Mahomed Sharana, Osman Farzana, Beliveau Martin, Heredia-Ortiz Roberto, Carlton Kevin, Wang Jennifer, Mughal Madeeha, Low Kwang, Narpala Sandeep, Lin Bob C, Castro Mike, Serebryannyy Leonid, Koup Richard A, Karim Quarraisha Abdool, Abdool Karim Salim S
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
Department of Medical Microbiology, School of Laboratory Medicine, University of KwaZulu-Natal, Durban, South Africa.
Nat Commun. 2025 Sep 1;16(1):8177. doi: 10.1038/s41467-025-63051-8.
Broadly neutralizing antibodies (bNAbs) offer a promising strategy for HIV prevention. Subcutaneous (SC) administration is more feasible than intravenous delivery but may be limited by prolonged administration times and multiple injections. Here we report a pharmacokinetic (PK) modelling study, an unspecified exploratory analysis that involved 57 HIV-negative African women (median age 25 years; BMI range 18.1-39.3 kg/m²) enrolled in the CAPRISA 012B trial (PACTR202003767867253, total participants n = 76). A predefined sub-analysis directly comparing the 20 mg/kg dose level of ENHANZE™ drug product (EDP) versus no-EDP was conducted in a subset of participants (n = 5 with EDP, n = 5 without). CAP256V2LS and VRC07-523LS-potent HIV-1 bNAbs targeting conserved envelope epitopes-were administered SC with and without EDP. The primary outcome of this sub-analysis was duration of administration. Secondary outcomes included PK and safety. Among the subset of participants (n = 10), EDP significantly reduced median administration time from 49.5 to 10.0 minutes and reduced injections per dose from 3 to 1. CAP256V2LS and VRC07-523LS concentrations at 24 weeks post-dose, were 4.8- and 3.0-fold higher, respectively, with EDP. CAP256V2LS exposure (AUC) increased by 40%, despite a 30% decrease in Cmax. EDP was well tolerated with no safety concerns. These findings support EDP-enhanced SC delivery as a scalable and simplified strategy for long-acting antibody-based HIV prevention.
广泛中和抗体（bNAbs）为预防HIV提供了一种有前景的策略。皮下注射比静脉注射更可行，但可能受给药时间长和多次注射的限制。在此，我们报告一项药代动力学（PK）建模研究，这是一项未明确说明的探索性分析，纳入了参与CAPRISA 012B试验（注册号PACTR202003767867253，总参与者n = 76）的57名HIV阴性非洲女性（中位年龄25岁；BMI范围18.1 - 39.3kg/m²）。在一部分参与者（n = 5接受增强型药物产品（EDP），n = 5未接受）中进行了一项预先定义的亚分析，直接比较20mg/kg剂量水平的ENHANZE™药物产品（EDP）与无EDP的情况。针对保守包膜表位的强效HIV-1 bNAbs CAP256V2LS和VRC07 - 523LS在有和无EDP的情况下进行皮下给药。该亚分析的主要结局是给药持续时间。次要结局包括药代动力学和安全性。在这部分参与者（n = 10）中，EDP显著将中位给药时间从49.5分钟减少至10.0分钟，并将每剂注射次数从3次减少至1次。给药后24周时，使用EDP时CAP256V2LS和VRC07 - 523LS的浓度分别高出4.8倍和3.0倍。尽管Cmax降低了30%，但CAP256V2LS的暴露量（AUC）增加了40%。EDP耐受性良好，无安全性问题。这些发现支持将EDP增强的皮下给药作为一种可扩展且简化的基于长效抗体的HIV预防策略。
