达芦那韦/利托那韦联合拉替拉韦治疗初治 HIV-1 感染患者的疗效（ACTG A5262）。
Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262).
机构信息
Division of Infectious Diseases, Northwestern University, Chicago, Illinois 60611, USA.
出版信息
AIDS. 2011 Nov 13;25(17):2113-22. doi: 10.1097/QAD.0b013e32834bbaa9.
OBJECTIVE
To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL) combination therapy in antiretroviral-naive patients.
DESIGN
Phase IIb, single-arm, open-label, multicenter study.
METHODS
One hundred and twelve antiretroviral-naive, HIV-1-infected patients received DRV/r 800/100 mg once daily and RAL 400 mg twice daily. Primary endpoint was virologic failure by week 24. Virologic failure was defined as confirmed viral load of 1000 copies/ml or more at week 12, or an increase of more than 0.5 log(10) copies/ml in viral load from week 4 to 12, or a confirmed viral load of more than 50 copies/ml at or after week 24. Protease and integrase genes were sequenced in patients experiencing virologic failure.
RESULTS
Virologic failure rate was 16% [95% confidence interval (CI) 10-24] by week 24 and 26% (95% CI 19-36) by week 48 in an intent-to-treat analysis. Viral load at virologic failure was 51-200 copies/ml in 17/28 failures. Adjusting for age and sex, virologic failure was associated with baseline viral load of more than 100,000 copies/ml [hazard ratio 3.76, 95% CI (1.52-9.31), P = 0.004] and lower CD4 cell count [0.77 per 100 cells/μl increase (95% CI 0.61-0.98), P = 0.037]. When trough RAL concentrations were included as a time-varying covariate in the analysis, virologic failure remained associated with baseline viral load more than 100,000 copies/ml [hazard ratio = 4.67 (95% CI 1.93-11.25), P < 0.001], whereas RAL level below detection limit in plasma at one or more previous visits was associated with increased hazard [hazard ratio = 3.42 (95% CI 1.41-8.26), P = 0.006]. All five participants with integrase mutations during virologic failure had baseline viral load more than 100,000 copies/ml.
CONCLUSION
DRV/r plus RAL was effective and well tolerated in most patients, but virologic failure and integrase resistance were common, particularly in patients with baseline viral load more than 100,000 copies/ml.
目的
探索达芦那韦/利托那韦（DRV/r）加雷特格韦（RAL）联合治疗初治患者。
设计
IIb 期、单臂、开放性、多中心研究。
方法
112 例初治、HIV-1 感染的患者接受每日一次 DRV/r 800/100mg 和每日两次 RAL 400mg。主要终点为第 24 周的病毒学失败。病毒学失败定义为第 12 周时确认病毒载量超过 1000 拷贝/ml，或第 4 周至 12 周期间病毒载量增加超过 0.5log10 拷贝/ml，或第 24 周或之后时确认病毒载量超过 50 拷贝/ml。对出现病毒学失败的患者进行蛋白酶和整合酶基因测序。
结果
意向治疗分析中，第 24 周时病毒学失败率为 16%（95%CI 10-24），第 48 周时为 26%（95%CI 19-36）。28 例失败中有 17 例病毒学失败时病毒载量为 51-200 拷贝/ml。调整年龄和性别后，病毒学失败与基线时病毒载量超过 100,000 拷贝/ml相关[风险比 3.76，95%CI（1.52-9.31），P=0.004]，与 CD4 细胞计数较低相关[每增加 100 个细胞/μl 增加 0.77（95%CI 0.61-0.98），P=0.037]。当将谷浓度 RAL 作为分析中的时变协变量时，病毒学失败仍然与基线时病毒载量超过 100,000 拷贝/ml相关[风险比=4.67（95%CI 1.93-11.25），P<0.001]，而在一次或多次先前就诊时血浆中 RAL 浓度低于检测下限与增加的风险相关[风险比=3.42（95%CI 1.41-8.26），P=0.006]。在病毒学失败期间出现整合酶突变的所有 5 名患者基线时病毒载量均超过 100,000 拷贝/ml。
结论
DRV/r 加 RAL 对大多数患者有效且耐受性良好，但病毒学失败和整合酶耐药较为常见，特别是基线时病毒载量超过 100,000 拷贝/ml的患者。
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