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Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV. 关于抗逆转录病毒疗法对艾滋病毒感染者体重增加和肥胖所起作用的最新数据。
IF 4.1 3区 医学 Q1 Nursing Pub Date : 2023-11-06 DOI: 10.1097/coh.0000000000000833
Jacqueline Capeau, Claire Lagathu, Véronique Béréziat
Antiretroviral therapy (ART) has long been implicated in fat alterations and weight variations leading to cardiometabolic consequences. Recent largely prescribed antiretrovirals (ARVs) from the integrase-strand-transfer-inhibitor (INSTI) class have been associated with excessive weight gain/obesity in a minority of persons with HIV (PWH). As well, in the nucleoside reverse transcriptase inhibitors (NRTI) class, tenofovir-alafenamide (TAF), often replacing tenofovir-disoproxil-fumarate (TDF), has been associated with weight gain, a worrying concern in the present worldwide obesogenic environment. The respective role of the different ARV, the risk factors and the mechanisms remain questionable.
长期以来,抗逆转录病毒疗法(ART)一直被认为与导致心脏代谢后果的脂肪改变和体重变化有关。在少数艾滋病病毒感染者(PWH)中,近期主要处方的整合酶-链转移抑制剂(INSTI)类抗逆转录病毒药物(ARV)与体重过度增加/肥胖有关。此外,在核苷类逆转录酶抑制剂(NRTI)中,替诺福韦-阿拉非那胺(TAF)经常取代替诺福韦-二异丙嗪-富马酸盐(TDF),也与体重增加有关,这在目前全球肥胖的大环境下令人担忧。不同抗逆转录病毒药物各自的作用、风险因素和机制仍存在疑问。
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引用次数: 0
Discovery medicine - the HVTN's iterative approach to developing an HIV-1 broadly neutralizing vaccine. 探索医学-HVTN开发HIV-1广泛中和疫苗的迭代方法。
IF 4.5 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-11-01 Epub Date: 2023-09-13 DOI: 10.1097/COH.0000000000000821
Troy M Martin, Sam T Robinson, Yunda Huang

Purpose of review: In the past two decades, there has been an explosion in the discovery of HIV-1 broadly neutralizing antibodies (bnAbs) and associated vaccine strategies to induce them. This abundance of approaches necessitates a system that accurately and expeditiously identifies the most promising regimens. We herein briefly review the background science of bnAbs, provide a description of the first round of phase 1 discovery medicine studies, and suggest an approach to integrate these into a comprehensive HIV-1-neutralizing vaccine.

Recent findings: With recent preclinical success including induction of early stage bnAbs in mouse knockin models and rhesus macaques, successful priming of VRC01-class bnAbs with eOD-GT8 in a recent study in humans, and proof-of-concept that intravenous infusion of VRC01 prevents sexual transmission of virus in humans, the stage is set for a broad and comprehensive bnAb vaccine program. Leveraging significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, the HVTN has reconfigured its HIV-1 vaccine strategy by developing the Discovery Medicine Program to test promising vaccine candidates targeting six key epitopes.

Summary: The HVTN Discovery Medicine program is testing multiple HIV-1-neutralizing vaccine candidates.

综述目的:在过去的二十年里,HIV-1广泛中和抗体(bnAbs)和诱导它们的相关疫苗策略的发现激增。这种丰富的方法需要一个准确、快速地确定最有前景的治疗方案的系统。我们在此简要回顾了bnAbs的背景科学,提供了第一轮1期发现医学研究的描述,并提出了一种将这些研究整合到全面的HIV-1中和疫苗中的方法。最近的发现:随着最近的临床前成功,包括在小鼠敲除模型和恒河猴中诱导早期bnAbs,在最近的一项人类研究中用eOD-GT8成功启动VRC01类bnAbs以及静脉输注VRC01防止病毒在人类中性传播的概念证明,为广泛而全面的bnAb疫苗计划奠定了基础。利用蛋白质纳米颗粒科学、信使核糖核酸技术、佐剂开发以及B细胞和抗体分析方面的重大进展,HVTN通过开发发现医学计划来重新配置其HIV-1疫苗策略,以测试针对六个关键表位的有前景的候选疫苗。综述:HVTN发现医学项目正在测试多种HIV-1中和候选疫苗。
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引用次数: 0
Guiding HIV-1 vaccine development with preclinical nonhuman primate research. 指导临床前非人灵长类动物研究的HIV-1疫苗开发。
IF 4.5 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-11-01 Epub Date: 2023-09-11 DOI: 10.1097/COH.0000000000000819
James A Counts, Kevin O Saunders

