sHIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies.
sHIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies.
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接受基于多替拉韦的 ART 人群中 sHIV-1 耐药性：队列研究的协作分析。
DOI：
10.1101/2023.04.05.23288183
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Günthard,Huldry
中科院分区：
文献类型：
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作者：
Loosli,Tom;Hossmann,Stefanie;Ingle,SuzanneM;Okhai,Hajra;Kusejko,Katharina;Mouton,Johannes;Bellecave,Pantxika;vanSighem,Ard;Stecher,Melanie;d'ArminioMonforte,Antonella;Gill,MJohn;Sabin,CarolineA;Maartens,Gary;Günthard,Huldry
背景资料：在一线和二线抗逆转录病毒治疗（ART）中广泛使用整合酶链转移抑制剂（DITI）度鲁特韦（DTG）可能会促进出现耐药性。我们结合了来自HIV队列的数据，以检查耐药突变（DRM）的模式，并确定DTG耐药的风险因素。研究方法：来自加拿大、欧洲和南非的8个队列提供了对基于DTG的ART进行基因型耐药检测的个体数据。使用斯坦福大学算法对耐药水平进行分类。我们使用混合效应有序逻辑回归模型确定了耐药的危险因素。结果：我们纳入了2013年至2022年期间对基于DTG的ART进行基因型耐药检测的750人。大多数患者患有HIV亚型B（N=444，59·2%），并且有治疗经验; 134例（17·9%）接受DTG双重治疗，19例（2·5%）接受DTG单药治疗。在100例（13.3%）个体中检测到了CIMI DRMs; 21例（2.8%）有一个以上的突变。713株（95.1%）对DTG敏感，8株（1.1%）为低抗，5株（0.7%）为低抗，18株（2.4%）为中抗，6株（0.8%）为高抗。DTG单药治疗的DTG耐药风险较高（校正比值比（aOR）37·25，95% CI 11·17至124·2）和DTG拉米夫定双重治疗（aOR 6.59，95% CI 1.70至25.55），在潜在低/低剂量情况下更高（aOR 4.62，95%CI 1.24至17.2）或中/高水平（aOR 7.01，95%CI 2.52至19.48）核苷逆转录酶抑制剂（NRTI）耐药。DTG上的病毒载量显示DTG耐药性增加的趋势（aOR 1.42，95% CI 0.92至2.19，根据log 10病毒载量曲线下面积的标准差）。解释：在基于DTG的ART病毒学失败的人群中，CDFI DRMs不常见，DTG耐药罕见。DTG单药治疗和NRTI耐药大大增加了DTG耐药的风险，这是一个值得关注的问题，特别是在资源有限的环境中。
Background: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) in first- and second-line antiretroviral therapy (ART) may facilitate emerging resistance. We combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for DTG resistance. Methods: Eight cohorts from Canada, Europe, and South Africa contributed data on individuals with genotypic resistance testing on DTG-based ART. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. Results: We included 750 people with genotypic resistance testing on DTG-based ART between 2013 and 2022. Most had HIV subtype B (N=444, 59·2%) and were treatment-experienced; 134 (17.9%) were on DTG dual and 19 (2.5%) on DTG monotherapy. INSTI DRMs were detected in 100 (13·3%) individuals; 21 (2·8%) had more than one mutation. Most (N=713, 95·1%) were susceptible to DTG, 8 (1·1%) had potential-low, 5 (0·7%) low, 18 (2·4%) intermediate and 6 (0·8%) high-level DTG resistance. The risk of DTG resistance was higher on DTG monotherapy (adjusted odds ratio (aOR) 37·25, 95% CI 11·17 to 124·2) and DTG lamivudine dual therapy (aOR 6·59, 95% CI 1·70 to 25·55) compared to combination ART, and higher in the presence of potential-low/low (aOR 4.62, 95% CI 1.24 to 17.2) or intermediate/high-level (aOR 7·01, 95% CI 2·52 to 19·48) nucleoside reverse transcriptase inhibitors (NRTI) resistance. Viral load on DTG showed a trend towards increased DTG resistance (aOR 1·42, 95% CI 0·92 to 2·19 per standard deviation of log10 area under the viral load curve). Interpretation: Among people experiencing virological failure on DTG-based ART, INSTI DRMs were uncommon, and DTG resistance was rare. DTG monotherapy and NRTI resistance substantially increased the risk for DTG resistance, which is of concern, notably in resource-limited settings.