Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
J Infect Dis. 2021 Dec 1;224(11):1916-1924. doi: 10.1093/infdis/jiab229.
Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs).
An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1-exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort.
Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1.
VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.
由于有效抗逆转录病毒预防措施存在障碍，围产期人类免疫缺陷病毒 1 型（HIV-1）仍在持续发生，而长效广泛中和单克隆抗体（bNAb）可能会减轻这些障碍。
一种延长半衰期的 bNAb，VRC01LS，在出生后以 80mg/剂的剂量皮下给予 HIV-1 暴露、非母乳喂养（队列 1，n=10）和母乳喂养（队列 2，n=11）的婴儿。队列 2 在 12 周时接受第二剂（100mg）。所有婴儿均接受抗逆转录病毒预防。比较 VRC01LS 水平与之前队列中确定的 VRC01 水平。
分别有 67%和 20%的婴儿在第 1 剂和第 2 剂后出现局部反应（所有等级≤2）。根据体重调整的 VRC01LS 剂量（平均 28.8mg/kg）皮下给药后 24 小时的平均（标准差）血浆水平为 222.3（71.6）µg/mL，在第 12 周（第 2 剂前）为 44.0（11.6）µg/mL。95%和 32%的婴儿在第 8 周和第 12 周分别达到≥50µg/mL 的预定目标。半衰期为 37-41 天。第 1 剂后 VRC01LS 水平显著高于 VRC01 剂量（20mg/kg）后的水平（P<.002）。没有婴儿感染 HIV-1。
VRC01LS 具有良好的耐受性，其药代动力学支持进一步研究更有效的长效 bNAb 作为抗逆转录病毒辅助治疗，以预防婴儿 HIV-1 传播。