Purpose of the review: Nonhuman primates (NHPs) are seen as the closest animal model to humans in terms of anatomy and immune system makeup. Here, we review how preclinical studies in this model system are teaching the field of HIV vaccinology the basic immunology that is needed to induce broadly neutralizing antibodies (bnAbs) with vaccination and elicit protective T cell responses. These lessons are being translated into clinical trials to advance towards protective active vaccination against HIV-1 infection.

Recent findings: Preclinical vaccination studies in NHPs have shown that highly engineered HIV-1 immunogens can initiate bnAb precursors providing proof of concept for Phase I clinical trials. Additionally, NHP models of HIV-1 infection are elucidating the pathways for bnAb development while serving as systems to evaluate vaccine protection. Innovative immunization strategies have increased affinity maturation of HIV-1 antibodies in long-lived germinal centers. Preclinical studies in macaques have defined the protective level of neutralizing antibodies and have shown that T cell responses can synergize with antibody-mediated immunity to provide protection in the presence of lower neutralizing antibody titers.

Summary: The NHP model provides vaccine regimens and desired antibody and T cell responses that serve as benchmarks for clinical trials, accelerating HIV vaccine design.

综述的目的:在解剖学和免疫系统组成方面,非人类灵长类动物(NHP)被视为最接近人类的动物模型。在这里,我们回顾了该模型系统中的临床前研究如何教授HIV疫苗学领域通过疫苗接种诱导广泛中和抗体(bnAbs)并引发保护性T细胞反应所需的基本免疫学。这些经验教训正在转化为临床试验,以推进针对HIV-1感染的保护性主动疫苗接种。最近的发现:NHP的临床前疫苗接种研究表明,高度工程化的HIV-1免疫原可以启动bnAb前体,为I期临床试验提供了概念证明。此外,HIV-1感染的NHP模型正在阐明bnAb发展的途径,同时作为评估疫苗保护性的系统。创新的免疫策略提高了HIV-1抗体在长寿生发中心的亲和力成熟度。猕猴的临床前研究已经确定了中和抗体的保护水平,并表明T细胞反应可以与抗体介导的免疫协同作用,在中和抗体滴度较低的情况下提供保护。总结:NHP模型提供了疫苗方案以及所需的抗体和T细胞反应,作为临床试验的基准,加速了HIV疫苗的设计。
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引用次数: 0
'Immunization during ART and ATI for HIV-1 vaccine discovery/development'. “用于HIV-1疫苗发现/开发的ART和ATI期间的免疫”。
IF 4.1 3区 医学 Q1 Nursing Pub Date : 2023-11-01 Epub Date: 2023-09-08 DOI: 10.1097/COH.0000000000000817
Leonidas Stamatatos

Purpose of review: Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that promote and guide the full maturation of broadly neutralizing antibody responses.

Recent findings: The HIV-1 envelope glycoprotein (Env) does not efficiently engage the germline precursors of broadly neutralizing antibodies (bnAbs). However, Env-derived proteins specifically designed to precisely do that, have been recently developed. These 'germline-targeting' Env immunogens activate naïve B cells that express the germline precursors of bnAbs but by themselves cannot guide their maturation towards their broadly neutralizing forms. This requires sequential immunizations with heterologous sets of Envs. These 'booster' Envs are currently unknown.

