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Fixation and reversion of mutations in the receptor-binding domain of the SARS-CoV-2 spike protein: A 2020-2024 analysis.
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-30 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100581
Daniele Focosi, Pietro Giorgio Spezia, Fabrizio Maggi
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引用次数: 0
Bypassing primary antiretroviral therapy centres in Sub-Saharan Africa: An integrative review of the theoretical and empirical literature.
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-27 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100580
Maximillian Kolbe Domapielle, Sadat Zakari Abugbila, Marshall Kala

The uptake of antiretroviral therapy (ART) is critical to meeting the global HIV treatment goal of 95-95-95 by 2025. Although a few Sub-Saharan African countries have already achieved this target, the prevalence of bypassing primary ART centres in many countries in the subregion has negative implications for ART uptake and use. This study used the access to health services framework to analyse the evidence and factors contributing to bypassing primary ART centres by individuals in the sub-region seeking HIV care and support. We found compelling evidence of the prevalence of ART clients bypassing their primary ART centres in search of specialised care in higher-tiered health facilities. Others use bypassing to conceal their HIV-positive status to avoid social stigma. We argue that introducing specialised and differentiated ART at the primary level of care can address this phenomenon. While we anticipate that this measure will satisfy clients' desire for specialised care, we recommend enhancing public awareness about the effectiveness of ART to reduce stigma towards ART clients. Legislation and strict enforcement of anti-HIV stigma laws, which outlaw and criminalise stigmatising people living with HIV (PLHIV), could potentially be an effective stigma-deterring measure. To complement this effort, PLHIV should be empowered to understand legislative instruments and steps to take when confidentiality and discriminatory issues arise. We recommend further research in Sub-Saharan Africa to investigate the relationship between bypassing primary ART centres and client adherence. The findings will help design appropriate strategies to increase ART uptake at primary ART centres.

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引用次数: 0
Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal. HIV-1亚型C潜伏期模型的建立及长末端重复元件遗传变异对潜伏期逆转的影响
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-13 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100575
Shreyal Maikoo, Robert-Jan Palstra, Krista L Dong, Tokameh Mahmoudi, Thumbi Ndung'u, Paradise Madlala

Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus. Furthermore, the impact of genetic variation between viral subtypes, specifically within the long terminal repeat (LTR) element of the viral transcriptional promoter on latency reversal, remains unclear. To address this scientific gap, we constructed a minimal genome retroviral vector expressing HIV-1C consensus transactivator of transcription protein (Tat) and green fluorescent protein (GFP) under the control of either HIV-1C consensus LTR (C731CC) or the transmitted/founder (T/F) LTRs derived from PLWH (CT/F731CC), produced corresponding LTR pseudotyped viruses using a vesicular stomatitis virus (VSV-G) pseudotyped Envelope vector and the pCMVΔR8.91 packaging vector containing HIV-1 accessory and rev genes. Viruses produced in this way were used to infect Jurkat E6 and primary CD4+ T cells in vitro. By enriching for latently infected cells, and treating them with different latency reversing agents, we developed an HIV-1C latency model that demonstrated that the HIV-1C consensus LTR has lower reactivation potential compared to its HIV-1B counterpart. Furthermore, HIV-1C T/F LTR pseudotyped proviral genetic variants exhibited a heterogenous reactivation response which was modulated by host cell (genetic) variation. Our data suggests that genetic variation both within and between HIV-1 subtypes influences latency reversal. Future studies should investigate the specific role of variation in host cellular environment on reactivation differences.

