Skiest Daniel J, Cohen Calvin, Mounzer Karam, Haigney Zach, Barker David, Gottlieb Michael, Bellman Paul C, Dejesus Edwin, Khanlou Homayoon, Ruane Peter J, Hsiao Chiu-Bin, Abriola Kenneth, Rashbaum Bruce, Bellos Nicholaos, Ward Douglas, Colson Amy, Santiago Frances, Habel Anne, Garb Jane
Division of Infestious Diseases, Baystate Medical Center, Springfield, Massachusetts 01199, USA.
HIV Clin Trials. 2011 May-Jun;12(3):131-40. doi: 10.1310/hct1203-131.
Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population.
Medical records of subjects who received raltegravir as part of the Merck EAP study 0518 were reviewed and abstracted at participating sites. Eligibility criteria included HIV positivity, age ≥ 16 years, limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, detectable viremia on current treatment regimen, and documented resistance to at least one drug in each antiretroviral class (PI, NNRTI, and nucleoside analogue). Demographic, clinical, and laboratory data were collected locally using a standardized collection form. Genotypic susceptibility scores (GSS) were determined from the most recent genotypic resistance test available prior to the initiation of raltegravir. The main objective was to compare virologic results in patients who received raltegravir with a PI versus those who received raltegravir without a PI.
Four hundred forty-two subjects were evaluated from the respective sites in the EAP trial, of whom 340 were evaluable. The baseline mean HIV RNA was 4.6 log copies/ mL, and the mean CD4 cell count was 159 cells/μL. The median number of total and new antiretroviral agents in the background regimen was 4 and 2, respectively. Among the 254 patients who received a PI, the most common PI used was darunavir (89%). Etravirine was commonly used in both groups: 39% of the PI group and 67% of the non-PI group. At week 12, 67% of PI patients and 64% of non-PI patients achieved HIV RNA <75 copies/mL and 85% and 86%, respectively, achieved HIV RNA <400 copies/mL GSS, which was similar in both groups at baseline, predicted achieving an HIV RNA of <400 and 75 copies/mL at week 12 (P < .05).
In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI (used with etravirine in two-thirds of patients) had similar virologic activity when compared to more standard regimens using raltegravir with a PI. The main determinant of efficacy was the number of active drugs as measured by GSS. These data expand the potential utility of raltegravir in patients with multidrug-resistant HIV.
对多种药物耐药的HIV-1患者的治疗选择有限。整合酶抑制剂拉替拉韦与蛋白酶抑制剂（PIs）联合使用时，在耐药HIV-1患者中显示出优异的疗效。然而，关于在该人群中不使用PIs而单用拉替拉韦的治疗结果，可用数据有限。
在参与研究的各站点回顾并提取了作为默克EAP研究0518一部分接受拉替拉韦治疗的受试者的病历。纳入标准包括HIV阳性、年龄≥16岁、因对多种抗逆转录病毒方案耐药或不耐受而治疗选择有限或没有治疗选择、当前治疗方案下可检测到病毒血症，以及记录显示对每种抗逆转录病毒药物类别（PI、非核苷类逆转录酶抑制剂和核苷类似物）中至少一种药物耐药。使用标准化收集表在当地收集人口统计学、临床和实验室数据。根据拉替拉韦开始使用前可获得的最新基因型耐药性检测结果确定基因型易感性评分（GSS）。主要目的是比较接受拉替拉韦联合PI治疗的患者与接受拉替拉韦单药治疗的患者的病毒学结果。
在EAP试验中，各站点共评估了442名受试者，其中340名可评估。基线时HIV RNA平均水平为4.6 log拷贝/mL，CD4细胞计数平均为159个/μL。背景治疗方案中抗逆转录病毒药物的总数和新药的中位数分别为4种和2种。在接受PI治疗的254名患者中，最常用的PI是达芦那韦（89%）。依曲韦林在两组中均常用：PI组为39%，非PI组为67%。在第12周时，67%的PI组患者和64%的非PI组患者HIV RNA <75拷贝/mL，分别有85%和86%的患者HIV RNA <400拷贝/mL。基线时两组的GSS相似，GSS预测在第12周时HIV RNA <400和<75拷贝/mL（P < 0.05）。
在有治疗经验的患者中，与使用拉替拉韦联合PI的更标准治疗方案相比，拉替拉韦与不含PI的方案（三分之二的患者联合使用依曲韦林）联合使用具有相似的病毒学活性。疗效的主要决定因素是通过GSS衡量的有效药物数量。这些数据扩展了拉替拉韦在多药耐药HIV患者中的潜在应用。
