":{"name":"Current Opinion in HIV and AIDS","volume":"16 5","pages":"241-242"},"PeriodicalIF":4.1,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Current Opinion in HIV and AIDS
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