撒哈拉以南非洲占全球艾滋病毒感染者(PLWH)的近 70%,其中南非的感染者人数最多,98%的感染是由 C 亚型(HIV-1C)引起的。然而,流行于欧洲和北美的 HIV-1 B 亚型(HIV-1B)尽管只占全球 HIV-1 感染者的 12%,却一直是大多数治愈研究和测试的重点。开发非 B 亚型病毒的潜伏模型是解决这一过度关注问题的必要步骤。此外,病毒亚型之间的基因变异,特别是病毒转录启动子长末端重复(LTR)元件内的基因变异对潜伏逆转的影响仍不清楚。为了弥补这一科学空白,我们构建了一种最小基因组逆转录病毒载体,在 HIV-1C 共识 LTR(C731CC)或来自 PLWH 的传输/创始(T/F)LTR(CT/F731CC)的控制下表达 HIV-1C 共识转录激活蛋白(Tat)和绿色荧光蛋白(GFP)、使用水泡性口炎病毒(VSV-G)伪型包膜载体和 pCMVΔR8.91 包装载体,其中含有 HIV-1 辅助基因和 rev 基因。用这种方法产生的病毒在体外感染 Jurkat E6 细胞和原代 CD4+ T 细胞。通过富集潜伏感染的细胞并用不同的潜伏逆转剂处理这些细胞,我们建立了一个 HIV-1C 潜伏模型,该模型证明 HIV-1C 共识 LTR 与 HIV-1B 对应基因相比具有更低的再激活潜能。此外,HIV-1C T/F LTR 伪型前病毒基因变体表现出异质性的再激活反应,这种反应受宿主细胞(基因)变异的调节。我们的数据表明,HIV-1 亚型内部和之间的基因变异都会影响潜伏期的逆转。未来的研究应探讨宿主细胞环境变异对再激活差异的具体作用。
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引用次数: 0
Assessing favipiravir impact on SARS-CoV-2 transmission within households: Insights from a multi-center study (FaviPrev). 评估favipiravir对家庭内SARS-CoV-2传播的影响:来自多中心研究的见解(FaviPrev)。
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-12 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100576
Taweegrit Siripongboonsitti, Marisa Muadchimkaew, Kriangkrai Tawinprai, Ornisa Issaranon, Wichuda Meepholkij, Pureepat Arttawejkul, Apiradee Vararungzarit, Onwalee Dhissayakamol, Wilaiporn Preeyachit, Kamonwan Soonklang, Nithi Mahanonda

Background: While certain studies have demonstrated that antiviral treatment administered to index patients with influenza can mitigate the transmission within households, the efficacy of anti-SARS-CoV-2 agents in curtailing household transmission remains to be conclusively established.

Methods: A retrospective study conducted from April 2021 to May 2022 across multiple centers in Thailand compared 892 individuals treated with favipiravir to 84 who received standard treatment among mild to moderate COVID-19 index patients. The study focused on the impact of favipiravir treatment in reducing household SARS-CoV-2 transmission by examining the secondary attack rate.

Results: Favipiravir significantly reduced household SARS-CoV-2 transmission, comparing 1836 household contacts with favipiravir-treated index cases to 170 contacts whose index cases received standard care. Favipiravir led to a 58 % secondary attack rate, substantially lower than the 71.8 % observed with standard treatment, representing a 54 % reduction in transmission likelihood, with an odds ratio of 0.46 (95 % confidence interval [CI] [0.23-0.89]). Index cases treated with favipiravir also demonstrated a relative risk reduction of 0.19 in transmission (95 % CI [0.11-0.27]). Remarkably, favipiravir effectiveness was most notable in unvaccinated index cases, those with symptomatic infections, individuals living in shared spaces like dormitories, flats, or apartments, and those not adhering to mask-wearing within their households.

Conclusions: Favipiravir has demonstrated in this study an indirect role in reducing household SARS-CoV-2 transmission, showing notable efficacy in symptomatic and unvaccinated index cases. This breakthrough highlights its potential in broader public health strategies. Exploring the roles and challenges of other anti-SARS-CoV-2 agents remains a vital goal in ongoing research.

背景:虽然某些研究表明,对流感患者进行抗病毒治疗可以减轻家庭内的传播,但抗sars - cov -2药物在减少家庭传播方面的功效仍有待最终确定。方法:2021年4月至2022年5月,在泰国多个中心进行了一项回顾性研究,比较了在轻至中度COVID-19指数患者中接受favipiravir治疗的892名患者和接受标准治疗的84名患者。该研究通过检查继发率,重点研究了favipiravir治疗对减少家庭SARS-CoV-2传播的影响。结果:Favipiravir显著降低了家庭SARS-CoV-2传播,比较了1836例favipirvir治疗的家庭接触者和170例接受标准治疗的家庭接触者。Favipiravir导致58%的二次发作率,大大低于标准治疗的71.8%,代表传播可能性降低54%,优势比为0.46(95%可信区间[CI][0.23-0.89])。favipiravir治疗的指数病例也显示传播的相对风险降低了0.19 (95% CI[0.11-0.27])。值得注意的是,favipiravir的有效性在未接种疫苗的指数病例、有症状的感染者、住在宿舍、公寓或公寓等共用空间的个人以及在家中不坚持戴口罩的人身上最为显著。结论:在本研究中,Favipiravir在减少家庭SARS-CoV-2传播方面具有间接作用,在有症状和未接种疫苗的指数病例中表现出显著疗效。这一突破突出了其在更广泛的公共卫生战略中的潜力。探索其他抗sars - cov -2药物的作用和挑战仍然是正在进行的研究的重要目标。
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引用次数: 0
Hepatitis B prevalence in an endemic area of hepatitis C virus: A population-based study implicated in hepatitis elimination in Thailand. 乙型肝炎流行在丙型肝炎病毒流行地区:一项基于人群的研究涉及在泰国消除肝炎。
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-11 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100577
Nawarat Posuwan, Rujipat Wasitthankasem, Napaporn Pimsing, Wijittra Phaengkha, Saranya Ngamnimit, Preeyaporn Vichaiwattana, Sirapa Klinfueng, Maneerat Raksayod, Yong Poovorawan

