Hyaluronidase-enhanced subcutaneous delivery of bNAbs: a phase 1 randomized controlled clinical trial in HIV-uninfected women

Sharana Mahomed (), Farzana Osman, Martin Beliveau, Roberto Heredia-Ortiz, Kevin Carlton, Jennifer Wang, Madeeha Mughal, Kwang Low, Sandeep Narpala, Bob C. Lin, Mike Castro, Leonid Serebryannyy, Richard A. Koup, Quarraisha Abdool Karim and Salim S. Abdool Karim
Additional contact information
Sharana Mahomed: Centre for the AIDS Programme of Research in South Africa (CAPRISA)
Farzana Osman: Centre for the AIDS Programme of Research in South Africa (CAPRISA)
Martin Beliveau: Certara
Roberto Heredia-Ortiz: Certara
Kevin Carlton: National Institutes of Health
Jennifer Wang: National Institutes of Health
Madeeha Mughal: National Institutes of Health
Kwang Low: National Institutes of Health
Sandeep Narpala: National Institutes of Health
Bob C. Lin: National Institutes of Health
Mike Castro: National Institutes of Health
Leonid Serebryannyy: National Institutes of Health
Richard A. Koup: National Institutes of Health
Quarraisha Abdool Karim: Centre for the AIDS Programme of Research in South Africa (CAPRISA)
Salim S. Abdool Karim: Centre for the AIDS Programme of Research in South Africa (CAPRISA)

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-63051-8

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