Summary: Combining germline-targeting Env immunization approaches during ART with ATI could lead to the identification of natural Envs that are responsible for the maturation of broadly neutralizing antibody responses during infection. Such Envs could then serve as booster immunogens to guide the maturation of glBCRs that have become activated by germline-targeting immunogens in uninfected subjects.

综述目的:探讨在ART期间用种系靶向Env免疫原进行免疫接种,然后进行ATI,是否能鉴定出促进和引导广泛中和抗体反应完全成熟的病毒包膜糖蛋白(Envs)。最近的发现:HIV-1包膜糖蛋白(Env)不能有效地与广泛中和抗体(bnAbs)的种系前体结合。然而,最近已经开发出了专门为实现这一目的而设计的Env衍生蛋白质。这些“种系靶向”Env免疫原激活了表达bnAbs种系前体的幼稚B细胞,但其自身无法引导其成熟为广泛的中和形式。这需要用异源Env进行连续免疫。这些“助推器”环境目前未知。总结:在ART期间将种系靶向Env免疫方法与ATI相结合,可以鉴定出在感染期间负责广泛中和抗体反应成熟的天然Env。这样的Env可以作为加强免疫原来指导glBCR的成熟,这些glBCR已被未感染受试者的种系靶向免疫原激活。
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引用次数: 1
The changing use and program costs of HIV-related laboratory testing over 20 years in an HIV cohort. 20年来艾滋病毒队列中艾滋病毒相关实验室检测的使用变化和项目成本
IF 4.1 3区 医学 Q1 Nursing Pub Date : 2023-09-01 DOI: 10.1097/COH.0000000000000814
Jessica Dalere, Raynell Lang, Hartmut B Krentz, Brenda Beckthold, M John Gill

Purpose of review: The improved health of persons with HIV (PWH) resulting from antiretroviral therapy (ART) has led to recommendations for reduced laboratory monitoring. We studied, for all PWH in care over 20 years at the Southern Alberta Clinic (SAC), Canada, the changing use and results of HIV-specific laboratory testing [i.e., CD4+ testing, plasma HIV viral load (PVL), and genotypic antiretroviral resistance testing (GART)].In this descriptive retrospective longitudinal cohort observational study, we examined HIV-specific laboratory testing for all PWH from 2000 to 2020 within the context of HIV-related health outcomes, program costs, and mortality.

Recent findings: The number of PWH in care increased from 755 in 2000 to 2050 in 2020. Annual CD4+ testing per PWH increased from 2.7 per person in 2000 peaking to 3.5 in 2005 but decreasing to 1.4 by 2020. Annual PVL tests per PWH gradually decreased from 3.2 in 2000 to 2.0 in 2020. GART increased from 93 tests in 2000 to 315 in 2008 decreasing to 127 in 2020. Patients received GART at baseline, and after a viral breakthrough when indicated. Viral suppression rates for the population increased from 66 to 96%; median CD4+ cell count increased from 443 to 470 cells/μl, and overall morbidity decreased from 9.2 to 2.0% by 2020, respectively. Annual per patient laboratory costs decreased from a high of $302 in 2008 to $161 by 2020.

Summary: The reduced annual laboratory surveillance per PWH associated with modern ART resulted in modest cost savings and no apparent loss in quality of HIV care.