Chronic hepatitis B (HBV) and C (HCV) are major health challenges in Thailand, with Phetchabun province, a known HCV-endemic area, being a key target for elimination efforts. This study aimed to assess HBV prevalence and identify associated risk factors in this province. Data was collected from three cross-sectional population studies: (1) adults in 2015 (n = 1,667, age 30-64 years), (2) young adults in 2017 (n = 1,453, age 18-30 years), both from high HCV-endemic districts, and (3) a province-wide study in 2018 (n = 4,769, age 35-64 years). Plasma samples were tested for HBsAg using the ARCHITECT assay. Results showed HBsAg seropositivity in 3.1 % of young adults in high-endemic districts, with significant associations with age, education, injecting drug use, and MSM behavior. Among adults, HBsAg prevalence was 5.9 %, linked to age and family liver disease history. Province-wide, 6.3 % of adults tested positive, with factors like gender and history of blood donation playing significant roles. Notably, age and blood donation were protective factors against HBV in adults. Analysis revealed a moderate HBV prevalence in those born before Thailand Expanded Program on Immunization (EPI) program, while those born after had rates below 1 %. The findings emphasize distinct HBV transmission patterns in different age groups, influenced by social and behavioral shifts. This knowledge is crucial for effective hepatitis elimination strategies in the Phetchabun province and nationwide.

慢性乙型肝炎(HBV)和丙型肝炎(HCV)是泰国面临的主要卫生挑战,众所周知的HCV流行区Phetchabun省是消除工作的关键目标。本研究旨在评估该省份的HBV患病率并确定相关危险因素。数据收集自三个横断面人群研究:(1)2015年的成年人(n = 1667,年龄30-64岁),(2)2017年的年轻人(n = 1453,年龄18-30岁),均来自hcv高流行区,(3)2018年的全省研究(n = 4769,年龄35-64岁)。血浆样品采用ARCHITECT法检测HBsAg。结果显示,在高流行区,3.1%的年轻人HBsAg血清阳性,与年龄、教育程度、注射吸毒和MSM行为显著相关。在成人中,HBsAg患病率为5.9%,与年龄和家族肝病史有关。全省范围内,6.3%的成年人检测呈阳性,性别和献血史等因素起着重要作用。值得注意的是,年龄和献血是成人抗HBV的保护因素。分析显示,在泰国扩大免疫规划(EPI)规划之前出生的人群中,HBV的患病率为中等水平,而在EPI规划之后出生的人群中,HBV的患病率低于1%。研究结果强调,受社会和行为转变的影响,不同年龄组的HBV传播模式不同。这一知识对于在Phetchabun省和全国范围内有效消除肝炎战略至关重要。
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引用次数: 0
Relatively high interest but limited active engagement in HIV cure research: Awareness, interest, and information-seeking among affected communities in the Netherlands. 对艾滋病毒治疗研究的兴趣相对较高,但积极参与有限:荷兰受影响社区的认识、兴趣和信息寻求。
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-09 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100570
Maaike A J Noorman, John B F de Wit, Tamika A Marcos, Sarah E Stutterheim, Thijs Albers, Kai J Jonas, Chantal den Daas

Background: Community engagement is important for inclusive HIV cure development. This study evaluates current engagement in HIV cure research among affected communities in the Netherlands by analyzing awareness, interest, and information-seeking behavior. It also identifies participant characteristics and HIV-related illness perceptions linked to each engagement stage.

