Background Breastmilk optimizes child survival in low-middle income high HIV prevalence settings. However, breastmilk transmission of HIV-1 continues to contribute to residual vertical HIV transmission. The Phase 1 PedMAb clinical trial aims to define the optimal doses, ideal combination and timing of subcutaneous (SC) administration of two HIV-1 broadly neutralizing antibodies (bNAbs), VRC07-523LS and CAP256V2LS, separately or in combination, to prevent breastmilk transmission of HIV-1 in high incidence regions such as South Africa. The trial is being conducted at the South African Medical Research Council Chatsworth Clinical Research site and the RK Khan hospital. Here we first report the reactogenicity and safety events of CAP256V2LS for the first time in infants.

Methods Between 1^st September and end of October 2022, 8 eligible HIV exposed uninfected infants received 5mg/kg CAP256V2LS SC, within 72 hours of birth. All infants were observed for 4 hours post-dose, and followed up face-to-face at days 3, 14 and 28 post-dose for primary objective safety assessments, and until 6 months for secondary objective. A pictorial study diary handed to mothers and collected at day 14 post-dose helped mothers document reactogenicity and early adverse events (AEs). An internal study safety committee reviewed all safety data every two weeks. The Division of AIDS Table, version 2.1. July 2017, was used to grade AEs.

Results No reactogenicity events were observed at 4 hours or over the first 3 days post-dose. Thirteen AEs were documented during the 28-days post-bNAb administration, mostly common illnesses (except for low absolute neutrophils, a palatal cyst and an uncomplicated umbilical hernia); other 20 AEs were recorded during the following 5 months. AEs were deemed unrelated to study product.

Conclusion CAP256V2LS administered SC at 5mg/kg to infants within 72 hours of birth is safe. The trial is proceeding to test bNAb’s safety at a higher dose (10mg/kg).