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Exposure to angiotensin-converting enzyme inhibitors that cross the blood-brain barrier and the risk of dementia among People Living with HIV. 接触可穿过血脑屏障的血管紧张素转换酶抑制剂与艾滋病病毒感染者患痴呆症的风险。
IF 3.8 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-10 DOI: 10.1097/qad.0000000000004009
Tammy H Cummings,Joseph Magagnoli,Sasha Sikirzhytskaya,Ilya Tyagin,Ilya Safro,Michael D Wyatt,Michael Shtutman,S Scott Sutton
BACKGROUNDThe decreased mortality of people living with HIV (PLWH) has revealed non-HIV-associated comorbidities such as neurocognitive disorders (e.g., dementia). There is an urgency to discover therapeutics to prevent or delay neurocognitive decline among PLWH.METHODSThe artificial intelligence platform Automatic Graph-mining And Transformer based Hypothesis Generation Approach (AGATHA) was utilized to seek potential drugs to be repurposed for the management of non-HIV-associated dementia. AGATHA revealed angiotensin-converting enzyme inhibitors that cross the blood-brain barrier (BBB ACEi) as a target for decreasing dementia. Subsequently, we conducted a retrospective study evaluating incident dementia using the VA Informatics and Computing Infrastructure (VINCI) evaluating ACE inhibitors. Cox proportional hazards models were fit and hazard ratios (HR) with corresponding 95% confidence intervals (CIs) are presented.FINDINGSA total 9,419 PLWH exposed to an BBB ACE inhibitor (ACEi) and 8,831 PLWH unexposed demonstrated that PLWH exposed to BBB ACEi had a 21.4% (univariate) and 15.2% (multivariate) lower hazard of dementia. The propensity score matched analysis demonstrated a 14.3% lower hazard of incident dementia compared to BBB ACEi unexposed (HR 0.857, 95% CI 0.747-0.984).INTERPRETATIONAn artificial intelligence-based literature mining system (AGATHA) was utilized to uncover a medication with potential to be repurposed. AGATHA demonstrated that BBB ACEi as a target for decreasing dementia among PLWH. Additionally, we conducted a retrospective study demonstrating a decrease in incident dementia among PLWH exposed to BBB ACEi. Future research is needed to explore further and understand the relationship of dementia among PLWH exposed to ACEi.
背景艾滋病毒感染者(PLWH)死亡率的下降揭示了非艾滋病毒相关的合并症,如神经认知障碍(如痴呆症)。方法利用人工智能平台 "基于自动图形挖掘和变换器的假设生成方法"(AGATHA)来寻找潜在药物,以便将其重新用于治疗非艾滋病毒相关性痴呆症。AGATHA 发现,可穿过血脑屏障(BBB ACEi)的血管紧张素转换酶抑制剂是减少痴呆症的目标药物。随后,我们利用退伍军人信息学和计算基础设施(VINCI)对ACE抑制剂进行了一项回顾性研究,评估了痴呆症的发病情况。研究结果显示,共有 9,419 名 PLWH 暴露于 BBB ACE 抑制剂(ACEi),8,831 名 PLWH 未暴露于该抑制剂,结果表明,暴露于 BBB ACEi 的 PLWH 痴呆症风险降低了 21.4%(单变量)和 15.2%(多变量)。基于人工智能的文献挖掘系统(AGATHA)被用来发现一种具有再利用潜力的药物。AGATHA 表明,BBB ACEi 是减少 PLWH 中痴呆症的目标。此外,我们还进行了一项回顾性研究,结果表明,接触过 BBB ACEi 的 PLWH 中发生痴呆症的人数有所减少。未来的研究需要进一步探索和了解暴露于 ACEi 的 PLWH 中痴呆症的关系。
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引用次数: 0
Transition to dolutegravir-based ART in 35 low- and middle-income countries: a global survey of HIV care clinics. 35 个中低收入国家向基于多罗替拉韦的抗逆转录病毒疗法的过渡:对艾滋病毒护理诊所的全球调查。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1097/QAD.0000000000004007
Elizabeth Zaniewski, Veronika Whitesell Skrivankova, Ellen Brazier, Anchalee Avihingsanon, Sandra Wagner Cardoso, Carina Cesar, Henri Chenal, Brenda E Crabtree-Ramírez, Rossana A Ditangco, Peter Vanes Ebasone, Brian Eley, Jonathan George Euvrard, Geoffrey Fatti, Jacqueline Madalitso Huwa, Patricia Lelo, Daisy Maria Machado, Eugene Kouassi Messou, Albert Kla Minga, Joseph Muleebwa, Sanjay Mundhe, Gad Murenzi, Winnie R Muyindike, Dominique Mahambou Nsonde, Sarah M Obatsa, Joseph Odhiambo, Hans Walter Prozesky, Supattra Rungmaitree, Aggrey Semwendero Semeere, Moussa Seydi, Nosisa Sipambo, Tavitiya Sudjaritruk, Karl-Günter Technau, Thierry Tiendrebeogo, Christelle Twizere, Marie Ballif

