Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials.

VRC01 prophylaxis induces escape mutations in HIV post-infection in 31% of treated individuals, highlighting challenges in antibody-based prevention.

• Why it matters: Understanding how HIV evolves under bnAb pressure is crucial for developing durable prevention strategies, as escape mutations can undermine antibody efficacy.
• What they did: Analyzing 11,730 HIV envelope sequences from 47 AMP trial participants, researchers identified VRC01-mediated escape mutations in 8 of 26 treated individuals, but not in placebo recipients.
• The result: Escape mutations, mainly in Env Loop-D and β23/V5 regions, confer cross-resistance but are rare in circulating viruses, emphasizing the need for next-generation bnAbs with broader and more potent activity.