审查目的:抗逆转录病毒治疗(ART)改善了艾滋病毒感染者(PWH)的健康状况,因此建议减少实验室监测。我们研究了在加拿大南阿尔伯塔诊所(SAC)治疗20多年的所有PWH患者中,HIV特异性实验室检测(即CD4+检测、血浆HIV病毒载量(PVL)和基因型抗逆转录病毒耐药性检测(GART))的使用变化和结果。在这项描述性回顾性纵向队列观察研究中,我们在与hiv相关的健康结果、项目成本和死亡率的背景下,检查了2000年至2020年所有PWH的hiv特异性实验室检测。最新发现:护理中的PWH人数从2000年的755人增加到2020年的2050人。每个PWH每年的CD4+检测从2000年的每人2.7次增加到2005年的3.5次,但到2020年下降到1.4次。每艘PWH每年的PVL测试从2000年的3.2次逐渐下降到2020年的2.0次。GART测试从2000年的93次增加到2008年的315次,减少到2020年的127次。患者在基线时接受GART治疗,并在病毒突破后接受治疗。种群的病毒抑制率从66%提高到96%;到2020年,中位CD4+细胞计数从443个增加到470个/μl,总发病率从9.2%下降到2.0%。每位患者每年的实验室费用从2008年的302美元降至2020年的161美元。摘要:与现代抗逆转录病毒治疗相关的每个PWH的年度实验室监测减少导致了适度的成本节约,并且没有明显的艾滋病毒护理质量损失。
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引用次数: 0
Decrypting biological hallmarks of aging in people with HIV. 破解艾滋病毒感染者衰老的生物学特征。
IF 4.1 3区 医学 Q1 Nursing Pub Date : 2023-09-01 DOI: 10.1097/COH.0000000000000810
Thomas A Premeaux, Lishomwa C Ndhlovu

Purpose of review: HIV infection adds further complexity to the heterogenous process of aging. In this focused review, we examine and discuss recent advances to better elucidate mechanisms of biological aging perturbed and accelerated in the context of HIV, particularly among those with viral suppression through the benefits of antiretroviral therapy (ART). New hypotheses from these studies are poised to provide an improved understanding of multifaceted pathways that converge and likely form the basis for effective interventions toward successful aging.

Recent findings: Evidence to date suggests multiple mechanisms of biological aging impact people living with HIV (PLWH). Recent literature delves and expands on how epigenetic alterations, telomere attrition, mitochondrial perturbations, and intercellular communications may underpin accelerated or accentuated aging phenotypes and the disproportionate prevalence of age-related complications among PLWH. Although most hallmarks of aging are likely exacerbated in the setting of HIV, ongoing research efforts are providing new insight on the collective impact these conserved pathways may have in the aging disease processes.

Summary: New knowledge on underlying molecular disease mechanisms impacting people aging with HIV are reviewed. Also examined are studies that may facilitate the development and implementation of effective therapeutics and guidance on improving geriatric HIV clinical care.

综述目的:HIV感染使衰老的异质性过程更加复杂。在这篇重点综述中,我们检查和讨论了最近的进展,以更好地阐明在艾滋病毒背景下生物衰老的紊乱和加速机制,特别是在那些通过抗逆转录病毒治疗(ART)抑制病毒的患者中。来自这些研究的新假设准备提供对多方面途径的更好理解,这些途径汇聚在一起,可能形成有效干预成功衰老的基础。最新发现:迄今为止的证据表明,生物衰老影响艾滋病毒感染者(PLWH)的多种机制。最近的文献深入并扩展了表观遗传改变,端粒磨损,线粒体扰动和细胞间通讯如何支持加速或加剧衰老表型以及PLWH中年龄相关并发症的不成比例流行。尽管大多数衰老标志可能在HIV环境下加剧,但正在进行的研究工作正在为这些保守途径在衰老疾病过程中可能产生的集体影响提供新的见解。综述了影响HIV感染者衰老的潜在分子疾病机制的新知识。还审查了可能促进制定和实施有效治疗方法的研究,以及改善老年艾滋病毒临床护理的指导。
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引用次数: 0
HIV-1 transcriptional modulation: novel host factors and prospective therapeutic strategies. HIV-1 转录调节:新型宿主因素和前瞻性治疗策略。
IF 4.5 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-09-01 Epub Date: 2023-07-17 DOI: 10.1097/COH.0000000000000808
Quentin M R Gibaut, Luisa P Mori, Susana T Valente

Purpose of review: This review highlights advances in HIV transcription and epigenetic latency mechanisms and outlines current therapeutic approaches to eliminate or block the HIV-1 latent reservoir.

