Ogbuagu Onyema, Molina Jean-Michel, Chetchotisakd Ploenchan, Ramgopal Moti N, Sanchez William, Brunetta Jason, Castelli Francesco, Crofoot Gordon E, Hung Chien-Ching, Ronot-Bregigeon Sylvie, Margot Nicolas A, Wang Hui, Dvory-Sobol Hadas, Rhee Martin S, Segal-Maurer Sorana
Yale School of Medicine, New Haven, Connecticut, USA.
Université de Paris Cité, Paris, France.
Clin Infect Dis. 2025 Mar 17;80(3):566-574. doi: 10.1093/cid/ciae423.
Lenacapavir is a long-acting human immunodeficiency virus type 1 (HIV-1) capsid inhibitor for treatment of HIV-1 infection. We evaluated the efficacy and safety of lenacapavir in combination with an investigator-selected optimized background regimen (OBR) after 104 weeks in adults with multidrug-resistant HIV-1.
This ongoing, international, Phase 2/3 trial at 42 sites included 72 adults with multidrug-resistant HIV-1. Following a 2-week oral lenacapavir loading phase, participants received subcutaneous lenacapavir every 26 weeks with an OBR. HIV-1 RNA, CD4 cell counts, and adverse events were assessed over 104 weeks. One participant did not enter the extension phase.
At Week 104, 44 of 71 participants (62%, 95% confidence interval [CI]: 50; 73) had HIV-1 RNA <50 copies/mL via US Food and Drug Administration (FDA) snapshot algorithm. When missing data (including discontinuations) were excluded, 44 of 54 participants (82%) had HIV-1 RNA <50 copies/mL at Week 104, mean CD4 cell count increased by 122 cells/µL (95% CI: 80; 165), and the proportion of participants with CD4 cell count <200 cells/µL decreased from 64% (46 of 72) at Baseline to 29% (16 of 55). Fourteen participants had treatment-emergent lenacapavir resistance; 7 resuppressed (HIV-1 RNA <50 copies/mL) while maintaining lenacapavir use. There were no Grade 4 or serious treatment-related adverse events. One participant discontinued study drug due to an injection site reaction.
Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks. Lenacapavir represents an important treatment option in people with multidrug-resistant HIV-1.
来那卡帕韦是一种长效的1型人类免疫缺陷病毒（HIV-1）衣壳抑制剂，用于治疗HIV-1感染。我们评估了来那卡帕韦联合研究者选择的优化背景方案（OBR）在多药耐药HIV-1成人患者中治疗104周后的疗效和安全性。
这项正在进行的国际2/3期试验在42个地点开展，纳入了72例多药耐药HIV-1成人患者。在为期2周的来那卡帕韦口服导入期后，参与者每26周接受一次皮下注射来那卡帕韦，并联合OBR。在104周内评估HIV-1 RNA、CD4细胞计数和不良事件。有一名参与者未进入延长期。
在第104周时，根据美国食品药品监督管理局（FDA）的快速算法，71名参与者中有44名（62%，95%置信区间[CI]：50；73）的HIV-1 RNA<50拷贝/毫升。排除缺失数据（包括停药情况）后，54名参与者中有44名（82%）在第104周时HIV-1 RNA<50拷贝/毫升，CD4细胞计数平均增加了122个/微升（95%CI：80；165），CD4细胞计数<200个/微升的参与者比例从基线时的64%（72例中的46例）降至29%（55例中的16例）。14名参与者出现了来那卡帕韦治疗中出现的耐药；7名在继续使用来那卡帕韦的情况下病毒载量再次被抑制（HIV-1 RNA<50拷贝/毫升）。没有4级或严重的治疗相关不良事件。有一名参与者因注射部位反应而停用研究药物。
皮下注射来那卡帕韦联合OBR治疗耐受性良好，在104周内病毒学抑制率较高。来那卡帕韦是多药耐药HIV-1感染者的重要治疗选择。