Objective: We studied the transition to dolutegravir-containing antiretroviral therapy (ART) at HIV treatment clinics within the International epidemiology Databases to Evaluate AIDS (IeDEA).

Design: Site-level survey conducted in 2020-2021 among HIV clinics in low- and middle-income countries (LMICs).

Methods: We assessed the status of dolutegravir rollout and viral load and drug resistance testing practices for patients on ART switching to dolutegravir-based regimens. We used generalized estimating equations to assess associations between clinic rollout of both first- and second-line dolutegravir-based ART regimens (dual rollout) and site-level factors.

Results: Of 179 surveyed clinics, 175 (98%) participated; 137 (78%) from Africa, 30 (17%) from the Asia-Pacific, and 8 (5%) from Latin America. Most clinics (80%) were in low- or lower-middle-income countries, and there were a mix of primary-, secondary- and tertiary-level clinics. Ninety percent reported rollout of first-line dolutegravir, 59% of second-line, 94% of first- or second-line and 55% of dual rollout. The adjusted odds of dual rollout were higher among tertiary-level (aOR 4.00; 95% CI 1.39 to 11.47) and secondary-level clinics (aOR 3.66; 95% CI 2.19 to 6.11) than in primary-level clinics. Over half (59%) of clinics that introduced first- or second-line dolutegravir-based ART required recent viral load testing before switching to dolutegravir, and 15% performed genotypic resistance testing at switch.

Conclusions: Dolutegravir-based ART was rolled out at nearly all IeDEA clinics in LMICs, yet many switched patients to dolutegravir without recent viral load testing and drug resistance testing was rarely performed. Without such testing, drug resistance among patient switching to dolutegravir may go undetected.

目的我们研究了国际艾滋病流行病学评估数据库(IeDEA)中的艾滋病治疗诊所向含多罗替韦的抗逆转录病毒疗法(ART)过渡的情况:设计:2020-2021 年在中低收入国家(LMICs)的 HIV 诊所进行的现场调查:我们评估了多罗替拉韦的推广情况以及接受抗逆转录病毒疗法的患者转用多罗替拉韦治疗方案后的病毒载量和耐药性检测情况。我们使用了广义估计方程来评估诊所同时推广基于多鲁特韦的一线和二线抗逆转录病毒疗法(双线推广)与地点水平因素之间的关联:在 179 家接受调查的诊所中,175 家(98%)参与了调查;其中 137 家(78%)来自非洲,30 家(17%)来自亚太地区,8 家(5%)来自拉丁美洲。大多数诊所(80%)位于低收入或中低收入国家,其中包括初级、二级和三级诊所。90%的诊所报告推出了一线多鲁曲韦,59%的诊所推出了二线多鲁曲韦,94%的诊所推出了一线或二线多鲁曲韦,55%的诊所推出了双线多鲁曲韦。三级诊所(aOR 4.00;95% CI 1.39 至 11.47)和二级诊所(aOR 3.66;95% CI 2.19 至 6.11)的调整后双线推广几率高于一级诊所。在引入基于多鲁曲韦的一线或二线抗逆转录病毒疗法的诊所中,超过一半(59%)的诊所要求在转用多鲁曲韦之前进行近期病毒载量检测,15%的诊所在转用时进行了基因型耐药性检测:结论:在低收入发展中国家,几乎所有的 IeDEA 诊所都推出了基于多鲁曲韦的抗逆转录病毒疗法,但许多诊所在未进行近期病毒载量检测的情况下就将患者转为使用多鲁曲韦,而且很少进行耐药性检测。如果不进行此类检测,转用多鲁特韦的患者的耐药性可能不会被发现。
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引用次数: 0
Low food security is associated with frailty status and frailty components among people with HIV. 食物保障不足与艾滋病毒感染者的虚弱状况和虚弱成分有关。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-04 DOI: 10.1097/QAD.0000000000004006
Stephanie A Ruderman, Amanda L Willig, John D Cleveland, Greer Burkholder, Christine Horvat Davey, Julia Fleming, Barbara Gripshover, Mari Katundu, Thomas W Buford, Raymond Jones, Michael S Saag, Joseph A C Delaney, Heidi M Crane, Allison R Webel

