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A Randomized, Double-blind, Placebo-controlled, Short-term Monotherapy Study of MK-6186, an HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), in Treatment-Naïve HIV-Infected Participants. 一项针对HIV-1非核苷类逆转录酶抑制剂(NNRTI)的随机、双盲、安慰剂对照短期单一疗法研究。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-18 DOI: 10.1089/aid.2023.0152
Dirk Schürmann,Andreas Hueser,Frieder Pfaefflin,Caroline Cilissen,Inge de Lepeleire,Patrick Larson,Matt Anderson,Matthew Rizk,Joerg Hofmann,Martin Daeumer,Miriam Stegemann,Selwyn Aubrey Stoch,Frank Wagner,Marian Iwamoto
{"title":"A Randomized, Double-blind, Placebo-controlled, Short-term Monotherapy Study of MK-6186, an HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), in Treatment-Naïve HIV-Infected Participants.","authors":"Dirk Schürmann,Andreas Hueser,Frieder Pfaefflin,Caroline Cilissen,Inge de Lepeleire,Patrick Larson,Matt Anderson,Matthew Rizk,Joerg Hofmann,Martin Daeumer,Miriam Stegemann,Selwyn Aubrey Stoch,Frank Wagner,Marian Iwamoto","doi":"10.1089/aid.2023.0152","DOIUrl":"https://doi.org/10.1089/aid.2023.0152","url":null,"abstract":"OBJECTIVETo assess the antiviral activity, pharmacokinetics, and safety of MK-6186 in NNRTI-naïve, HIV-1-infected male participants.DESIGNDouble-blind, randomized, two-panel study.METHODSIn 2 sequential panels, 18 participants received MK-6186 (40 mg [Panel A] or 150 mg [Panel B]) or matching placebo once daily for 7 days. Plasma samples were collected for measurement of HIV-1 RNA levels and MK-6186 pharmacokinetics.RESULTSFor the mean change from baseline in HIV-1 RNA (log10 copies/mL) at 24 hours post Day 7 dose, the mean difference (90% confidence interval) between MK-6186 and placebo was 1.54 (-1.73, -1.34) in the 40-mg group and -1.28 (-1.81, -0.75) in the 150-mg group. One participant in the 150-mg group had viral rebound at 24 hours after Day 6 dosing (Day 7 predose) associated with outgrowth of the V106A minority variant. Ultra-deep sequencing confirmed expansion of this predose minority variant from 0.26% to 63.67%. No outgrowth and rebound was seen in another participant in whom a V106A minority variant was also detected. MK-6186 was generally well tolerated. MK-6186 was rapidly absorbed with peak concentrations at 2 hours followed by a biphasic decline. The effective t½ of MK-6186 was 43.9 to 48.7 hrs. Steady state was not achieved.CONCLUSIONSDaily monotherapy with MK-6186 demonstrated robust antiviral activity with maximal antiviral activity at a dose of 40 mg. One participant in the 150-mg group exhibited viral rebound with outgrowth of the resistant V106A minority variant, demonstrating a risk of resistance development typical of NNRTIs. The reason for this outgrowth remains unclear as no outgrowth occurred in a participant in the 40-mg group in whom the V106A minority variant was also detected. MK-6186 may be an alternative next-generation NNRTI in combination therapy, in that combination antiretroviral therapy could prevent outgrowth of resistant minority variants.","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
CD57+ T cell transmigration through vascular endothelial cells is enhanced by TNF: A novel model of cardiovascular risk in people with HIV. TNF 可增强 CD57+ T 细胞通过血管内皮细胞的迁移:艾滋病病毒感染者心血管风险的新模型。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-18 DOI: 10.1089/aid.2024.0057
Xi Su,Michael Freeman
{"title":"CD57+ T cell transmigration through vascular endothelial cells is enhanced by TNF: A novel model of cardiovascular risk in people with HIV.","authors":"Xi Su,Michael Freeman","doi":"10.1089/aid.2024.0057","DOIUrl":"https://doi.org/10.1089/aid.2024.0057","url":null,"abstract":"People with human immunodeficiency virus (PWH), despite achieving viral suppression through antiretroviral therapy, face increased risk and earlier onset of atherosclerotic cardiovascular diseases than the general population. CD57+ T cells can be readily recovered from atherosclerotic plaques and likely contribute to disease by targeting endothelial cells (ECs), however the specific