Methods: A cross-sectional survey was conducted from July 2023 to March 2024, involving 499 people with HIV and 578 individuals without HIV, including partners and gay, bisexual, and other men who have sex with men. Multivariate regression analyses examined the relationships between participant characteristics, HIV-related illness perceptions, and three outcomes: awareness, interest, and information-seeking.

Results: The mean awareness was 3.08 (SD = 0.99) interest was higher at 3.67 (SD = 0.85), while the information-seeking frequency was lower at 2.33 (SD = 0.97). Higher awareness was seen in older participants, non-cisgender men, and those with increased perceived control and comprehensibility of HIV. Interest in cure research was higher among people with HIV, those with a migration background, individuals with steady partner(s), and those experiencing greater HIV-related concerns, negative HIV-related emotions, and better HIV comprehension. Information-seeking frequency was greater among people with HIV, those with a bachelor's degree, individuals from a migration background, those with steady partner(s), and those perceiving more severe HIV-related symptoms, and heightened concerns and negative emotions about HIV.

Conclusion: While moderate awareness exists, engagement remains passive with limited information-seeking; however, significant interest in a cure underscores the need for enhanced communication efforts to foster inclusive HIV cure development.

背景:社区参与对包容性艾滋病毒治疗发展非常重要。本研究通过分析意识、兴趣和信息寻求行为,评估了荷兰受影响社区目前参与艾滋病治疗研究的情况。它还确定了参与者的特征和与每个参与阶段相关的艾滋病毒相关疾病的看法。方法:于2023年7月至2024年3月对499名HIV感染者和578名未感染HIV的人进行横断面调查,包括伴侣和同性恋、双性恋和其他男男性行为者。多变量回归分析检验了参与者特征、艾滋病相关疾病认知和三个结果之间的关系:意识、兴趣和信息寻求。结果:平均知晓率为3.08 (SD = 0.99),兴趣度较高,为3.67 (SD = 0.85),信息寻求频率较低,为2.33 (SD = 0.97)。年龄较大的参与者、非顺性男性以及对艾滋病毒的控制和理解程度较高的参与者意识较高。对治疗研究的兴趣在艾滋病毒感染者、有移民背景的人、有稳定伴侣的人、有更大的艾滋病毒相关担忧、消极的艾滋病毒相关情绪和更好的艾滋病毒理解的人中更高。艾滋病毒感染者、拥有学士学位的人、有移民背景的人、有稳定伴侣的人、以及认为艾滋病毒相关症状更严重、对艾滋病毒的担忧和负面情绪加剧的人寻求信息的频率更高。结论:虽然存在适度的意识,但参与仍然是被动的,信息寻求有限;然而,人们对治愈的极大兴趣凸显了加强沟通努力以促进包容性艾滋病毒治愈发展的必要性。
{"title":"Relatively high interest but limited active engagement in HIV cure research: Awareness, interest, and information-seeking among affected communities in the Netherlands.","authors":"Maaike A J Noorman, John B F de Wit, Tamika A Marcos, Sarah E Stutterheim, Thijs Albers, Kai J Jonas, Chantal den Daas","doi":"10.1016/j.jve.2024.100570","DOIUrl":"https://doi.org/10.1016/j.jve.2024.100570","url":null,"abstract":"<p><strong>Background: </strong>Community engagement is important for inclusive HIV cure development. This study evaluates current engagement in HIV cure research among affected communities in the Netherlands by analyzing awareness, interest, and information-seeking behavior. It also identifies participant characteristics and HIV-related illness perceptions linked to each engagement stage.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted from July 2023 to March 2024, involving 499 people with HIV and 578 individuals without HIV, including partners and gay, bisexual, and other men who have sex with men. Multivariate regression analyses examined the relationships between participant characteristics, HIV-related illness perceptions, and three outcomes: awareness, interest, and information-seeking.</p><p><strong>Results: </strong>The mean awareness was 3.08 (SD = 0.99) interest was higher at 3.67 (SD = 0.85), while the information-seeking frequency was lower at 2.33 (SD = 0.97). Higher awareness was seen in older participants, non-cisgender men, and those with increased perceived control and comprehensibility of HIV. Interest in cure research was higher among people with HIV, those with a migration background, individuals with steady partner(s), and those experiencing greater HIV-related concerns, negative HIV-related emotions, and better HIV comprehension. Information-seeking frequency was greater among people with HIV, those with a bachelor's degree, individuals from a migration background, those with steady partner(s), and those perceiving more severe HIV-related symptoms, and heightened concerns and negative emotions about HIV.</p><p><strong>Conclusion: </strong>While moderate awareness exists, engagement remains passive with limited information-seeking; however, significant interest in a cure underscores the need for enhanced communication efforts to foster inclusive HIV cure development.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100570"},"PeriodicalIF":3.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term outcome in people who use drugs successfully treated for hepatitis C infection with glecaprevir/pibrentasvir. 使用glecaprevir/pibrentasvir成功治疗丙型肝炎感染者的长期结果。