Background: Low food security is common among people with HIV (PWH) and is associated with poorer health outcomes. Frailty, an aging-related outcome that is increasingly prevalent among PWH, may be stimulated by low food security. We assessed associations between food security and frailty among PWH.

Methods: The Impact of Physical Activity Routines and Dietary Intake on the Longitudinal Symptom Experience of People Living with HIV (PROSPER-HIV) study follows PWH to evaluate how diet and physical activity impact symptoms. We utilized food security and frailty data from PROSPER-HIV Year 1 visits (January 2019 to July 2022) to estimate associations. Food security was measured via the validated two-item Food Security Questionnaire and categorized as Food Secure, Low Food Security, or Very Low Food Security. Frailty was measured with the Fried frailty phenotype, and categorized as robust, prefrail, and frail. We used relative risk regression to estimate associations between food security and frailty status, adjusted for demographic characteristics.

Results: Among 574 PWH, nearly one-quarter were women (22%), mean age was 52 years old, 8% were frail, and 46% prefrail. Low food security was reported among nearly one-third of PWH: 13% Low Food Security and 18% Very Low Food Security. Compared with being Food Secure, we found Low Food Security was associated with frailty [prevalence ratio: 4.06 (95% confidence interval (CI) 2.16-7.62] and Very Low Food Security was associated with both prefrailty [1.48 (1.23-1.78)] and frailty [5.61 (3.14-10.0)], as compared with robust status.

Conclusion: Low food security was associated with increased frailty among PWH in this study, suggesting a potential intervention point to promote healthy aging.

背景:在艾滋病病毒感染者(PWH)中,低食品安全很常见,而且与较差的健康结果有关。虚弱是一种与衰老相关的结果,在艾滋病感染者中越来越普遍,而低食品安全可能会刺激这种结果。我们评估了食品安全与虚弱之间的关系:体力活动常规和饮食摄入对艾滋病病毒感染者纵向症状体验的影响(PROSPER-HIV)研究对艾滋病病毒感染者进行跟踪调查,以评估饮食和体力活动对症状的影响。我们利用 PROSPER-HIV 第 1 年访问(2019 年 1 月至 2022 年 7 月)中的食品安全和虚弱数据来估算相关性。食物安全通过经过验证的两项目食物安全问卷进行测量,并分为食物安全、低食物安全或极低食物安全。虚弱程度通过弗里德虚弱表型进行测量,分为健壮、虚弱前和虚弱。我们使用相对风险回归法来估计食物保障和虚弱状态之间的关系,并对人口特征进行了调整:在 574 名残疾人中,近四分之一为女性(22%),平均年龄为 52 岁,8% 为体弱者,46% 为前体弱者。据报告,近三分之一的残疾人的食物保障程度较低:13%的人食物保障程度较低,18%的人食物保障程度非常低。与 "粮食安全 "相比,我们发现 "低粮食安全 "与体弱[患病率比:4.06(95% 置信区间(CI):2.16-7.62]]相关,而与 "健康状况 "相比,"极低粮食安全 "与体弱[1.48(1.23-1.78)]和体弱[5.61(3.14-10.0)]相关:结论:在这项研究中,低食品安全与威利人的虚弱程度增加有关,表明这是促进健康老龄化的一个潜在干预点。
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引用次数: 0
Changes in HIV Pre-exposure Prophylaxis Awareness and Use Among Males Who Inject Drugs Who Have Sex with Men by Sexual Identity, 19 US Urban Areas, 2018 & 2022. 2018 年和 2022 年美国 19 个城市地区注射毒品并与男性发生性关系的男性对艾滋病毒暴露前预防措施的认识和使用情况变化(按性取向分列)。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-03 DOI: 10.1097/QAD.0000000000004005
Patrick C Eustaquio, Janet Burnett, Joseph Prejean, Johanna Chapin-Bardales, Susan Cha

Background: Men who inject drugs who have sex with men (MWIDSM) may acquire HIV through injecting drugs or sex. Interventions to increase awareness of HIV preexposure prophylaxis (PrEP) have focused on gay/bisexual MSM and may not be reaching heterosexual-identifying men or people who inject drugs (PWID). We explored changes in PrEP awareness and use among MWIDSM from 2018 to 2022 by sexual identity.