mechanisms facilitating the infiltration of these cells into plaques remain elusive. Here, we report the development of a novel assay to quantify T cell adhesion to and transmigration through a primary human vascular EC monolayer and show that CD57+ T cells preferentially adhere to and transmigrate through the monolayer. Moreover, activating the ECs with tumor necrosis factor (TNF) significantly increased the transmigration of CD57+ T cells, supporting a role for TNF in promoting the vascular homing of CD57+ T cells. This model will allow for elucidating the mechanisms of, and testing interventions to prevent, CD57+ T cell infiltration into plaques.","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
An Integrated DAIDS Laboratory Oversight Framework: Application of the DAIDS GCLP Guidelines. DAIDS 实验室综合监督框架:DAIDS GCLP 指南的应用。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-04 DOI: 10.1089/AID.2024.0041
Naana Cleland, Nina Kunwar, Usha Sharma, Jamal Dejli, Milton Maciel, Daniella Livnat, Judith Miller, Keith Crawford, Fatima Jones, M Patricia D'Souza
{"title":"An Integrated DAIDS Laboratory Oversight Framework: Application of the DAIDS GCLP Guidelines.","authors":"Naana Cleland, Nina Kunwar, Usha Sharma, Jamal Dejli, Milton Maciel, Daniella Livnat, Judith Miller, Keith Crawford, Fatima Jones, M Patricia D'Souza","doi":"10.1089/AID.2024.0041","DOIUrl":"10.1089/AID.2024.0041","url":null,"abstract":"<p><p>The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, and validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training, encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Strengthening the Application of the DAIDS GCLP Guidelines: The Implementation of an Integrated Laboratory Oversight Framework. 加强 DAIDS GCLP 准则的应用:实施综合实验室监督框架。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-04 DOI: 10.1089/AID.2024.0042
Loc Nguyen, Anne Leach, Estelle Piwowar-Manning, Mark Marzinke, Allan Levesque, Claudine Gregorio, Kristen Skinner, Tiri Towindo, Heidi Hanes, Kwabena Sarpong, Christian Kasongo, Natasha Samsunder, Grace Aldrovandi, Kathie G Ferbas, Andries Engelbrecht, Michael Stirewalt, Emily Anyango, Sasiwimol Ubolyam, Pamela Lankford-Turner, Marcella Sarzotti-Kelsoe
{"title":"Strengthening the Application of the DAIDS GCLP Guidelines: The Implementation of an Integrated Laboratory Oversight Framework.","authors":"Loc Nguyen, Anne Leach, Estelle Piwowar-Manning, Mark Marzinke, Allan Levesque, Claudine Gregorio, Kristen Skinner, Tiri Towindo, Heidi Hanes, Kwabena Sarpong, Christian Kasongo, Natasha Samsunder, Grace Aldrovandi, Kathie G Ferbas, Andries Engelbrecht, Michael Stirewalt, Emily Anyango, Sasiwimol Ubolyam, Pamela Lankford-Turner, Marcella Sarzotti-Kelsoe","doi":"10.1089/AID.2024.0042","DOIUrl":"10.1089/AID.2024.0042","url":null,"abstract":"<p><p>The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, validity, and safety of the clinical research or trial participants and laboratory staff and ensures adherence to regulatory requirements. Acknowledgment and adoption of the DAIDS GCLP Guidelines are critical in building laboratory capacity and preparedness for conducting clinical trials. In collaboration with DAIDS, laboratory experts support the implementation of the DAIDS Integrated Laboratory Oversight Framework (Framework) activities. This article describes the implementation of the GCLP Guidelines, the Framework activities, and the coordinated efforts to strengthen laboratory performance. The Framework activities include four components: Quality Assurance Oversight, GCLP Audits, GCLP Training, and Laboratory Quality Improvement. Comparison of GCLP Guidelines with other regulations or standards, including U.S. Clinical Laboratory Improvement Amendments regulation 42 CFR 493, College of American Pathologists, World Health Organization GCLP, and International Organization for Standardization, ISO 15189:2012 standards, highlighted the differences and similarities to guide integration and harmonization efforts. Processes related to the Framework activities are outlined in detail, including