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-03 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100569
Shana Yi, David Truong, Brian Conway
<p><strong>Background: </strong>Several clinical trials, including the recently published the GRAND PLAN study from Vancouver Infectious Diseases Center (VIDC), have demonstrated the efficacy of hepatitis C (HCV) therapy among active drug users, including those facing significant addiction-related and social challenges. In the GRAND PLAN, we documented sustained virological response post-treatment Week12 (SVR12) in 108/117 (92.3 %) individuals (108/111 (mITT) or 97.3 % of those reaching the SVR12 timepoint) receiving an 8-week course of glecaprevir/pibrentasvir (G/P), with almost all using fentanyl and over half being unstably housed. Data on the maintenance of this favorable outcome in the long-term in such a population with a significant risk of reinfection is limited. We hypothesized that the offer of ongoing multidisciplinary care (including addiction care) after SVR12 was achieved would reduce the likelihood of loss to follow up, HCV reinfection or death and consolidate the gains achieved by initial engagement in care to diagnose and treat HCV infection.</p><p><strong>Methods: </strong>The inception cohort for this analysis was the 108 individuals achieving a cure of HCV infection within the GRAND PLAN study. All were offered the opportunity to continue to receive care at the VIDC. This is a multidisciplinary model of care to address medical, mental health, social and addiction-related concerns on an ongoing basis. This included, if necessary, opiate agonist and safer supply therapy, usually provided by the pharmacy adjacent to our inner-city campus. Among those choosing to be retained in care, the endpoint of this analysis was loss to follow up, mortality and HCV reinfection and their correlates. Reinfection was ascertained by repeat HCV RNA testing every 6 months, more frequently if clinically indicated.</p><p><strong>Results: </strong>Of the 108 individuals making up the inception cohort for this analysis, all chose to remain in care at the VIDC. We note a median age of 47 (22-75) years, 28 % female, 21.3 % identifying as indigenous, the majority with mild fibrosis (90.8 % F0-F2), slightly more than half with unstable housing. It is of note that we recorded a 20 % decrease in fentanyl users among those who were cured compared to the baseline evaluation of the overall study cohort (73.5 % vs 94.9 %, p < 0.000001). Among the cured individuals, 104 (96.3 %) remained alive, while 4 individuals died of opioid overdoses. Out of the 104 , 99 (95.2 %) remained HCV-free, while 5 (4.8 %) were re-infected. All five have recently initiated repeat HCV therapy at VIDC, 2 of whom are already documented to be cured.</p><p><strong>Conclusion: </strong>Among a population of vulnerable inner-city residents cured of HCV infection within a multidisciplinary program of care at the VIDC, all individuals accepted the offer to remain in long-term follow up, with a statistically significant reduction in fentanyl use over time. In the setting of an ongoing opioid c
背景:几项临床试验,包括最近发表的温哥华传染病中心(VIDC)的GRAND PLAN研究,已经证明了丙型肝炎(HCV)治疗对活跃吸毒者的疗效,包括那些面临严重成瘾相关和社会挑战的吸毒者。在GRAND PLAN中,我们记录了108/117(92.3%)人(108/111 (mITT)或97.3%达到SVR12时间点的人)在接受8周疗程的glecaprevir/pibrentasvir (G/P)治疗后第12周(SVR12)持续的病毒学反应,几乎所有人都使用芬太尼,超过一半的人居住不稳定。在这样一个具有显著再感染风险的人群中,长期维持这一有利结果的数据是有限的。我们假设,在达到SVR12后提供持续的多学科护理(包括成瘾护理)将降低随访损失、丙型肝炎病毒再感染或死亡的可能性,并巩固最初参与诊断和治疗丙型肝炎病毒感染所取得的成果。方法:本分析的初始队列是GRAND PLAN研究中治愈HCV感染的108例个体。所有人都有机会继续在VIDC接受治疗。这是一种多学科的护理模式,旨在持续解决医疗、心理健康、社会和成瘾相关问题。这包括,如有必要,阿片类激动剂和更安全的供应治疗,通常由我们市中心校园附近的药房提供。在那些选择继续护理的患者中,本分析的终点是失去随访、死亡率和丙型肝炎病毒再感染及其相关因素。通过每6个月重复HCV RNA检测来确定再感染,如果有临床指征则更频繁。结果:在本分析的初始队列中,108名个体均选择继续在VIDC接受治疗。我们注意到患者的中位年龄为47岁(22-75岁),28%为女性,21.3%为土著,大多数为轻度纤维化(90.8%为F0-F2),略多于一半的患者住房不稳定。值得注意的是,与总体研究队列的基线评估相比,我们记录到治愈的芬太尼使用者减少了20% (73.5% vs 94.9%, p结论:在VIDC的多学科护理计划中治愈了HCV感染的弱势市中心居民人群中,所有人都接受了继续进行长期随访的建议,随着时间的推移,芬太尼的使用有统计学意义的显著减少。在持续发生阿片类药物危机的情况下,在研究人群居住的社区每天记录3例死亡,我们记录了4例死亡。再次感染的发生率非常低,维持护理可以及时重新治疗,2/5的病例已经治愈,其他3人继续在VIDC接受HCV治疗。
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引用次数: 0
Real-life study on the effectiveness and safety of sofosbuvir/velpatasvir-based antiviral agents for hepatitis C eradication in Chinese patients. 基于索非布韦/维帕他韦的抗病毒药物在中国丙型肝炎患者根除中的有效性和安全性的现实研究。
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-12-03 eCollection Date: 2024-12-01 DOI: 10.1016/j.jve.2024.100571
Jiayi Wang, Lingyao Du, Dongmei Zhang, Chen Zhou, Yilan Zeng, Miao Liu, Xing Cheng, Xiaona Song, Han Chen, Ning Han, Enqiang Chen, Hong Tang

