Demarest James, Underwood Mark, St Clair Marty, Dorey David, Brown Dannae, Zolopa Andrew
1 ViiV Healthcare , Research Triangle Park, North Carolina.
2 GlaxoSmithKline , Mississauga, Ontario, Canada .
AIDS Res Hum Retroviruses. 2018 Apr;34(4):343-346. doi: 10.1089/AID.2017.0184. Epub 2018 Mar 22.
In the SAILING study, dolutegravir demonstrated superior virologic efficacy compared with raltegravir in treatment-experienced, integrase strand transfer inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to ≥2 antiretroviral drug classes. Significantly fewer dolutegravir-treated patients demonstrated virologic failure with treatment-emergent resistance than raltegravir-treated patients through 48 weeks. Investigator-selected background therapy (ISBT) included at least one fully active agent, selected on the basis of resistance analysis. Genotypic and phenotypic resistance testing were performed on baseline and time-of-failure samples from patients with protocol-defined virologic failure (PDVF). A post hoc analysis of SAILING (N = 715; 354 dolutegravir, 361 raltegravir) assessed efficacy in subpopulations defined by ISBT activity, resistance profiles, and treatment history. When ISBT contained only nucleoside reverse transcriptase inhibitors (NRTIs), PDVF occurred in 0% (0/32) of dolutegravir-treated patients and 21.9% (7/32) of raltegravir-treated patients (p = .005). In patients harboring M184 V whose ISBT contained lamivudine or emtricitabine plus a second NRTI, 0% (0/13) of dolutegravir- and 33.3% (4/12) of raltegravir-treated patients (p = .026) experienced PDVF. Among patients receiving protease inhibitor (PI)-containing ISBT, 6.0% (18/300) of dolutegravir-treated patients versus 11.8% (36/305) of raltegravir-treated patients (p = .012) experienced PDVF. Darunavir/ritonavir was part of ISBT in 130 dolutegravir-treated patients and 145 raltegravir-treated patients; 6 (4.6%) and 12 (8.3%), respectively, experienced PDVF (difference -3.7%; 95% confidence interval: -10.1% to 2.5%; p = .256). There was no or less virologic failure in treatment-experienced, INSTI-naive subjects receiving dolutegravir versus raltegravir, even when the ISBT was suboptimal or NRTI resistance was present at baseline. These findings are not explained by the use of PI/ritonavir-containing ISBT.
在“航行”研究中，对于既往接受过治疗、初治且对≥2类抗逆转录病毒药物耐药的HIV-1感染者，多替拉韦与拉替拉韦相比显示出更好的病毒学疗效。在48周内，多替拉韦治疗组出现治疗中出现耐药导致病毒学失败的患者明显少于拉替拉韦治疗组。研究者选择的背景治疗（ISBT）包括至少一种基于耐药性分析选择的完全活性药物。对符合方案定义的病毒学失败（PDVF）患者基线和失败时的样本进行了基因型和表型耐药性检测。对“航行”研究（N = 715；354例多替拉韦，361例拉替拉韦）进行的事后分析评估了由ISBT活性、耐药谱和治疗史定义的亚组中的疗效。当ISBT仅包含核苷类逆转录酶抑制剂（NRTIs）时，多替拉韦治疗组0%（0/32）的患者发生PDVF，拉替拉韦治疗组为21.9%（7/32）（p = .005）。在携带M184V且ISBT包含拉米夫定或恩曲他滨加第二种NRTI的患者中，多替拉韦治疗组0%（0/13）和拉替拉韦治疗组33.3%（4/12）的患者发生PDVF（p = .026）。在接受含蛋白酶抑制剂（PI）ISBT治疗的患者中,多替拉韦治疗组6.0%（18/300）的患者与拉替拉韦治疗组11.8%（36/305） 的患者发生PDVF（p = .012）。达芦那韦/利托那韦是130例多替拉韦治疗患者和145例拉替拉韦治疗患者ISBT的一部分；分别有6例（4.6%）和12例（8.3%）发生PDVF（差异-3.7%；95%置信区间：-10.1%至2.5%；p = .256）。在既往接受过治疗、初治的受试者中，接受多替拉韦与拉替拉韦治疗时，即使ISBT欠佳或基线时存在NRTI耐药，病毒学失败也无或较少。这些发现无法用含PI/利托那韦的ISBT来解释。