key data derived from the managed activities of over 175 laboratories worldwide. Via the evolution of the DAIDS GCLP Guidelines and laboratory oversight workflows, the laboratories participating in DAIDS-sponsored clinical research and trials have successfully participated in internal and external regulatory audits. The collaborative and integrated oversight approach promotes knowledge-sharing and accountability to support the implementation of the DAIDS GCLP Guidelines and compliance monitoring. Lessons learned have helped with the implementation of the DAIDS integrated laboratory oversight approach and quality oversight programs at multiple laboratories worldwide.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Nonnegligible Contribution of Nonlymphoid Tissue to Viral Reservoir During the Short-Term Early cART in SIVmac239-Infected Chinese Rhesus Macaques. 在SIVmac239感染的中国猕猴的短期早期cART期间,非淋巴组织对病毒库的贡献不可忽略。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-01 Epub Date: 2024-04-12 DOI: 10.1089/AID.2023.0130
Ren-Rong Tian, Ting Li, Ming-Xu Zhang, Tian-Zhang Song, Hong-Yi Zheng, Yong-Tang Zheng
{"title":"Nonnegligible Contribution of Nonlymphoid Tissue to Viral Reservoir During the Short-Term Early cART in SIVmac239-Infected Chinese Rhesus Macaques.","authors":"Ren-Rong Tian, Ting Li, Ming-Xu Zhang, Tian-Zhang Song, Hong-Yi Zheng, Yong-Tang Zheng","doi":"10.1089/AID.2023.0130","DOIUrl":"10.1089/AID.2023.0130","url":null,"abstract":"<p><p>HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate <i>de novo</i> infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Exploring HIV-1 Transmission Features Among Older Individuals in Developed Eastern China. 探索中国东部发达地区老年人的 HIV-1 传播特征。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-01 Epub Date: 2024-03-14 DOI: 10.1089/AID.2023.0066
Ke Xu, Junfang Chen, Min Zhu, Xingliang Zhang, Sisheng Wu, Wenjie Luo, Ling Ye
{"title":"Exploring HIV-1 Transmission Features Among Older Individuals in Developed Eastern China.","authors":"Ke Xu, Junfang Chen, Min Zhu, Xingliang Zhang, Sisheng Wu, Wenjie Luo, Ling Ye","doi":"10.1089/AID.2023.0066","DOIUrl":"10.1089/AID.2023.0066","url":null,"abstract":"<p><p>The number of newly reported HIV-1 infections among older individuals (≥50 years of age) has increased rapidly in Hangzhou, a central city in the Yangtze River Delta region of China. To provide a scientific basis for prevention and intervention strategies targeted at older individuals in Hangzhou, an epidemiological survey combined with molecular transmission network analysis was conducted. A total of 2,899 individuals with newly confirmed HIV-1 infections, including 635 older individuals and 2,264 younger individuals (<50 years of age), were enrolled in this study. Among older individuals, heterosexual contact was the predominant mode of HIV-1 transmission. In addition, it was observed that older individuals with lower levels of education exhibited a higher susceptibility to HIV-1 infection. The analysis of transmission network, which was inferred using HIV-TRACE algorithm, revealed that the newly diagnosed HIV-1 infections among older individuals in Hangzhou exhibited a pattern of scattered transmission, with key clusters primarily located in non-main urban areas. The predominant mode of transmission in these areas was nonmarital and noncommercial or nonmarital and commercial heterosexual transmission. Notably, the study highlighted a significant proportion of older individuals (73.3%, 11/15) within B subtype. Multivariate logistic regression analysis further revealed that the subtype B was a significant factor associated with older individuals having ≥3 node degrees in the network, occurring 5.55 times more frequent than subtype CRF07_BC (95% confidence intervals = 1.17-26.22, <i>p</i> = .031). Furthermore, the lower CD4 levels observed among older individuals underscored the challenge of late diagnosis in Hangzhou. Taken together, it is imperative to test and intervene for high-risk older individuals. To tackle this issue effectively, it is essential to enhance the detection of the B subtype and implement targeted interventions in key clusters within non-main urban areas. In addition, proactive measures should be implemented to address the challenge of late diagnosis in Hangzhou by promoting widespread testing among the older individuals, particularly in priority areas.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for AIDS Research and Human Retroviruses. 罗莎琳德-富兰克林学会自豪地宣布 2023 年艾滋病研究和人类逆转录病毒奖获得者。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-01 DOI: 10.1089/aid.2024.17445.rfs2023