Methods: We used data from the 2018 and 2022 National HIV Behavioral Surveillance among PWID recruited via respondent-driven sampling in 19 urban areas in the US. We examined changes in PrEP awareness and use over time by sexual identity among HIV-negative men who inject drugs and who had sex with another man in the past 12 months using log-linked Poisson regression models with robust standard errors with an interaction term between year and sexual identity.

Results: Among 758 HIV-negative MWIDSM (463 in 2018; 295 in 2022), nearly all sample participants were likely indicated for PrEP (94.2 and 92.9%, respectively). PrEP awareness increased from 2018 to 2022 among gay/bisexual-identifying MWIDSM [45.5-65.5%; aPR = 1.49, 95% confidence interval (95% CI) = 1.30-1.70] but remained stable for heterosexual-identifying MWIDSM (39.4-40.8%; aPR = 1.01, 95% CI 0.75-1.36). PrEP use remained low among all MWIDSM (2.5-7.7%, among heterosexually identifying; 15.3 to 10.2% among gay/bisexual-identifying).

Conclusion: PrEP awareness increased among gay/bisexual-identifying MWIDSM but not among heterosexual-identifying. PrEP use was low for all MWIDSM. Public health initiatives catered to MWIDSM should focus on improved campaigns and expanding PrEP accessibility in existing healthcare, harm reduction, and social services.

背景:男男性行为者(MWIDSM)可能会通过注射毒品或性行为感染艾滋病毒。为提高人们对艾滋病暴露前预防(PrEP)的认识而采取的干预措施主要针对男同性恋/双性恋 MSM,可能无法惠及认同异性恋的男性或注射吸毒者(PWID)。我们探讨了从 2018 年到 2022 年,MWIDSM 对 PrEP 的认识和使用情况在性别认同方面的变化:我们使用了 2018 年和 2022 年全国艾滋病毒行为监测的数据,这些数据来自美国 19 个城市地区通过受访者驱动的抽样调查招募的 PWID。我们使用具有稳健标准误差的对数链接泊松回归模型,并在年份和性身份之间加入交互项,研究了过去 12 个月中与另一名男性发生过性关系的 HIV 阴性男性注射吸毒者中,随着时间的推移,不同性身份的人对 PrEP 的认识和使用情况的变化:在 758 名 HIV 阴性的 MWIDSM 中(2018 年 463 人;2022 年 295 人),几乎所有样本参与者都可能有 PrEP 适应症(分别为 94.2% 和 92.9%)。从 2018 年到 2022 年,同性恋/双性恋认同的 MWIDSM 对 PrEP 的认知度有所提高[45.5%-65.5%;aPR = 1.49,95% 置信区间 (95% CI) = 1.30-1.70],但异性恋认同的 MWIDSM 对 PrEP 的认知度保持稳定(39.4%-40.8%;aPR = 1.01,95% CI 0.75-1.36)。在所有女性同性恋、双性恋和变性者中,PrEP 的使用率仍然很低(异性恋认同者为 2.5%-7.7%;同性恋/双性恋认同者为 15.3%-10.2%):结论:在认同同性恋/双性恋的女性艾滋病患者中,对 PrEP 的认识有所提高,但在认同异性恋的女性艾滋病患者中却没有提高。在所有女性同性恋、双性恋和变性者中,PrEP 的使用率都很低。针对女性同性恋、双性恋和变性者的公共卫生措施应侧重于改进宣传活动,并在现有的医疗保健、减低伤害和社会服务中扩大 PrEP 的可及性。
{"title":"Changes in HIV Pre-exposure Prophylaxis Awareness and Use Among Males Who Inject Drugs Who Have Sex with Men by Sexual Identity, 19 US Urban Areas, 2018 & 2022.","authors":"Patrick C Eustaquio, Janet Burnett, Joseph Prejean, Johanna Chapin-Bardales, Susan Cha","doi":"10.1097/QAD.0000000000004005","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004005","url":null,"abstract":"<p><strong>Background: </strong>Men who inject drugs who have sex with men (MWIDSM) may acquire HIV through injecting drugs or sex. Interventions to increase awareness of HIV preexposure prophylaxis (PrEP) have focused on gay/bisexual MSM and may not be reaching heterosexual-identifying men or people who inject drugs (PWID). We explored changes in PrEP awareness and use among MWIDSM from 2018 to 2022 by sexual identity.</p><p><strong>Methods: </strong>We used data from the 2018 and 2022 National HIV Behavioral Surveillance among PWID recruited via respondent-driven sampling in 19 urban areas in the US. We examined changes in PrEP awareness and use over time by sexual identity among HIV-negative men who inject drugs and who had sex with another man in the past 12 months using log-linked Poisson regression models with robust standard errors with an interaction term between year and sexual identity.</p><p><strong>Results: </strong>Among 758 HIV-negative MWIDSM (463 in 2018; 295 in 2022), nearly all sample participants were likely indicated for PrEP (94.2 and 92.9%, respectively). PrEP awareness increased from 2018 to 2022 among gay/bisexual-identifying MWIDSM [45.5-65.5%; aPR = 1.49, 95% confidence interval (95% CI) = 1.30-1.70] but remained stable for heterosexual-identifying MWIDSM (39.4-40.8%; aPR = 1.01, 95% CI 0.75-1.36). PrEP use remained low among all MWIDSM (2.5-7.7%, among heterosexually identifying; 15.3 to 10.2% among gay/bisexual-identifying).</p><p><strong>Conclusion: </strong>PrEP awareness increased among gay/bisexual-identifying MWIDSM but not among heterosexual-identifying. PrEP use was low for all MWIDSM. Public health initiatives catered to MWIDSM should focus on improved campaigns and expanding PrEP accessibility in existing healthcare, harm reduction, and social services.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Primary HPV screening compared with other cervical cancer screening strategies in women with HIV: a cost-effectiveness study. 感染艾滋病毒妇女的 HPV 初筛与其他宫颈癌筛查策略的比较:成本效益研究。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-02 DOI: 10.1097/QAD.0000000000004002
Ran Zhao, Erinn Sanstead, Fernando Alarid-Escudero, Megan Huchko, Michael Silverberg, Karen Smith-Mccune, Steven E Gregorich, Wendy Leyden, Miriam Kuppermann, George F Sawaya, Shalini Kulasingam

