Division of Infectious Diseases and Travel Medicine, Georgetown University Medical Center, Washington, DC.
Department of HIV Medicine, Royal Free Hospital, London, United Kingdom.
J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):801-805. doi: 10.1097/QAI.0000000000002642.
In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through week 48. Here, we present long-term efficacy and safety outcomes through week 144 of the DRIVE-SHIFT trial.
This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at day 1 [immediate switch group (ISG); n = 447] or week 24 [delayed switch group (DSG); n = 209]. Nine ISG participants who completed week 48 but did not enter extension-1 were excluded from week 144 efficacy analyses.
At week 144, HIV-1 RNA <50 copies/mL was maintained in 80.1% of the ISG (351/438) and 83.7% of the DSG (175/209), while 2.7% (12/438) and 4.8% (10/209), respectively, had HIV-1 RNA ≥50 copies/mL (Food and Drug Administration Snapshot approach). Protocol-defined virologic failure after switch occurred in 2.1% of ISG (9/438) and 3.3% of DSG (7/209); no viral resistance to doravirine was detected in 4 participants with samples available. Reductions in fasting lipids were observed at 24 weeks after switch and maintained through week 144. The mean weight change from switch to week 144 was +1.4 kg for ISG and +1.2 kg for DSG. The most common adverse events were nasopharyngitis (16.2%), headache (12.3%), and diarrhea (9.1%). Overall, 4.1% discontinued because of adverse events, and no deaths occurred.
These results confirm that switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in adults considering a change in therapy.
ClinicalTrials.gov NCT02397096.
DRIVE-SHIFT 试验的初步分析显示，转换为多伟拉韦/拉米夫定/替诺福韦酯富马酸（DOR/3TC/TDF）治疗可在第 48 周时维持对 HIV-1 的抑制。在此，我们报告 DRIVE-SHIFT 试验的第 144 周时的长期疗效和安全性结果。
这是一项 3 期、随机、开放标签试验，评估了在 HIV-1 抑制时间≥6 个月且无既往病毒学失败的成人中，从稳定的抗逆转录病毒治疗方案转换为每日一次 DOR/3TC/TDF 的疗效。参与者在第 1 天（立即转换组 [ISG]；n=447）或第 24 天（延迟转换组 [DSG]；n=209）转换。在完成第 48 周但未进入扩展 1 期的 9 名 ISG 参与者被排除在第 144 周疗效分析之外。
在第 144 周时，ISG（351/438）中 80.1%和 DSG（175/209）中 83.7%的 HIV-1 RNA<50 拷贝/mL，而分别有 2.7%（12/438）和 4.8%（10/209）的 HIV-1 RNA≥50 拷贝/mL（食品和药物管理局快照方法）。ISG（9/438）和 DSG（7/209）中分别有 2.1%和 3.3%的患者发生方案定义的病毒学失败；在 4 名可获得样本的患者中未检测到对多伟拉韦的病毒耐药性。转换后 24 周时观察到空腹血脂降低，并在第 144 周时保持稳定。从转换到第 144 周时，ISG 的平均体重变化为+1.4kg，DSG 的平均体重变化为+1.2kg。最常见的不良事件是鼻咽炎（16.2%）、头痛（12.3%）和腹泻（9.1%）。总体而言，4.1%的患者因不良事件停药，无死亡病例。
这些结果证实，对于考虑改变治疗方案的成年人，每日一次 DOR/3TC/TDF 治疗是一种通常耐受良好的维持病毒抑制的选择。
ClinicalTrials.gov NCT02397096。
