Researchers Uncover Why Some HIV Strains Escape Protection from Neutralizing Antibodies

Could an antibody designed to prevent HIV infection leave people vulnerable once treatment stops? A new analysis of clinical trial data suggests that a promising HIV-preventing antibody offers substantial protection against certain strains of the virus, but breakthrough infections can still occur after antibody infusions are discontinued.

Researchers examined the effectiveness of VRC01, a broadly neutralising antibody developed to prevent HIV from entering and infecting human cells.

Unlike conventional treatments that control HIV after infection, broadly neutralising antibodies are being investigated as preventive strategies capable of blocking infection before it becomes established.

The analysis, conducted by Allan deCamp and colleagues, examined data from two clinical trials involving participants in the Americas and sub-Saharan Africa.

Participants received VRC01 antibody infusions over an 80-week period, allowing researchers to assess its ability to protect against different HIV strains.

The researchers also examined infections occurring between weeks 80 and 104, after the scheduled antibody infusions had ended.

The findings revealed that VRC01 demonstrated a prevention efficacy of 66.3% against HIV strains considered highly sensitive to the antibody during the treatment period.

However, the protection was not equally effective against all viral strains.

Importantly, researchers observed breakthrough HIV infections after treatment ended, including infections involving strains with greater resistance to VRC01.

During the post-treatment follow-up period, HIV diagnoses were higher among participants previously receiving VRC01 than among those in the placebo group.

Researchers suggested that differences in susceptibility among circulating HIV strains could limit the effectiveness of prevention strategies relying on a single antibody.

The findings highlight the potential importance of combining multiple broadly neutralising antibodies that target different viral structures to provide more comprehensive protection.

Researchers also emphasised that future clinical trials should monitor participants well beyond the final antibody infusion to better understand the durability of protection.

REFERENCE: Allan decamp, et al.; Extended in vivo activity of VRC01 HIV-1 prophylaxis entails initial protective efficacy and subsequent breakthrough infections; Science Translational Medicine; DOI: 10.1126/scitranslmed.aec3480