Objective: To compare the model-predicted benefits, harms, and cost-effectiveness of cytology, cotesting, and primary HPV screening in U.S. women living with HIV (WLWH).

Design: We adapted a previously published Markov decision model to simulate a cohort of U.S. WLWH.

Setting: United States.

Subjects, participants: A hypothetical inception cohort of WLWH.

Intervention: We simulated five screening strategies all assumed the same strategy of cytology with HPV triage for ASCUS for women aged 21 to 29 years. The different strategies noted are for women aged 30 and older as the following: continue cytology with HPV triage, cotesting with repeat cotesting triage, cotesting with HPV16/18 genotyping triage, primary hrHPV testing with cytology triage, and primary hrHPV testing with HPV16/18 genotyping triage.

Main outcome measures: The outcomes include colposcopies, false-positive results, treatments, cancers, cancer deaths, life-years and costs, and lifetime quality-adjusted life-years.

Results: Compared with no screening, screening was cost-saving, and > 96% of cervical cancers and deaths could be prevented. Cytology with HPV triage dominated primary HPV screening and cotesting. At willingness-to-pay thresholds under $250,000, probabilistic sensitivity analyses indicated that primary HPV testing was more cost-effective than cotesting in over 98% of the iterations.

Conclusions: Our study suggests the current cytology-based screening recommendation is cost-effective, but that primary HPV screening could be a cost-effective alternative to cotesting. To improve the cost-effectiveness of HPV-based screening, increased acceptance of the HPV test among targeted women is needed, as are alternative follow-up recommendations to limit the harms of high false-positive testing.

