VRC01 antibody in two HIV trials: 66.3% efficacy against sensitive strains, later resistant cases

A team led by Allan deCamp analyzed data from two parallel antibody-mediated prevention (AMP) efficacy trials, HVTN 704 and HPTN 085, conducted in the Americas and sub-Saharan Africa. The results were published in Science Translational Medicine on 4 November 2026. The trials tested whether intravenous infusion of VRC01, a broadly neutralizing antibody that targets the CD4 binding site, prevents HIV-1 acquisition. This analysis covers HIV-1 acquisition through the week 104 final study visit doi.orgScience Translational Medicinedoi.orgOpen source ↗.

Protection against sensitive viruses

Against viruses considered highly sensitive to VRC01, defined by an 80% inhibitory concentration (IC80) below 1 microgram/milliliter, VRC01 prophylaxis maintained a cumulative prevention efficacy of 66.3% (95% confidence interval: 32.4 to 83.2%) doi.orgScience Translational Medicinedoi.orgOpen source ↗. According to the authors, this suggests that the antibody successfully blocked or cleared such infections doi.orgScience Translational Medicinedoi.orgOpen source ↗.

The researchers note that VRC01 has recently moved into large-scale clinical trials. The open question is whether it can give meaningful protection against the many circulating HIV strains, which keep evolving.

Infections after the last dose

The final dose was given at week 72. The authors focused on the period after week 80, up to week 104. In that period, HIV diagnosis and resistance to VRC01 were more frequent and greater in the VRC01 groups than in the placebo groups doi.orgScience Translational Medicinedoi.orgOpen source ↗.

For example, diagnoses with viruses considered moderately sensitive or resistant to VRC01 (IC80 of 5 microgram/milliliter or higher) numbered 11 in the VRC01 groups versus 1 in the placebo groups doi.orgScience Translational Medicinedoi.orgOpen source ↗.

The authors suggest a plausible explanation. As the concentration of VRC01 in the body declined, viruses that had been suppressed, often evolving greater resistance under selective pressure, emerged as detectable infections doi.orgScience Translational Medicinedoi.orgOpen source ↗.

Conclusions of the authors

The authors conclude that single antibodies can block sensitive strains, but multiple antibodies are likely required to prevent both viral escape and infections that appear after the antibody level falls doi.orgScience Translational Medicinedoi.orgOpen source ↗. They also write that the results bear on the design and analysis of future trials of broadly neutralizing antibodies against HIV-1. One example is the importance of testing for the virus long after infusions have ended.