Background: Hepatitis C virus (HCV) eradication with sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, hepato-cellular carcinoma (HCC), or HCV/hepatitis B (HBV), HCV/HIV, or HCV/HBV/HIV coinfection.

Methods: In this real-world prospective observational study, we recruited patients from the West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults with with CHC and any genotype (GT), with or without cirrhosis, hepatocellular carcinoma (HCC), HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered SOF/VEL (400/100 mg) ± ribavirin (RBV) once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). Adverse events (AEs) were evaluated during treatment.

Results: The study included 483 patients with HCV genotypes 1, 2, 3, 6 and uncertain ones. Among them, 35.4 % (171/483, ITT) and 36.7 % (166/452, mITT) received SOF/VEL + RBV. At the end of treatment , 99.2 % (ITT, 479/483) and 99.1 % (mITT, 448/452) of patients had undetectable HCV RNA. SVR12 rates were 92.8 % [intention to treat (ITT), 448/483] and 99.1 % [modified ITT (mITT), 448/452]. In the mITT analysis, SVR12 for patients with HCV GT3b, those with cirrhosis or HCC, and those coinfected with HBV/HIV was 99.2 % (130/131), 99.4 % (168/169), and 97.6 % (40/41), respectively. The albumin-bilirubin (ALBI) (-3.01 vs. -3.18 P < 0.001), Fibrosis-4 (FIB4) Index (2.53 vs. 1.88, P = 0.004) and AST to Platelet Ratio Index (APRI) (0.99 vs. 0.44, P < 0.001) scores showed a significant decrease from baseline to SVR12. No patients experienced grade 3-5 AEs.

Conclusions: Although a high proportion of patients included in this study had HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection, SOF/VEL ± RBV was highly effective and well tolerated in Chinese patients with CHC.