Recent findings: Novel host factors have been reported to modulate HIV-1 transcription and latency. Chromatin affinity purification strategies followed by mass spectrometry (ChAP-MS) identified the chaperone protein p32 to play an important role in HIV-1 transcriptional regulation via interactions with the viral transcriptional activator Tat. Similarly, an shRNA screen identified the methyltransferase SMYD5 contributing to HIV-1 transcriptional activation also by modulating Tat activity. These new factors, among others, represent potential druggable targets that could be explored in the 'block-and-lock' or 'shock-and-kill' approaches.

Summary: The HIV-1 latent reservoir is established early after infection, persists during antiretroviral therapy, and is the source of viral rebound after treatment interruption. An HIV cure requires either eliminating this reservoir or blocking latent proviral reactivation in the absence of antiretroviral therapy (ART). Understanding the mechanisms and key-players modulating HIV transcriptional and reactivation may facilitate therapeutic advancements. Here we summarize, the latest findings on host factors' roles in HIV transcriptional regulation.

综述的目的:本综述重点介绍了 HIV 转录和表观遗传潜伏机制方面的进展,并概述了目前消除或阻断 HIV-1 潜伏库的治疗方法:据报道,新的宿主因子可以调节 HIV-1 的转录和潜伏。染色质亲和纯化策略和质谱分析(ChAP-MS)发现,伴侣蛋白 p32 通过与病毒转录激活因子 Tat 相互作用,在 HIV-1 转录调控中发挥着重要作用。同样,通过 shRNA 筛选发现,甲基转移酶 SMYD5 也通过调节 Tat 的活性来促进 HIV-1 的转录激活。摘要:HIV-1 潜伏库在感染后早期建立,在抗逆转录病毒治疗期间持续存在,是治疗中断后病毒反弹的源头。要治愈艾滋病毒,就必须在没有抗逆转录病毒疗法(ART)的情况下消除潜伏库或阻断潜伏前病毒的再激活。了解调节艾滋病病毒转录和再激活的机制和关键角色可能会促进治疗的进步。在此,我们总结了有关宿主因子在 HIV 转录调控中作用的最新发现。
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引用次数: 0
Editorial introductions. 编辑介绍。
IF 4.1 3区 医学 Q1 Nursing Pub Date : 2023-09-01 DOI: 10.1097/COH.0000000000000811
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引用次数: 0
Features of functional and dysfunctional CD8+ T cells to guide HIV vaccine development. 功能性和失调性 CD8+ T 细胞的特征,以指导 HIV 疫苗的开发。
IF 4.5 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-09-01 Epub Date: 2023-07-18 DOI: 10.1097/COH.0000000000000812
Shaown Bhattacharyya, Charles R Crain, Benjamin Goldberg, Gaurav D Gaiha

Purpose of review: CD8+ T cell responses are a key component of the host immune response to human immunodeficiency virus (HIV) but vary significantly across individuals with distinct clinical outcomes. These differences help inform the qualitative features of HIV-specific CD8+ T cells that we should aim to induce by vaccination.

Recent findings: We review previous and more recent findings on the features of dysfunctional and functional CD8+ T cell responses that develop in individuals with uncontrolled and controlled HIV infection, with particular emphasis on proliferation, cytotoxic effector function, epitope specificity, and responses in lymph nodes. We also discuss the implications of these findings for both prophylactic and therapeutic T cell vaccine development within the context of T cell vaccine trials.

Summary: The induction of HIV specific CD8+ T cell responses is an important goal of ongoing vaccine efforts. Emerging data on the key features of CD8+ T cell responses that distinguish individuals who spontaneously control from those with progressive disease continues to provide key guidance.