目的:比较美国女性艾滋病病毒感染者(WLWH)接受细胞学、共同检测和 HPV 初筛的益处、危害和成本效益:比较模型预测的美国女性艾滋病感染者(WLWH)细胞学检查、共同检测和 HPV 初筛的益处、危害和成本效益:设计:我们对之前发表的马尔科夫决策模型进行了改编,以模拟美国 WLWH 群体:背景:美国:干预措施:我们模拟了五种筛查策略:我们模拟了五种筛查策略,所有策略均假定对 21 至 29 岁的女性进行细胞学检查,并对 ASCUS 进行 HPV 分流。针对 30 岁及以上女性的不同策略如下:继续细胞学与 HPV 分流、重复细胞学与 HPV16/18 基因分型分流、初级 hrHPV 检测与细胞学分流、初级 hrHPV 检测与 HPV16/18 基因分型分流:结果包括阴道镜检查次数、假阳性结果、治疗、癌症、癌症死亡、生命年数和成本以及终生质量调整生命年数:结果:与不进行筛查相比,筛查可节约成本,96%以上的宫颈癌和死亡可以避免。带有 HPV 分流的细胞学检查在 HPV 初筛和联合检测中占主导地位。在支付意愿阈值低于250,000美元时,概率敏感性分析表明,在超过98%的迭代中,初级HPV检测比联合检测更具成本效益:我们的研究表明,目前以细胞学为基础的筛查建议具有成本效益,但初级 HPV 筛查可能是一种替代联合检测的具有成本效益的方法。为了提高基于HPV的筛查的成本效益,需要提高目标妇女对HPV检测的接受度,还需要提出替代性随访建议,以限制高假阳性检测的危害。
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引用次数: 0
Immune checkpoints and pancreatic beta cell dysfunction in HIV. 艾滋病毒的免疫检查点和胰腺β细胞功能障碍。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-01 DOI: 10.1097/QAD.0000000000003932
Luke A Pryke, Ziyue Liu, Alka K Khaitan, Emily K Sims, Samir K Gupta

We explored the impact of immune dysregulation on pancreatic beta cell injury in HIV patients. Analyzing 105 participant samples, we observed lower IL-21 levels and elevated immune checkpoint levels (e.g. PD-1, CD27+, CD40+) in untreated HIV patients. Notably, soluble TIM-3 correlated positively with improved beta cell function and inversely with beta cell stress, suggesting its potential role in beta cell protection in untreated HIV.

我们探讨了免疫失调对艾滋病患者胰腺β细胞损伤的影响。通过分析 105 例参与者样本,我们观察到未经治疗的 HIV 患者 IL-21 水平较低,免疫检查点水平(如 PD-1、CD27+、CD40+)升高。值得注意的是,可溶性 TIM-3 与β细胞功能的改善呈正相关,而与β细胞应激反应呈反相关,这表明它在未经治疗的 HIV 患者的β细胞保护中具有潜在作用。
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引用次数: 0
Impact of rosuvastatin on pulse-wave velocity in men with HIV at moderate cardiovascular risk. 罗伐他汀对中度心血管风险男性艾滋病患者脉搏波速度的影响。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-01 DOI: 10.1097/QAD.0000000000003930
Janine M Trevillyan, Anthony Dart, Eldho Paul, Elizabeth M Dewar, Victoria G Hall, Jennifer F Hoy

This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676].

这项双盲、随机、安慰剂对照试验的单中心子研究旨在确定服用罗伐他汀 96 周对中度心血管风险(弗雷明汉风险评分 10-15%)男性艾滋病患者(n = 55,54 岁)脉搏波速度(PWV)的影响。罗伐他汀治疗组[0.54 m/s 标准差(SED)0.26]和安慰剂治疗组[0.50 m/s (SED 0.26),P = 0.896]的脉搏波速度均有所增加,导致第 96 周时脉搏波速度无差异[罗伐他汀 9.40 m/s (SE 0.31);安慰剂 9.21 m/s (SE0.31), P = 0.676]。
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引用次数: 0
Association between switching to integrase strand transfer inhibitors and incident diabetes in people with HIV. 艾滋病病毒感染者转用整合酶链转移抑制剂与糖尿病发病之间的关系:一项纵向队列研究。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-11 DOI: 10.1097/QAD.0000000000003954
Y Joseph Hwang, Catherine R Lesko, Todd T Brown, G Caleb Alexander, Lauren C Zalla, Jeanne C Keruly, LaQuita N Snow, Jarratt D Pytell, Oluwaseun Falade-Nwulia, Joyce L Jones, Richard D Moore, Anthony T Fojo

Objective: Integrase strand transfer inhibitors (INSTI) are associated with weight gain in people with HIV (PWH), but their impact on diabetes is unclear. We evaluated the association between switching from nonnucleoside reverse-transcriptase inhibitors (NNRTI) or protease inhibitors (PI) to INSTI and incident diabetes.

Design: Longitudinal cohort study.

