基于整合酶链转移抑制剂方案的紧急耐药性。

Emergent drug resistance with integrase strand transfer inhibitor-based regimens.

作者信息

Lepik Katherine J, Harrigan P Richard, Yip Benita, Wang Lu, Robbins Marjorie A, Zhang Wendy W, Toy Junine, Akagi Linda, Lima Viviane D, Guillemi Silvia, Montaner Julio S G, Barrios Rolando

机构信息

aBC Centre for Excellence in HIV/AIDS bPharmacy Department, St Paul's Hospital cFaculty of Medicine, Department of Medicine, Division of AIDS dFaculty of Medicine, School of Population and Public Health, University of BC, Vancouver, British Columbia, Canada.

出版信息

AIDS. 2017 Jun 19;31(10):1425-1434. doi: 10.1097/QAD.0000000000001494.

DOI:10.1097/QAD.0000000000001494

PMID:28375875

Abstract

OBJECTIVES

To estimate the incidence of and risk factors for emergent resistance to integrase strand transfer inhibitor (INSTI) and nucleoside(-tide) reverse transcriptase inhibitors (NRTI) in HIV-1-infected adults receiving an INSTI and two NRTIs.

DESIGN

Retrospective cohort study.

METHODS

Persons aged at least 19 years were included if they received their first prescription for raltegravir, elvitegravir or dolutegravir in British Columbia, Canada in 2012-2014 and were followed to 31 December 2015. Emergent resistance was defined as new mutations conferring intermediate-high level NRTI or INSTI resistance (score ≥30, Stanford HIV Drug Resistance Algorithm v.7.0.1). First-year resistance rates and 95% confidence intervals (95% CI) were estimated for 'any' (INSTI or NRTI) resistance using Poisson regression. The relationship between any emergent resistance and explanatory variables was modeled by Cox proportional hazards.

RESULTS

There were 270 raltegravir, 323 elvitegravir and 392 dolutegravir-treated persons who were predominantly male (77%), antiretroviral therapy (ART)-experienced (81%), with low prevalence of preexisting drug resistance (16%). INSTI and NRTI resistance emerged in both ART-experienced and ART-naive persons (including dolutegravir-treated ART-naive), with no statistically significant differences in 'any' resistance rates (95% CI) between INSTIs: raltegravir 3.80 (1.90, 7.60), elvitegravir 2.37 (1.06, 5.27) and dolutegravir 1.48 (0.62, 3.55)/100 person-years. The strongest factors associated with emergent resistance were CD4 less than 200 cells/μl, adjusted hazard ratio (95% CI) 10.46 (4.67, 23.41) and less than 80% adherence to the INSTI regimen hazard ratio 2.52 (1.11, 5.71).

CONCLUSION

Incident drug resistance rates were low with 'real-world' use of INSTI-based regimens. However, incomplete ART adherence and low CD4 cell count were associated with increased resistance rates regardless of which INSTI was prescribed. Provide adherence support and monitor for drug resistance.

摘要

目的

评估接受整合酶链转移抑制剂（INSTI）和两种核苷（酸）类逆转录酶抑制剂（NRTI）治疗的HIV-1感染成人中出现对INSTI和NRTI紧急耐药的发生率及危险因素。

设计

回顾性队列研究。

方法

纳入年龄至少19岁、于2012年至2014年在加拿大不列颠哥伦比亚省首次开具拉替拉韦、埃替拉韦或多替拉韦处方并随访至2015年12月31日的患者。紧急耐药定义为出现赋予中高水平NRTI或INSTI耐药的新突变（评分≥30，斯坦福HIV耐药算法v.7.0.1）。使用泊松回归估计“任何”（INSTI或NRTI）耐药的第一年耐药率及95%置信区间（95%CI）。通过Cox比例风险模型对任何紧急耐药与解释变量之间的关系进行建模。

结果

有270例接受拉替拉韦治疗、323例接受埃替拉韦治疗和392例接受多替拉韦治疗的患者，主要为男性（77%），有抗逆转录病毒治疗（ART）经验（81%），既往耐药患病率较低（16%）。在有ART经验和无ART经验的患者中（包括接受多替拉韦治疗的无ART经验患者）均出现了INSTI和NRTI耐药，不同INSTI之间“任何”耐药率（95%CI）无统计学显著差异：拉替拉韦为3.80（1.90，7.60）/100人年，埃替拉韦为2.37（1.06，5.27）/100人年，多替拉韦为1.48（0.62，3.55）/100人年。与紧急耐药相关的最强因素是CD4细胞计数低于200个/μl，调整后风险比（95%CI）为10.46（4.67，23.41），以及对INSTI方案的依从性低于80%，风险比为2.52（1.11，5.71）。