Project Details

PedMAb1-Ex: Preventing pediatric HIV with broadly neutralizing anti-HIV-1 monoclonal antibodies

Terusha Chetty, MBChB, PhD

Summary

BACKGROUND: Despite remarkable progress in preventing HIV transmission to children, nearly 120,000 children still acquire HIV annually due to prolonged exposure during breastfeeding in communities with high HIV prevalence. Despite high maternal antiretroviral therapy (ART) coverage, postnatal transmission persists due to incident infection, delayed ART initiation, and incomplete viral suppression. GAP: A long-acting HIV broadly neutralizing antibody (bNAb) could bridge the breastfeeding risk window and provide months of protection independent of maternal adherence to ARTs. HYPOTHESIS: The PedMAb Consortium hypothesizes that bNAbs administered to breastfeeding HIV-exposed neonates and infants born without HIV, alone or in combination, in high HIV prevalence settings like South Africa are safe, long-acting and provide excellent coverage of HIV, and may be critical to eliminate pediatric HIV. METHODS: The pediatric trial will follow the adult trial establishing safety. The Phase I trial, PedMAb1-Ex, will enrol 32 HIV-exposed neonates without HIV. The study is conducted at the South African Medical Research Council’s (SAMRC’s) Chatsworth clinical research site. The first two randomized arms will determine the safety and pharmacokinetics (PK) of bNAb ePGT121v1-LS when given SC or IM at a fixed dose following birth. Two additional arms will determine the safety and PK of ePGT121v1-LS with a complementary bNAb, at a fixed dose following birth, and at 3 months. RESULTS: Pending. IMPACT: BNAbs represents a transformative strategy for vertical HIV transmission prevention during breastfeeding, where the burden of pediatric HIV remains unacceptably high. Testing a novel, engineered bNAb in infants positions this intervention for its most impactful use-case. Website Link: SAMRC and Ospedale San Raffaele Launch Phase I Trial of Long-Acting HIV Prevention Antibody | SAMRC