Fundación Huésped, Research Department, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Fundación Huésped, Research Department, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Int J Antimicrob Agents. 2024 Oct;64(4):107301. doi: 10.1016/j.ijantimicag.2024.107301. Epub 2024 Aug 14.
Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine.
The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508).
Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n=165) or the dual therapy arm (n=171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P=0.04). Two toxicity-related events led to discontinuation in each group.
Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients.
含替诺福韦的抗逆转录病毒治疗方案可能具有长期毒性相关的副作用。本研究旨在比较达拉韦林/利托那韦联合拉米夫定与达拉韦林/利托那韦联合替诺福韦和恩曲他滨或拉米夫定的病毒学疗效。
ANDES 研究是一项 48 周、4 期、随机、开放标签、非劣效性试验，纳入了初治人类免疫缺陷病毒（HIV）感染者。患者以 1:1 的比例随机接受每日口服治疗方案，一组为基于通用达拉韦林/利托那韦（800/100mg）与通用拉米夫定 300mg 片的双药治疗，另一组为达拉韦林/利托那韦联合替诺福韦/恩曲他滨（300/200mg）或替诺福韦/拉米夫定（300/300mg）的三药治疗。主要终点是意向治疗人群中第 48 周时病毒载量<50 拷贝/ml 的患者比例。采用美国食品和药物管理局快照算法和-12%的非劣效性边界。次要目标是分析方案人群中的安全性。该研究已在 ClinicalTrials.gov（NCT02770508）注册。
2015 年 11 月至 2020 年 10 月 31 日，336 名参与者被随机分配至三药治疗组（n=165）或二药治疗组（n=171）。48 周后，三药治疗组 153 名（93%）和二药治疗组 155 名（91%）患者达到病毒学抑制（差异-2.1%，95%置信区间-7.0 至 2.9）。三药治疗组药物相关不良事件更常见（P=0.04）。两组各有 2 例与毒性相关的事件导致停药。
与包括替诺福韦的标准三药治疗方案相比，初治患者使用联合通用达拉韦林/利托那韦和拉米夫定的复方制剂显示出非劣效性和更安全的毒性特征。