Methods: We included PWH aged ≥18 years from the Johns Hopkins HIV Clinical Cohort (2007-2023) without history of diabetes who had used NNRTI or PI for ≥180 days. We followed participants up to 10 years from HIV primary care visits where they switched to INSTI or continued NNRTI or PI. We estimated the hazard of incident diabetes associated with switching to INSTI using weighted Cox regression with robust variance estimator.

Results: We included 2075 PWH who attended 22 116 visits where they continued NNRTI or PI and 631 visits where they switched to INSTI. Switching to INSTI was associated with a weighted hazard ratio (wHR) of 1.11 [95% confidence interval (CI), 0.77-1.59] for incident diabetes. The association if no weight gain occurred during the first two years was not qualitatively different (wHR 1.22; 95% CI, 0.82-1.80). In a posthoc analysis, switching to INSTI conferred a significant wHR of 1.79 (95% CI, 1.13-2.84) for diabetes within the first two years but not after.

Conclusions: Switching from NNRTI or PI to INSTI did not significantly increase overall diabetes incidence in PWH, although there may be elevated risk in the first two years. These findings can inform considerations when switching to INSTI-based regimens.

目的:整合酶链转移抑制剂(INSTI)与艾滋病病毒感染者(PWH)体重增加有关,但其对糖尿病的影响尚不清楚。我们评估了从非核苷类逆转录酶抑制剂(NNRTI)或蛋白酶抑制剂(PI)转用INSTI与糖尿病发病之间的关系:设计:纵向队列研究:我们纳入了约翰霍普金斯大学 HIV 临床队列(2007-2023 年)中年龄≥18 岁、无糖尿病史、使用 NNRTI 或 PI ≥180 天的感染者。我们对转用 INSTI 或继续使用 NNRTI 或 PI 的参与者进行了长达 10 年的艾滋病初级保健随访。我们使用带稳健方差估计器的加权 Cox 回归估算了与改用 INSTI 相关的糖尿病发病风险:我们纳入了 2,075 名 PWH,他们在 22,116 次就诊中继续使用 NNRTI 或 PI,在 631 次就诊中改用 INSTI。改用 INSTI 与糖尿病的加权危险比 (wHR) 为 1.11(95% 置信区间 [CI],0.77-1.59)有关。如果前两年体重没有增加,则两者之间的关系没有本质区别(wHR 1.22;95% CI,0.82-1.80)。在一项事后分析中,改用INSTI后,头两年内糖尿病的wHR为1.79(95% CI,1.13-2.84),而两年后则没有显著差异:从 NNRTI 或 PI 转为 INSTI 并不会显著增加 PWH 的总体糖尿病发病率,尽管在最初两年内可能会有风险升高。这些发现可为改用基于 INSTI 的治疗方案提供参考。
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引用次数: 0
The construction of a novel supplementary diagnostic model for patients with indeterminate HIV infection. 为不确定的艾滋病病毒感染者构建新的辅助诊断模型:蛋白质组学研究。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-12 DOI: 10.1097/QAD.0000000000003977
Yajun Yan, Rui Yuan, Liping Deng, Hui Hu, Yong Yang, Xien Gui, Rongrong Yang

Introduction: The window period, defined as HIV nucleic acid test (NAT) reactivity but Western blot (WB) test inconclusive, is garnering more attention. Improving the detection efficiency of HIV high-risk populations in the window period is critical to reducing the risk of unanticipated transmission. The purpose of this study was to create an additional strategy for distinguishing indeterminate HIV infection cases.

Methods: Based on WB follow-up results, the individuals in this study were divided into persons in the HIV window period and persons without HIV. Plasma was analyzed using quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect differentially expressed proteins (DEPs). The biological implications of these DEPs were investigated using enrichment analysis. Protein-protein interaction (PPI) analysis and LASSO regression were used to identify key proteins. The calibration curve, decision curve, and nomogram were utilized to create the model.

Results: Fifty-seven DEPs were screened out, with 33 up-regulated and 24 down-regulated in persons with HIV at window period. The most important Gene Ontology (GO) enrichment items are oxidoreductase activity and heme binding. Oxidoreductases account for half of the 10 main proteins identified from various DEPs. An auxiliary diagnostic model comprised of peroxiredoxin-2 (P32119), band 3 anion transport protein (P02730), and histone H2A type 1 (P0C0S8) was developed. The results of the confusion matrix parameters revealed that this diagnostic approach had strong practicability in distinguishing indeterminate HIV infection cases.

