Smith Graham H R, Henry W Keith, Podzamczer Daniel, Masiá Maria Del Mar, Bettacchi Christopher J, Arasteh Keikawus, Jaeger Hans, Khuong-Josses Marie-Aude, Montes-Ramírez Maria Luisa, Stellbrink Hans-Jürgen, Yazdanpanah Yazdan, Richmond Gary J, Sutton Kenneth C, Zhang Feifan, McCoig Cynthia C, St Clair Marty H, Vandermeulen Kati, Van Solingen-Ristea Rodica, Smith Kimberly Y, Margolis David A, Spreen William R
Maple Leaf Research, Toronto, Ontario, Canada.
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
Open Forum Infect Dis. 2021 Aug 25;8(9):ofab439. doi: 10.1093/ofid/ofab439. eCollection 2021 Sep.
In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years.
After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs).
At week 256, 186 of 230 (81%) participants in randomized Q8W/Q4W groups and 41 of 44 (93%) participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after week 48. Injection wsite reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant.
Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection.Clinical Trials Registration. NCT02120352.
在长效抗逆转录病毒治疗启用试验2（LATTE - 2）2b期研究中，每8周（Q8W）或每4周（Q4W）给药一次的长效（LA）注射用卡博特韦+利匹韦林，在初治的1型人类免疫缺陷病毒（HIV - 1）成人患者中，与每日口服抗逆转录病毒疗法（ART）相比，在96周内疗效相当。在此，我们报告卡博特韦+利匹韦林长效制剂在约5年时间内的疗效、耐受性和安全性。
在口服卡博特韦+阿巴卡韦/拉米夫定20周后，参与者被随机分配至卡博特韦+利匹韦林长效制剂Q8W或Q4W组，或在96周维持期继续口服ART。在为期256周的延长期，参与者继续其当前的长效制剂方案（随机Q8W/Q4W组），或从口服ART转换为Q8W或Q4W长效制剂治疗（延长期转换组）。评估的终点包括HIV - 1 RNA<50拷贝/mL的参与者比例（快照算法）和不良事件（AE）。
在第256周时，随机Q8W/Q4W组的230名参与者中有186名（81%）、延长期转换组的44名参与者中有41名（93%）的HIV - 1 RNA<50拷贝/mL。在第48周后未发生方案定义的病毒学失败。注射部位反应很少导致停药（随机Q8W/Q4W组和延长期转换组分别有4名[2%]和1名[2%]参与者）。随机Q8W/Q4W组有3名参与者发生与药物相关的严重AE，包括1例致命严重AE（Q4W组）；延长期转换组未发生。在25名因AE导致停药的参与者中，20名在随机Q4W组；没有导致停药的AE发生在超过1名参与者身上。
卡博特韦+利匹韦林长效制剂表现出长期疗效和耐受性，证明其作为HIV - 1感染维持治疗的持久性。临床试验注册。NCT02120352。