背景:索非布韦/维帕他韦(SOF/VEL)根除丙型肝炎病毒(HCV)是一项重大进展,为在不同患者群体中消除病毒提供了希望。但在中国慢性丙型肝炎(CHC)患者,特别是HCV GT3b、肝硬化、肝细胞癌(HCC)、HCV/乙型肝炎(HBV)、HCV/HIV或HCV/HBV/HIV合并感染的患者,其有效性和安全性的真实数据仍然很少。方法:在这项现实世界的前瞻性观察研究中,我们从中国成都华西医院和公共卫生临床中心招募了患者。患者包括患有CHC和任何基因型(GT)的成年人,伴有或不伴有肝硬化、肝细胞癌(HCC)、HCV/HBV、HCV/HIV或HCV/HBV/HIV合并感染。患者给予SOF/VEL (400/100 mg)±利巴韦林(RBV),每日1次,连续12周。主要疗效终点是治疗后第12周的持续病毒学应答(SVR12)。在治疗期间评估不良事件(ae)。结果:纳入HCV基因型1、2、3、6及不确定型患者483例。其中,35.4% (171/483,ITT)和36.7% (166/452,mITT)接受了SOF/VEL + RBV治疗。在治疗结束时,99.2% (ITT, 479/483)和99.1% (mITT, 448/452)的患者无法检测到HCV RNA。SVR12率为92.8%[意向治疗(ITT), 448/483]和99.1%[改良ITT (mITT), 448/452]。在mITT分析中,HCV GT3b患者、肝硬化或HCC患者和HBV/HIV合并感染患者的SVR12分别为99.2%(130/131)、99.4%(168/169)和97.6%(40/41)。白蛋白-胆红素(ALBI) (-3.01 vs. -3.18 P vs. 1.88, P = 0.004)和AST /血小板比值指数(APRI) (0.99 vs. 0.44, P)结论:尽管本研究中有很高比例的患者患有HCV GT3b、肝硬化、HCC或HCV/HBV、HCV/HIV或HCV/HBV/HIV合并感染,SOF/VEL±RBV对中国CHC患者非常有效且耐受性良好。
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引用次数: 0
Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study 比利时一项前瞻性队列研究对艾滋病毒急性感染期间的免疫--静脉动态进行分期
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.jve.2024.100392
Jozefien De Clercq , Marie-Angélique De Scheerder , Sophie Vanherrewege , Els Caluwé , Nathalie Moreels , Danny Delooze , Annemieke Dhondt , Marc Coppens , Stefaan J. Vandecasteele , Sabine D. Allard , Coca Necsoi , Stéphane De Wit , Sarah Gerlo , Linos Vandekerckhove

Background

The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues.

Materials and methods

The ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI. The aim of the cohort is to study the impact of ART initiation during AHI on HIV reservoir and immune dysfunction in peripheral blood and anatomical sanctuary sites, as well as its effect on the gut microbiome. The cohort consists of two HBM sampling trajectories: one limited (blood, stool and leukapheresis) and a more extensive one (blood, stool, leukapheresis, colonoscopy, inguinal lymph node excision and lumbar puncture). Here we describe the baseline characteristics, immunovirological outcomes, safety and tolerability of HBM sampling.

Results

Between March 2016 and April 2024, 47 participants were enrolled, predominantly men who have sex with men (MSM), with a median age of 36 years [IQR 30–43.5]. Almost 90 % of participants initiated ART within 72 h after study inclusion, irrespective of HBM sampling trajectory. The timing of ART initiation according to the Fiebig stage did not significantly impact immune recovery (CD4/CD8 ratio ≥1) or the time to viral suppression. Approximately 40 % of participants opted for the extensive HBM sampling trajectory during AHI. However, the participation rate for the extensive trajectory decreased by nearly half at the longitudinal follow-up timepoint. In general, study-related procedures were safe and well-tolerated, with limited procedure-related adverse events (AEs). Inguinal lymph node excision was associated with the highest AE rate, in line with previous reports.

