Tali Wagner, Itzchak Levy, Anat Wieder-Finesod, Marina Wax, Yael Gozlan, Daniel Elbirt, Eynat Kedem, Karen Olshtain-Pops, Hila Elinav, Michal Chowers, Valery Istomin, Rozalia Smolyakov, Natasha Matus, Shirley Girshengorn, Rotem Marom, Dan Turner, Orna Mor
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A piecewise exponential additive mixed model was employed to estimate the association of various factors with aDRM.</p><p><strong>Results: </strong>Only 82 individuals had virological failure, 20/82 had multiple virological failures. The majority of virological failures (77%) were men, 48% were Israeli-born,79% were diagnosed in 2010-2014. Only 18% initiated with second-generation integrase-inhibitor (INI) based regimens. Although no baseline differences were identified between those with single and multiple virological failures, the latter had lower CD4 + levels before first virological failure. NRTI M184IV and INI N155H were identified in more than 10% of the cases. In those with additional failures, INI N155H was more prominent in cases with subtype B compared to those with non-B subtypes ( P = 0.039). Diagnoses with CD4 + cell count less than 200 cells/μl and AIDS [hazard ratio = 3.46, 95% confidence interval (95% CI): 1.51-7.92, P = 0.003], second-generation INI at the first virological failure (HR = 0.32, 95% CI: 0.11-0.91, P = 0.033), and RET at baseline (hazard ratio = 0.34, 95% CI: 0.13-0.86, P = 0.022) had a significant and persistent relative effect on aDRM.</p><p><strong>Conclusion: </strong>The risk for aDRM is reduced in those who are treated with second-generation INI-based regimens. Diagnosis with low CD4 + cell counts and AIDS is associated with detection of aDRM.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"760-765"},"PeriodicalIF":3.4000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Drug resistance testing at regimen failure in individuals diagnosed with HIV-1 between 2010 and 2018 in Israel.\",\"authors\":\"Tali Wagner, Itzchak Levy, Anat Wieder-Finesod, Marina Wax, Yael Gozlan, Daniel Elbirt, Eynat Kedem, Karen Olshtain-Pops, Hila Elinav, Michal Chowers, Valery Istomin, Rozalia Smolyakov, Natasha Matus, Shirley Girshengorn, Rotem Marom, Dan Turner, Orna Mor\",\"doi\":\"10.1097/QAD.0000000000004138\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Assess virological failures, analyze the results of resistance testing (RET), and investigate factors associated with acquired drug resistance mutations (aDRM).</p><p><strong>Design: </strong>A retrospective longitudinal cohort study.</p><p><strong>Methods: </strong>Virological failures (viral load >50 copies/ml) from a cohort of 1130 individuals, diagnosed with HIV-1 in 2010-2018 and followed up until 2020, were included. Demographic, clinical, and virological data were collected. A piecewise exponential additive mixed model was employed to estimate the association of various factors with aDRM.</p><p><strong>Results: </strong>Only 82 individuals had virological failure, 20/82 had multiple virological failures. The majority of virological failures (77%) were men, 48% were Israeli-born,79% were diagnosed in 2010-2014. Only 18% initiated with second-generation integrase-inhibitor (INI) based regimens. Although no baseline differences were identified between those with single and multiple virological failures, the latter had lower CD4 + levels before first virological failure. NRTI M184IV and INI N155H were identified in more than 10% of the cases. In those with additional failures, INI N155H was more prominent in cases with subtype B compared to those with non-B subtypes ( P = 0.039). Diagnoses with CD4 + cell count less than 200 cells/μl and AIDS [hazard ratio = 3.46, 95% confidence interval (95% CI): 1.51-7.92, P = 0.003], second-generation INI at the first virological failure (HR = 0.32, 95% CI: 0.11-0.91, P = 0.033), and RET at baseline (hazard ratio = 0.34, 95% CI: 0.13-0.86, P = 0.022) had a significant and persistent relative effect on aDRM.