Hospital La Paz, Instituto de Investigation Sanitaria del Hospital Universitario La Paz, Madrid, Spain.
Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, Institut National de la Santé et de la Recherche Médicale UMR_S 1136, Paris, France.
Lancet Infect Dis. 2015 Jul;15(7):785-92. doi: 10.1016/S1473-3099(15)00096-1. Epub 2015 Jun 7.
Our objective was to assess therapeutic non-inferiority of dual treatment with lopinavir-ritonavir and lamivudine to triple treatment with lopinavir-ritonavir plus two nucleos(t)ides for maintenance of HIV-1 viral suppression.
In this randomised, open-label, non-inferiority trial, we recruited patients from 32 HIV units in hospitals in Spain and France. Eligible patients were HIV-infected adults (aged ≥18 years) with HIV-1 RNA of less than 50 copies per mL, for at least 6 months on triple treatment with lopinavir-ritonavir (twice daily) plus lamivudine or emtricitabine and a second nucleos(t)ide, with no resistance or virological failure to these drugs, and no positive hepatitis B serum surface antigen. Investigators at each centre randomly assigned patients (1:1; block size of four; stratified by time to suppression [<1 year or >1 year] and nadir CD4 cell count [<100 cells per μL or >100 cells per μL]; computer-generated random sequence) to continue triple treatment or switch to dual treatment (oral lopinavir 400 mg and oral ritonavir 100 mg twice daily plus oral lamivudine 300 mg once daily). The primary endpoint was response to treatment in the intention-to-treat population (all randomised patients) at 48 weeks. The non-inferiority margin was 12%. This study is registered with ClinicalTrials.gov, number NCT01471821.
Between Oct 1, 2011, and April 1, 2013, we randomly assigned 250 participants to continue triple treatment (127 [51%] patients) or switch to dual treatment (123 [49%] patients). In the intention-to-treat population, 110 (86·6%) of 127 patients in the triple-treatment group responded to treatment versus 108 (87·8%) of 123 in the dual-treatment group (difference -1·2% [95% CI -9·6 to 7·3]; p=0·92), meeting the criteria for non-inferiority. Serious adverse events occurred in eight (7%) patients in the triple-treatment group and five (4%) in the dual-treatment group (p=0·515), and study drug discontinuations due to adverse events occurred in four (3%) in the triple-treatment group and one (1%) in the dual-treatment group (p=0·223).
Dual treatment with lopinavir-ritonavir plus lamivudine has non-inferior therapeutic efficacy and is similarly tolerated to triple treatment.
AbbVie and Red Temática Cooperativa de Investigación en Sida.
我们的目的是评估洛匹那韦-利托那韦联合拉米夫定双联治疗与洛匹那韦-利托那韦联合两种核苷（酸）类药物三联治疗用于维持 HIV-1 病毒抑制的疗效非劣效性。
在这项随机、开放标签、非劣效性试验中，我们从西班牙和法国 32 家医院的 32 个 HIV 单位招募了患者。合格的患者为 HIV 感染的成年人（年龄≥18 岁），其 HIV-1 RNA 载量低于 50 拷贝/mL，至少已接受洛匹那韦-利托那韦（每日两次）联合拉米夫定或恩曲他滨和第二种核苷（酸）类药物的三联治疗 6 个月，对这些药物无耐药或病毒学失败，且乙型肝炎表面抗原血清呈阳性。每个中心的研究人员以 1:1 的比例（区组大小为 4；按抑制时间[＜1 年或＞1 年]和最低 CD4 细胞计数[＜100 个/μL 或＞100 个/μL]分层）随机分配患者（电脑生成的随机序列）继续三联治疗或转为双联治疗（口服洛匹那韦 400 mg 和利托那韦 100 mg，每日两次，联合口服拉米夫定 300 mg，每日一次）。主要终点为意向治疗人群（所有随机患者）在 48 周时的治疗反应。非劣效性边界为 12%。该研究在 ClinicalTrials.gov 注册，编号为 NCT01471821。
2011 年 10 月 1 日至 2013 年 4 月 1 日，我们随机分配 250 名参与者继续三联治疗（127[51%]名患者）或转为双联治疗（123[49%]名患者）。在意向治疗人群中，三联治疗组中有 110（86.6%）名患者对治疗有反应，双联治疗组中有 108（87.8%）名患者对治疗有反应（差值-1.2%[95%CI-9.6 至 7.3]；p=0.92），符合非劣效性标准。三联治疗组中有 8（7%）名患者发生严重不良事件，双联治疗组中有 5（4%）名患者发生严重不良事件（p=0.515），因不良事件而停止研究药物治疗的三联治疗组有 4（3%）名患者，双联治疗组有 1（1%）名患者（p=0.223）。
洛匹那韦-利托那韦联合拉米夫定双联治疗具有与三联治疗相当的疗效和耐受性。
艾伯维公司和 Red Temática Cooperativa de Investigación en Sida。
