HIV Blocked in Part with Broadly Neutralizing Antibody

A broadly neutralizing antibody was successful in blocking about a third of HIV infections but mutating strains were able to bypass the drug and infect people, according to a report of two randomized trials published in The New England Journal of Medicine.

Investigators from the Fred Hutchinson Cancer Research Center enrolled cisgender men and transgender persons at risk for HIV in the first trial and at-risk women in sub-Saharan Africa in the second trial in order to determine whether a broadly neutralizing antibody (bnAb) can be used to prevent HIV acquisition. Patients were randomly assigned to receive either infusions of a bnAb at a dose of either 10 or 30 mg/kg (a low- and high-dose group) or placebo every 8 weeks for 10 total infusions. The patients were tested for HIV every 4 weeks.

Among the 2699 participants in the men’s and transgender person’s trial, the investigators observed 32 infections in the low-dose group, 28 in the high-dose group, they said. The investigators said the HIV incidence per 100 person-years in the trial was 2.35 in the combined treatment groups (both low- and high-dose) and 2.98 in the placebo group.

Among the 1924 person’s in the women’s trials, the investigators observed 28 infections in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. This equated to an incidence infection per 100 person-years in the trial of 2.49 in the treatment group and 3.10 in the placebo group.

About 30 percent of HIV strains that were circulating in each community were blocked, but the other 70 percent of strains were able to pass through. The investigators said the specific bnAb itself was not an effective candidate for HIV prevention.

“We can use this assay to develop more potent broadly neutralizing antibodies, and there’s a likelihood with this tool we can look for new ones that are better, more potent and cheaper,” trial leader Larry Corey, MD, said.

In a related editorial, Bruce D. Walker, MD from Mass General wrote that success with bnAbs for a prevention of HIV will require a “formidable task” in the form of multiple sequential immunogens to guide the affinity maturation needed for the development of the antibodies.

Corey said the current trial reminded him of his involvement in AZT trials decades ago in the sense that it was by itself effective at blocking HIV but not the rapidly mutating strains of the virus that could get around the drug.

“The test was totally predictive of what worked and what did not work,” Corey said. “Now we can use this assay for defining a more potent broadly neutralizing antibody.”