Background

Long-acting treatment for HIV has potential to improve adherence, provide durable viral suppression, and have long-term individual and public health benefits. We evaluated treatment with two antibodies that broadly and potently neutralise HIV (broadly neutralising antibodies; bNAbs), combined with lenacapavir, a long-acting capsid inhibitor, as a long-acting regimen.

Methods

This ongoing, randomised, blind, phase 1b proof-of-concept study conducted at 11 HIV treatment centres in the USA included adults with a plasma HIV-1 RNA concentration below 50 copies per mL who had at least 18 months on oral antiretroviral therapy (ART), CD4 counts of at least 500 cells per μL, and protocol-defined susceptibility to bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). Participants stopped oral ART and were randomly assigned (1:1) to one dose of 927 mg subcutaneous lenacapavir plus an oral loading dose, 30 mg/kg intravenous teropavimab, and 10 mg/kg or 30 mg/kg intravenous zinlirvimab on day 1. Investigational site personnel and participants were masked to treatment assignment throughout the randomised period. The primary endpoint was incidence of serious adverse events until week 26 in all randomly assigned participants who received one dose or more of any study drug. This study is registered with ClinicalTrials.gov, NCT04811040.

Findings

Between June 29 and Dec 8, 2021, 21 participants were randomly assigned, ten in each group received the complete study regimen and one withdrew before completing the regimen on day 1. 18 (86%) of 21 participants were male; participants ranged in age from 25 years to 61 years and had a median CD4 cell count of 909 (IQR 687–1270) cells per μL at study entry. No serious adverse events occurred. Two grade 3 adverse events occurred (lenacapavir injection-site erythaema and injection-site cellulitis), which had both resolved. The most common adverse events were symptoms of injection-site reactions, reported in 17 (85%) of 20 participants who received subcutaneous lenacapavir; 12 (60%) of 20 were grade 1. One (10%; 95% CI 0–45) participant had viral rebound (confirmed HIV-1 RNA concentration of ≥50 copies per mL) in the zinlirvimab 10 mg/kg group, which was resuppressed on ART, and one participant in the zinlirvimab 30 mg/kg group withdrew at week 12 with HIV RNA <50 copies per mL.

Interpretation

Lenacapavir with teropavimab and zinlirvimab 10 mg/kg or 30 mg/kg was generally well tolerated with no serious adverse events. HIV-1 suppression for at least 26 weeks is feasible with this regimen at either zinlirvimab dose in selected people with HIV-1.

Funding

Gilead Sciences.

中文翻译：

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Teropavimab 和 zinlirvimab 联合 Lenacapavi 每 6 个月一次用于 HIV 治疗的安全性：一项 1b 期、随机、概念验证研究

背景

艾滋病毒的长效治疗有可能提高依从性，提供持久的病毒抑制，并具有长期的个人和公共卫生益处。我们评估了两种广泛有效中和 HIV 的抗体（广泛中和抗体；bNAb）与长效衣壳抑制剂来那卡韦联合作为长效治疗方案的治疗。

方法

这项正在进行的、随机、盲法 1b 期概念验证研究在美国 11 个 HIV 治疗中心进行，研究对象包括血浆 HIV-1 RNA 浓度低于 50 拷贝/毫升且至少接受过 18 个月口服抗逆转录病毒治疗的成年人。 ART）、CD4 计数至少为每 μL 500 个细胞，以及方案定义的对 bNAb 特罗帕维单抗 (3BNC117-LS) 和 zinlirvimab (10-1074-LS) 的敏感性。参与者停止口服 ART，并在第 1 天随机分配 (1:1) 接受一剂 927 mg 皮下注射的来那帕韦加口服负荷剂量、30 mg/kg 静脉注射特罗帕维单抗和 10 mg/kg 或 30 mg/kg 静脉注射 zinlirvimab。在整个随机期间，研究中心人员和参与者对治疗分配情况不知情。主要终点是所有随机分配的接受一剂或多剂任何研究药物的参与者直至第 26 周的严重不良事件发生率。ClinicalTrials.gov注册，NCT04811040。

发现

2021 年 6 月 29 日至 12 月 8 日期间，21 名参与者被随机分配，每组 10 名参与者接受完整的研究方案，1 名参与者在第 1 天完成方案之前退出。21 名参与者中有 18 名（86%）为男性；参与者的年龄从 25 岁到 61 岁不等，在研究开始时，CD4 细胞计数中位数为每 μL 909 (IQR 687–1270) 个细胞。没有发生严重不良事件。发生了两起 3 级不良事件（来那卡韦注射部位红斑和注射部位蜂窝织炎），但均已解决。最常见的不良事件是注射部位反应症状，20 名接受皮下注射来那卡韦的参与者中有 17 名（85%）报告了注射部位反应症状； 20 人中有 12 人 (60%) 为 1 级。在 zinlirvimab 10 mg/kg 组中，一名 (10%; 95% CI 0-45) 参与者出现病毒反弹（确认 HIV-1 RNA 浓度≥50 拷贝/mL），这种病毒在 ART 中被重新抑制，zinlirvimab 30 mg/kg 组的一名参与者在第 12 周退出，且 HIV RNA <50 拷贝/mL。

解释

来那帕韦联合特罗帕韦单抗和辛利维单抗 10 mg/kg 或 30 mg/kg 通常耐受性良好，没有严重不良事件。对于选定的 HIV-1 患者，使用任一 zinlirvimab 剂量的该方案可抑制 HIV-1 至少 26 周。

资金

吉利德科学。