Sharon Walmsley
{"title":"Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for <i>AIDS Research and Human Retroviruses</i>.","authors":"Sharon Walmsley","doi":"10.1089/aid.2024.17445.rfs2023","DOIUrl":"https://doi.org/10.1089/aid.2024.17445.rfs2023","url":null,"abstract":"","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis. 与 SIV 相关的心脏病变或脑炎相比,Galectin-3、galectin-9 和 IL-18 与单核细胞活化和周转的关系更为密切。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-01 Epub Date: 2024-06-12 DOI: 10.1089/AID.2024.0008
Andrew K Ding, Zoey K Wallis, Kevin S White, Cinar Efe Sumer, Woong-Ki Kim, Amir Ardeshir, Kenneth C Williams
{"title":"Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis.","authors":"Andrew K Ding, Zoey K Wallis, Kevin S White, Cinar Efe Sumer, Woong-Ki Kim, Amir Ardeshir, Kenneth C Williams","doi":"10.1089/AID.2024.0008","DOIUrl":"10.1089/AID.2024.0008","url":null,"abstract":"<p><p>Despite antiretroviral therapy (ART), people living with HIV (PLWH) are at increased risk of developing cardiovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND), among other comorbidities. Studies from ART-treated individuals identified galectin-3 (gal-3) and interleukin (IL)-18 as CVD biomarkers, galectin-9 (gal-9) as a HAND biomarker, and sCD163, a marker of monocyte/macrophage activation, as a biomarker of both. We asked if plasma gal-3, gal-9, and IL-18 are associated with an individual comorbidity or increase in both with animals that develop AIDS with both pathologies versus (CVD-path) alone or simian immunodeficiency virus encephalitis (SIVE) alone. We found that no biomarkers were selective between individual pathologies, and all biomarkers increased with co-development of CVD-path and SIVE (gal-3, <i>p</i> = 0.11; gal-9, <i>p</i> = 0.001; IL-18, <i>p</i> = 0.007; sCD163, <i>p</i> < 0.001; %BrdU <i>p</i> = 0.02). Although gal-3, gal-9, and IL-18 did not distinguish between pathologies, they correlated strongly with one another, with sCD163, a marker of monocyte/macrophage activation, and the %BrdU monocytes, a marker of monocyte turnover. Compared to animals with CVD-path or SIVE alone, animals that co-developed both pathologies had consistently elevated IL-18 throughout infection (<i>p</i> = 0.02) and increased sCD163 in late infection (<i>p</i> = 0.01). These data indicate that gal-3, gal-9, and IL-18 are associated with monocyte/macrophage activation by sCD163 and monocyte turnover by the %BrdU+ monocytes more so than CVD-path or SIVE.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Antiretroviral Therapy Suppresses RNA N6-Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals. 抗逆转录病毒疗法可抑制 HIV-1 感染者外周血单核细胞中的 RNA N6-甲基腺苷修饰。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-01 Epub Date: 2024-05-23 DOI: 10.1089/AID.2024.0003
Tarun Mishra, Stacia Phillips, Crystal Maldonado, Jack T Stapleton, Li Wu
{"title":"Antiretroviral Therapy Suppresses RNA <i>N</i><sup>6</sup>-Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals.","authors":"Tarun Mishra, Stacia Phillips, Crystal Maldonado, Jack T Stapleton, Li Wu","doi":"10.1089/AID.2024.0003","DOIUrl":"10.1089/AID.2024.0003","url":null,"abstract":"<p><p>RNA <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification is important for regulating gene expression and innate immune responses to viral infection. HIV-1 <i>in vitro</i> infection induces a significant increase in m<sup>6</sup>A modification of cellular RNA; however, whether m<sup>6</sup>A levels of cellular RNA are affected by HIV-1 replication or by