HIV-Specific Broadly Neutralizing Antibody Minimally Impacts Time to Viral Rebound Following ART Interruption

A broadly neutralizing antibody (bNAb) in virally suppressed individuals was associated with a modestly delayed HIV viral rebound after interruption of antiretroviral therapy (ART).

VRC01 is a bNAb that inhibits multiple strains of HIV by adhering to the CD4 binding site. In a new study, investigators evaluated the use of VRC01 in a small cohort of Thai men diagnosed with HIV who initiated ART within the first month of infection and had been virally suppressed for approximately 3 years.

“This is the first time that the VRC01 antibody has been evaluated in people who started ART during acute HIV infection,” said investigators Dr Trevor Crowell. “We hypothesized that VRC01 might be more effective at suppressing HIV in the bloodstream of these volunteers than had been observed in people who started ART during the chronic phase of infection. These volunteers had a smaller HIV reservoir and less viral diversity, meaning they were less likely to have preexisting resistance to the antibody.”

A total of 18 individuals with undetectable viral loads were randomized to receive either VRC01 or placebo. Each participant received infusions at the time of ART interruption and every 3 weeks after for up to 24 weeks. The infusions were stopped if the virus was detected in the blood and ART was restarted.

Among patients in the VRC01 arm, the results of the study showed a delay in viral rebound that occurred at a median of 26 days compared with 14 days in the placebo arm. ART was reinitiated in 17 of 18 participants who experience viral rebound.

One participant in the VRC01 arm was virally suppressed for 42 weeks after ART interruption; however, their viral loads became detectable again within the last few days.

“Although the delayed time to viral load rebound with VRC01 seen here is likely not clinically significant, it taught us 2 important lessons,” said investigator Dr Jintanat Ananworanich. “It provides the basis for future studies in early treated people with combination bNAbs of higher potency, and we can now investigate the samples from this study to identify factors that might have contributed to the delay in rebound.”

The study is 1 of several functional cure studies being conducted in the acute affection cohort to identify acutely infected individuals and place them onto ART immediately. The authors noted that very early initiation of ART leads to immune restoration and an extremely small undetectable reservoir of HIV DNA.

The study is the first randomized, controlled trial to demonstrate this effect of VRC01. The findings were presented at the annual IAS Conference on HIV Science in Paris.