Conclusions

Our findings reaffirm the beneficial effect of ART initiation during AHI on long term immunovirological outcomes, regardless of Fiebig stage at treatment initiation. Additionally, we demonstrate that the collection of HBM during and longitudinally after AHI is safe and feasible, without compromising time to ART initiation. Cohorts that integrate comprehensive clinical data with high-quality HBM samples are essential to longitudinally study the impact of early ART on reservoir dynamics and immune responses across various anatomical sites after AHI.
背景HIV急性感染(AHI)期间发生的事件为随后的病程奠定了基础。材料与方法 ACS队列是比利时的一项前瞻性队列研究,它收集了在急性艾滋病感染期间接受诊断和治疗的患者的纵向临床数据和人体材料(HBM)。该队列的目的是研究在 AHI 期间开始抗逆转录病毒疗法对外周血和解剖禁区部位的艾滋病病毒库和免疫功能障碍的影响,以及对肠道微生物组的影响。该队列由两个 HBM 采样轨迹组成:一个是有限的采样轨迹(血液、粪便和白细胞),另一个是更广泛的采样轨迹(血液、粪便、白细胞、结肠镜检查、腹股沟淋巴结切除术和腰椎穿刺术)。结果在 2016 年 3 月至 2024 年 4 月期间,47 名参与者入组,主要是男男性行为者(MSM),中位年龄为 36 岁[IQR 30-43.5]。近 90% 的参与者在纳入研究后 72 小时内开始接受抗逆转录病毒疗法,与 HBM 采样轨迹无关。根据 Fiebig 阶段开始抗逆转录病毒疗法的时间对免疫恢复(CD4/CD8 比率≥1)或病毒抑制时间没有显著影响。大约 40% 的参与者在 AHI 期间选择了广泛的 HBM 采样轨迹。然而,在纵向随访时间点,广泛采样轨迹的参与率下降了近一半。总体而言,与研究相关的手术安全且耐受性良好,与手术相关的不良事件(AEs)有限。结论我们的研究结果再次证实了在 AHI 期间开始抗逆转录病毒疗法对长期免疫病理结果的有利影响,无论开始治疗时的 Fiebig 阶段如何。此外,我们还证明了在 AHI 期间和 AHI 后纵向收集 HBM 是安全可行的,不会影响开始抗逆转录病毒疗法的时间。综合全面的临床数据和高质量的 HBM 样本的队列对于纵向研究早期抗逆转录病毒疗法对 AHI 后不同解剖部位储库动态和免疫反应的影响至关重要。
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引用次数: 0
Partner protections in HIV cure-related trials involving analytical treatment interruption: Updated toolkit to mitigate HIV transmission risk 在涉及分析性治疗中断的艾滋病治愈相关试验中保护合作伙伴:降低艾滋病毒传播风险的最新工具包
IF 3.5 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.jve.2024.100386
Karine Dubé , Thomas J. Villa , William Freshwater , Brittney Mauk , Annette Rid , Michael J. Peluso
Analytical treatment interruptions (ATIs) are widely used to evaluate HIV cure-related research interventions. However, sex partners of cure-related trial participants might be at risk of acquiring HIV during ATIs. Addressing this risk is key to ensuring the continued success of trials involving ATIs and offer greater acceptability across multiple trials sites. In 2022, the Advancing Clinical Therapeutics Globally (ACTG) Network convened a Partner Protections Working Group (PPWG) to update the 2020 HIV transmission risk toolkit developed by Peluso and colleagues. In our review of the original toolkit, we identified new challenges and needs at the participant, partner and study levels, as well as new evidence on measures to address these needs and more advanced ethical thinking on partner protections in HIV cure-related trials with ATIs. Based on these findings, we developed an updated toolkit that will provide trial participants and their partners with better support to address new and unfamiliar situations and protect partners from undue harm. We present this toolkit, make it available as a resource for cure-related trials with ATIs and discuss possible future directions.
分析性治疗中断(ATI)被广泛用于评估与艾滋病治愈相关的研究干预措施。然而,与治愈相关的试验参与者的性伴侣可能有在 ATI 期间感染 HIV 的风险。解决这一风险是确保涉及 ATIs 的试验持续成功的关键,并能为多个试验点提供更高的可接受性。2022 年,全球推进临床治疗(ACTG)网络召集了合作伙伴保护工作组(PPWG),以更新 Peluso 及其同事开发的 2020 年 HIV 传播风险工具包。在对原始工具包的审查中,我们发现了参与者、伴侣和研究层面的新挑战和新需求,以及解决这些需求的措施的新证据和在使用 ATIs 的 HIV 治愈相关试验中伴侣保护方面更先进的伦理思想。基于这些发现,我们开发了一个更新的工具包,为试验参与者及其伴侣提供更好的支持,以应对新的和陌生的情况,并保护伴侣免受不必要的伤害。我们将介绍该工具包,将其作为ATIs治愈相关试验的资源,并讨论未来可能的发展方向。
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引用次数: 0
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Journal of Virus Eradication
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