antiretroviral therapy (ART) in infected individuals remains unknown. Using dot blot or enzyme-linked immunosorbent assay, we measured RNA m<sup>6</sup>A levels of peripheral blood mononuclear cells (PBMCs) from healthy donors or HIV-1-infected individuals with or without ART. Using a reverse transcription-quantitative polymerase chain reaction array, we quantified expression levels of 84 type-I interferon (IFN-I)-responsive genes in PBMCs from some individuals of these three groups. RNA m<sup>6</sup>A levels in PBMCs from HIV-1 viremic patients (<i>n</i> = 10) were significantly higher (<i>p</i> ≤ .0001) compared with ART-treated individuals (<i>n</i> = 22) or 1.5-fold higher compared with healthy donors (<i>n</i> = 14). However, the increase in RNA m<sup>6</sup>A levels did not correlate with changes in the expression of 10 m<sup>6</sup>A-regulatory genes. We found significant upregulation and downregulation in the expression of several IFN-I-responsive genes from HIV-1 viremic patients (<i>n</i> = 4) and ART-treated patients (<i>n</i> = 6) compared with healthy donors (<i>n</i> = 5), respectively. Our results suggest that post-transcriptional m<sup>6</sup>A modification may contribute to the regulation of IFN-I-responsive gene expression during HIV-1 infection and ART.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Evaluation of Urinary Free Light Chains as a Marker of Severity of HIV Disease and Its Correlation with CD4 Count: A Pilot Study. 评估尿游离轻链作为 HIV 疾病严重程度的标志物及其与 CD4 细胞计数的相关性:试点研究。
IF 1.5 4区 医学
AIDS research and human retroviruses Pub Date : 2024-09-01 Epub Date: 2024-06-18 DOI: 10.1089/AID.2023.0100
Dhananjaya Melkunte Shanthaiah, Anubhuti Chitkara, Srinivasa Murthy, Dinesh Srivastava
{"title":"Evaluation of Urinary Free Light Chains as a Marker of Severity of HIV Disease and Its Correlation with CD4 Count: A Pilot Study.","authors":"Dhananjaya Melkunte Shanthaiah, Anubhuti Chitkara, Srinivasa Murthy, Dinesh Srivastava","doi":"10.1089/AID.2023.0100","DOIUrl":"10.1089/AID.2023.0100","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) infection weakens immunity. Monitoring the immune status of the patient has become an important aspect of evaluating the progression of the disease and informing follow-up after treatment. Estimation of CD4 counts is quite costly and requires expertise in flow cytometry. In certain pathologies, free light chains (FLCs) are secreted in serum and urine and the magnitude can be used to monitor the severity, progression, and therapeutic monitoring of the disease. Urine as a specimen proves cost-effective and presents reduced risks during sample collection. The stability of light chains in urine at room temperature over extended periods simplifies the management of sample transportation as well. Hence, a pilot cross-sectional study was planned to evaluate the levels of urinary immunoglobulins in patients with HIV. The study was conducted at PGIMER, Dr. Ram Manohar Lohia Hospital (presently ABVIMS), New Delhi. Sixty-nine consecutive ART-naive HIV patients aged between 18 and 40 years and 69 age- and sex-matched healthy controls were included in the study. Urinary FLC kappa (κ) and lambda (λ) were measured using an immunoglobulin ELISA kit. Baseline urinary κ light chain levels were significantly higher in cases when compared with controls (<i>p</i> < .001) and were found to be increased with increasing WHO immunological classes (<i>p</i> < .001) and inversely related to CD4 cell count. However, no significant difference in mean urinary λ immunoglobulin light chain between cases and controls was found and no correlation with CD4 cell count or with stages of WHO immunological classification of HIV disease was observed. It is suggested that urinary free κ chain measurements combined with serum light chain measurements may be a useful marker in the follow-up and monitoring of response to therapies in patients with HIV where testing by flow cytometry is not available.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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