Yale University School of Medicine, New Haven, CT, USA.
New York Presbyterian-Queens, Flushing, NY, USA.
Lancet HIV. 2023 Aug;10(8):e497-e505. doi: 10.1016/S2352-3018(23)00113-3. Epub 2023 Jul 11.
Lenacapavir, a first-in-class HIV-1 capsid inhibitor, is in development as a long-acting agent for treating and preventing HIV-1. We aimed to evaluate the efficacy and safety of lenacapavir with an optimised background regimen in adults living with multidrug-resistant HIV-1 up to 52 weeks.
This ongoing, international, phase 2/3 trial at 42 sites included adults living with multidrug-resistant HIV-1. In cohort 1, 36 participants were randomly assigned (2:1) to add oral lenacapavir (600 mg, days 1 and 2; 300 mg, day 8) or placebo to an existing failing regimen. At day 15, those on oral lenacapavir received subcutaneous lenacapavir 927 mg every 26 weeks; those on placebo started lenacapavir (2-week oral lead-in then subcutaneous). Cohort 1 started an optimised background regimen on day 15. In cohort 2 (non-randomised), 36 participants started an optimised background regimen concurrent with lenacapavir (oral to subcutaneous). Here we report the secondary endpoints of plasma HIV-1 RNA of less than 50 copies per mL or less than 200 copies per mL at week 52 (US Food and Drug Administration snapshot algorithm) in cohort 1 along with results for cohorts 1 and 2 combined. This trial is registered with ClinicalTrials.gov, NCT04150068, and clinicaltrialregister.eu, EudraCT 2019-003814-16 and is ongoing.
Of 72 participants, 46 (64%) had CD4 counts of less than 200 cells per μL and 38 (53%) had no more than one fully active antiretroviral drug at baseline. In cohort 1, 30 of 36 participants (83%, 95% CI 67-94) had less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) had less than 200 HIV RNA copies per mL, at week 52. In all, nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance; four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. One participant discontinued study drug owing to injection site reaction.
In participants with multidrug-resistant HIV-1, subcutaneous lenacapavir in combination with an optimised background regimen resulted in a high rate of virological suppression up to 52 weeks.
Gilead Sciences.
利纳卡帕韦是一种首创的 HIV-1 衣壳抑制剂，目前正在开发中，作为一种长效药物，用于治疗和预防 HIV-1。我们旨在评估利纳卡帕韦与优化背景治疗方案联合用于治疗最多 52 周的多重耐药 HIV-1 成人患者的疗效和安全性。
这是一项正在进行的、国际性的、在 42 个地点开展的 2/3 期临床试验，纳入了多重耐药 HIV-1 成人感染者。在队列 1 中，36 名参与者被随机（2:1）分配至加用口服利纳卡帕韦（第 1 天和第 2 天 600 mg，第 8 天 300 mg）或安慰剂至现有失败治疗方案。在第 15 天，接受口服利纳卡帕韦的患者接受每 26 周皮下注射利纳卡帕韦 927 mg；接受安慰剂的患者开始利纳卡帕韦（2 周口服导入期后皮下注射）。队列 1 在第 15 天开始优化背景治疗方案。在队列 2（非随机）中，36 名参与者同时开始接受优化背景治疗方案和利纳卡帕韦治疗。在此，我们报告了队列 1 中第 52 周时血浆 HIV-1 RNA 低于 50 拷贝/ml 或低于 200 拷贝/ml 的次要终点（美国食品和药物管理局快照算法），以及队列 1 和队列 2 的汇总结果。该试验在 ClinicalTrials.gov、NCT04150068、clinicaltrialregister.eu 注册，EudraCT 编号为 2019-003814-16，正在进行中。
72 名参与者中，46 名（64%）CD4 计数小于 200 个细胞/μL，38 名（53%）基线时仅有不超过一种完全有效的抗逆转录病毒药物。在队列 1 中，36 名参与者中有 30 名（83%，95%CI 67-94）在第 52 周时 HIV-1 RNA 低于 50 拷贝/ml，36 名参与者中有 31 名（86%，71-95）在第 52 周时 HIV RNA 低于 200 拷贝/ml。共有 9 名参与者（队列 1 中 4 名，队列 2 中 5 名）出现利纳卡帕韦耐药性；4 名耐药性恢复（HIV-1 RNA<50 拷贝/ml），同时维持利纳卡帕韦使用。1 名参与者因注射部位反应停止使用研究药物。
在多重耐药 HIV-1 感染者中，皮下注射利纳卡帕韦联合优化背景治疗方案可在长达 52 周的时间内实现高病毒学抑制率。
吉利德科学公司。