</p><p><strong>Conclusion: </strong>The risk for aDRM is reduced in those who are treated with second-generation INI-based regimens. Diagnosis with low CD4 + cell counts and AIDS is associated with detection of aDRM.</p>\",\"PeriodicalId\":7502,\"journal\":{\"name\":\"AIDS\",\"volume\":\" \",\"pages\":\"760-765\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"AIDS\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/QAD.0000000000004138\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"AIDS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QAD.0000000000004138","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/31 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：评估病毒学失败，分析耐药试验（RET）结果，探讨获得性耐药突变（aDRM）的相关因素。设计：回顾性纵向队列研究。方法：纳入2010-2018年诊断为HIV-1并随访至2020年的1130例患者的病毒学失败（病毒载量bbb50拷贝/ml）。收集了人口学、临床和病毒学数据。采用分段指数加性混合模型估计各因素与aDRM的相关性。结果：82例患者出现病毒学失败，20/82例患者出现多重病毒学失败。大多数病毒学失败（77%）是男性，48%是以色列出生的，79%是在2010-2014年被诊断出来的。只有18%的患者开始使用基于第二代整合酶抑制剂（INI）的方案。尽管在单次病毒学失败和多次病毒学失败之间没有发现基线差异，但后者在首次病毒学失败之前具有较低的CD4+水平。在超过10%的病例中发现了NRTI M184IV和INI N155H。在有其他失败的患者中，与非B亚型患者相比，INI N155H在B亚型患者中更为突出（P = 0.039）。诊断为CD4+细胞计数小于200个/μl和艾滋病[风险比= 3.46,95%可信区间（95% CI）： 1.51-7.92, P = 0.003]，第一次病毒学失败时的第二代INI （HR = 0.32, 95% CI: 0.11-0.91, P = 0.033）和基线时的RET（风险比= 0.34,95% CI: 0.13-0.86, P = 0.022）对aDRM有显著且持续的相对影响。结论：接受第二代以i为基础的方案治疗的患者发生aDRM的风险降低。CD4+细胞计数低和艾滋病的诊断与aDRM的检测有关。
Drug resistance testing at regimen failure in individuals diagnosed with HIV-1 between 2010 and 2018 in Israel.
Objective: Assess virological failures, analyze the results of resistance testing (RET), and investigate factors associated with acquired drug resistance mutations (aDRM).
Design: A retrospective longitudinal cohort study.
Methods: Virological failures (viral load >50 copies/ml) from a cohort of 1130 individuals, diagnosed with HIV-1 in 2010-2018 and followed up until 2020, were included. Demographic, clinical, and virological data were collected. A piecewise exponential additive mixed model was employed to estimate the association of various factors with aDRM.
Results: Only 82 individuals had virological failure, 20/82 had multiple virological failures. The majority of virological failures (77%) were men, 48% were Israeli-born,79% were diagnosed in 2010-2014. Only 18% initiated with second-generation integrase-inhibitor (INI) based regimens. Although no baseline differences were identified between those with single and multiple virological failures, the latter had lower CD4 + levels before first virological failure. NRTI M184IV and INI N155H were identified in more than 10% of the cases. In those with additional failures, INI N155H was more prominent in cases with subtype B compared to those with non-B subtypes ( P = 0.039). Diagnoses with CD4 + cell count less than 200 cells/μl and AIDS [hazard ratio = 3.46, 95% confidence interval (95% CI): 1.51-7.92, P = 0.003], second-generation INI at the first virological failure (HR = 0.32, 95% CI: 0.11-0.91, P = 0.033), and RET at baseline (hazard ratio = 0.34, 95% CI: 0.13-0.86, P = 0.022) had a significant and persistent relative effect on aDRM.
Conclusion: The risk for aDRM is reduced in those who are treated with second-generation INI-based regimens. Diagnosis with low CD4 + cell counts and AIDS is associated with detection of aDRM.
期刊介绍：
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