在临床环境中，整合酶抑制剂在治疗经验丰富的患者中的疗效。
Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting.
机构信息
Department of Medicine.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
出版信息
AIDS. 2019 Jun 1;33(7):1187-1195. doi: 10.1097/QAD.0000000000002194.
OBJECTIVE
Characterize virologic and immunologic outcomes of INSTI-based antiretroviral therapy (ART) in experienced patients with and without virologic failure.
DESIGN
Prospective clinical cohort.
METHODS
ART-experienced, INSTI-naive participants in the University of North Carolina Center for AIDS Research HIV Clinical Cohort (UCHCC) initiating an INSTI-containing regimen 2007-2016 were followed from INSTI initiation (baseline) to the earliest of: outcome of interest, loss to follow-up (LTFU, 1 year without clinical visit), or death. Outcomes of interest were virologic failure (first of two consecutive viral loads at least 200 copies/ml more than 2 weeks apart, or one viral load ≥200 before LTFU) and immune recovery (first CD4 ≥500 cells/μl). Patients with baseline viral load at least 50 copies/ml were given 24 weeks before meeting virologic failure criteria. Kaplan-Meier curves and Cox proportional hazards models compared INSTI regimens and patient characteristics.
RESULTS
Of 773 patients, 32% were women, 59% African-American, and 42% had a viral load at least 50 copies/ml at INSTI initiation. After 2 years, 5% of patients with baseline viral load less than 50 copies/ml experienced virologic failure, compared with 35% of patients with baseline viral load at least 50 copies/ml (P < 0.01). Among patients with baseline viral load less than 50 copies/ml, dolutegravir/NRTIs was associated with longer time to virologic failure [adjusted hazard ratio (aHR) 0.11, 95% confidence interval (CI) 0.01-0.80], whereas among patients with baseline viral load at least 50 copies/ml, raltegravir/NRTIs was associated with longer time to virologic failure (aHR 0.35, 95% CI 0.18-0.68), both compared with elvitegravir/NRTIs. After 5 years suppressed, irrespective of baseline viral load, 61% of patients experienced immune recovery.
CONCLUSION
In this cohort, INSTI-containing regimens led to low virologic failure rates in patients switching ART while suppressed. Viremic patients initiating INSTIs were at high risk of virologic failure during follow-up.
目的
描述经验丰富的患者在病毒学和免疫方面的结果，这些患者接受 INSTI 为基础的抗逆转录病毒治疗（ART），并经历了病毒学失败和未经历病毒学失败。
设计
前瞻性临床队列研究。
方法
2007 年至 2016 年，UNC 艾滋病研究 HIV 临床队列（UCHCC）中接受过 ART 治疗且未使用 INSTI 的参与者开始使用包含 INSTI 的方案，从 INSTI 开始（基线）到出现以下最早情况之一：感兴趣的结果、失访（LTFU，1 年内无临床就诊）或死亡。感兴趣的结果是病毒学失败（两次连续病毒载量至少相差 200 拷贝/ml 以上的首次，或 LTFU 前一次病毒载量≥200 拷贝/ml）和免疫恢复（首次 CD4 细胞≥500 个/μl）。基线病毒载量至少为 50 拷贝/ml 的患者在达到病毒学失败标准前给予 24 周的治疗。Kaplan-Meier 曲线和 Cox 比例风险模型比较了 INSTI 方案和患者特征。
结果
在 773 名患者中，32%为女性，59%为非裔美国人，42%在开始使用 INSTI 时病毒载量至少为 50 拷贝/ml。2 年后，基线病毒载量低于 50 拷贝/ml 的患者中，5%发生病毒学失败，而基线病毒载量至少为 50 拷贝/ml 的患者中，35%发生病毒学失败（P<0.01）。在基线病毒载量低于 50 拷贝/ml 的患者中，多替拉韦/ NRTIs 与病毒学失败的时间延长相关（调整后的危险比[aHR]为 0.11，95%置信区间[CI]为 0.01-0.80），而在基线病毒载量至少为 50 拷贝/ml 的患者中，raltegravir/NRTIs 与病毒学失败的时间延长相关（aHR 为 0.35，95%CI 为 0.18-0.68），这两种情况均与elvitegravir/NRTIs 相比。5 年后，无论基线病毒载量如何，61%的患者出现免疫恢复。
结论
在本队列中，接受抑制性 ART 治疗的患者在转换为 INSTI 时，病毒学失败率较低。在开始使用 INSTI 时病毒载量较高的患者在随访期间发生病毒学失败的风险较高。
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