综述的目的:CD8+ T细胞反应是宿主对人类免疫缺陷病毒(HIV)免疫反应的关键组成部分,但不同个体的临床结果差异很大。这些差异有助于我们了解通过接种疫苗诱导的 HIV 特异性 CD8+ T 细胞的质量特征:我们回顾了以前和最近关于未控制和已控制 HIV 感染者体内功能失调和功能性 CD8+ T 细胞反应特征的研究结果,特别强调了增殖、细胞毒性效应器功能、表位特异性和淋巴结中的反应。我们还在 T 细胞疫苗试验的背景下讨论了这些发现对预防性和治疗性 T 细胞疫苗开发的影响。摘要:诱导 HIV 特异性 CD8+ T 细胞应答是当前疫苗工作的一个重要目标。有关 CD8+ T 细胞应答的关键特征的新数据将继续为区分自发控制和疾病进展的个体提供重要指导。
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引用次数: 0
Impact of early antiretroviral therapy, early life immunity and immune sex differences on HIV disease and posttreatment control in children. 早期抗逆转录病毒治疗、早期生命免疫和免疫性别差异对儿童艾滋病和治疗后控制的影响。
IF 4.1 3区 医学 Q1 Nursing Pub Date : 2023-09-01 Epub Date: 2023-07-06 DOI: 10.1097/COH.0000000000000807
Nicholas G Herbert, Philip J R Goulder

Purpose of review: To review recent insights into the factors affecting HIV disease progression in children living with HIV, contrasting outcomes: following early ART initiation with those in natural, antiretroviral therapy (ART)-naive infection; in children versus adults; and in female individuals versus male individuals.

Recent findings: Early life immune polarization and several factors associated with mother-to-child transmission of HIV result in an ineffective HIV-specific CD8+ T-cell response and rapid disease progression in most children living with HIV. However, the same factors result in low immune activation and antiviral efficacy mediated mainly through natural killer cell responses in children and are central features of posttreatment control. By contrast, rapid activation of the immune system and generation of a broad HIV-specific CD8+ T-cell response in adults, especially in the context of 'protective' HLA class I molecules, are associated with superior disease outcomes in ART-naive infection but not with posttreatment control. The higher levels of immune activation in female individuals versus male individuals from intrauterine life onwards increase HIV infection susceptibility in females in utero and may favour ART-naive disease outcomes rather than posttreatment control.

Summary: Early-life immunity and factors associated with mother-to-child transmission typically result in rapid HIV disease progression in ART-naive infection but favour posttreatment control in children following early ART initiation.

综述的目的:回顾影响艾滋病毒感染儿童艾滋病毒疾病进展的因素的最新见解,对比结果:早期开始抗逆转录病毒疗法(ART)后与自然抗逆转录病毒治疗(ART)早期感染的结果;儿童与成人;以及女性个体与男性个体。最近的发现:在大多数艾滋病毒感染儿童中,早期免疫极化和与艾滋病毒母婴传播相关的几个因素导致了无效的艾滋病毒特异性CD8+T细胞反应和快速的疾病进展。然而,同样的因素导致儿童主要通过自然杀伤细胞反应介导的免疫激活和抗病毒效果低下,这是治疗后控制的核心特征。相比之下,在成人中,免疫系统的快速激活和广泛的HIV特异性CD8+T细胞反应的产生,特别是在“保护性”HLA I类分子的情况下,与ART初始感染的优越疾病结果有关,但与治疗后控制无关。从子宫内开始,女性个体的免疫激活水平高于男性个体,这增加了女性在子宫内感染艾滋病毒的易感性,并可能有利于ART早期疾病的结果,而不是治疗后的控制。综述:早期生命免疫和与母婴传播相关的因素通常会导致早期ART感染的HIV疾病快速进展,但有利于早期开始ART后儿童的治疗后控制。
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引用次数: 0
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Current Opinion in HIV and AIDS
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