Conclusions: The three DEPs identified and predicted by proteomics are useful for the supplemental identification of persons in the HIV window period.

导言:窗口期是指艾滋病病毒核酸检测(NAT)有反应,但西方印迹(WB)检测没有结果,这一阶段正受到越来越多的关注。提高窗口期 HIV 高危人群的检测效率对于降低意外传播风险至关重要。本研究的目的是为区分不确定的 HIV 感染病例提供一种额外的策略:方法:根据 WB 随访结果,本研究中的人被分为处于 HIV 窗口期的人和未感染 HIV 的人。使用定量液相色谱串联质谱法(LC-MS/MS)对血浆进行分析,以检测差异表达蛋白(DEPs)。利用富集分析研究了这些 DEPs 的生物学意义。蛋白质-蛋白质相互作用(PPI)分析和 LASSO 回归用于识别关键蛋白质。校准曲线、决策曲线和提名图被用来创建模型:结果:共筛选出 57 个 DEPs,其中 33 个上调,24 个下调。最重要的基因本体(GO)富集项是氧化还原酶活性和血红素结合。氧化还原酶占从各种 DEPs 中鉴定出的 10 种主要蛋白质的一半。由过氧化还原酶-2(P32119)、Band 3 阴离子转运蛋白(P02730)和组蛋白 H2A 类型 1(P0C0S8)组成的辅助诊断模型已经开发出来。混淆矩阵参数的结果表明,这种诊断方法在区分不确定的艾滋病毒感染病例方面具有很强的实用性:结论:通过蛋白质组学鉴定和预测的三个 DEPs 对艾滋病窗口期患者的补充鉴定非常有用。
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引用次数: 0
Point-of-care urine tenofovir test predicts future HIV preexposure prophylaxis discontinuation among young users. 护理点尿液替诺福韦检测可预测年轻使用者未来是否会停止使用艾滋病暴露前预防措施。
IF 3.4 2区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-20 DOI: 10.1097/QAD.0000000000003962
Tyler Martinson, Rikki Montoya, Carlos Moreira, Karen Kuncze, Kevin Sassaman, Megan J Heise, David V Glidden, K Rivet Amico, Emily A Arnold, Susan P Buchbinder, Leah Davis Ewart, Adam Carrico, Guohong Wang, Hideaki Okochi, Hyman M Scott, Monica Gandhi, Matthew A Spinelli

Background: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower preexposure prophylaxis (PrEP) adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS).

Methods: YMSM/TGW participants ( n  = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/ml) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days.

Results: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (<4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation [adjusted odds ratio (AOR) 6.1; 95% confidence interval (CI): 1.4-11; P  = 0.005] and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value.

Conclusions: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.

背景:年轻男男性行为者和变性女性(YMSM/TGW)的 HIV 感染率过高,而 PrEP 的依从性却较低。护理点(POC)尿液替诺福韦(TFV)快速检测(UTRA)允许在临床环境中对不依从性进行实时监测。我们在 PrEP 使用者中进行了 UTRA 检测,以研究 PrEP 依从性低与未来中止 PrEP 之间的关系,以及 POC 检测与黄金标准液相色谱串联质谱法(LC/MS/MS)相比的准确性:方法: YMSM/TGW 参与者(n = 100)是在日常 PrEP 访问中招募的。逻辑回归模型分析了尿液 POC 检测结果(临界值为 1,500 纳克/毫升)这一主要预测指标与 PrEP 中止这一主要结果之间的关系:总体而言,19%的参与者尿液TFV水平较低,21%的参与者中断了PrEP,而11%的参与者自我报告PrEP依从性较低(每周<4片),这对预测TFV水平较低的敏感性仅为43%,特异性为84%,且与PrEP中断无关。尿液中 TFV 含量低可预测 PrEP 的终止(AOR 6.1;95% CI:1.4-11;p = 0.005),对 120 天后的终止敏感度为 71%,特异度为 90%。与LC/MS/MS相比,UTRA检测的阳性预测值为98%,阴性预测值为100%:结论:在每天进行PrEP的YMSM/TGW样本中,POC UTRA检测比自我报告的依从性更准确地预测了PrEP的终止,与LC/MS/MS相比,预测值更高。UTRA检测可作为一种临床工具,用于指导那些尽管仍易感染艾滋病毒但却更有可能中止PrEP的人群采取预防性干预措施。
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引用次数: 0
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