HIV antibody VRC01 does not produce viral suppression

The HIV antibody VRC01 produced a slight delay in viral rebound among patients with HIV who had interrupted ART, but was not effective for suppressing the virus, according to data from two clinical trials.

“Therapeutic administration of monoclonal antibodies has revolutionized treatment options in oncology, rheumatology, endocrinology, gastroenterology, neurology and the field of infectious diseases,” Katharine J. Bar, MD, of the University of Pennsylvania and Children’s Hospital of Philadelphia, and colleagues wrote. “Preclinical studies of single and combination broadly neutralizing antibodies in animal models have shown virus suppression, enhanced viral killing, augmented anti-HIV immune responses and reduction of the cellular reservoir. Collectively, these findings suggest that passive immunotherapy with VRC01 could potentially prevent plasma viral rebound in HIV-infected persons after analytic treatment interruption.”

The researchers conducted two open-label trials of 24 patients with HIV, all of whom discontinued ART after receiving an initial dose of VRC01. The primary outcome of the A5340 trial, conducted on 14 patients at the University of Pennsylvania and University of Alabama, was to determine the safety of the antibody. The other trial, conducted at the NIH in Bethesda, Maryland, included 10 patients and aimed to determine the possible adverse effects and efficacy of VRC01.

Twenty-two patients were men. One patient experienced a serious alcohol-related adverse event; however, there were no other serious adverse events. Median time to viral rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial, Bar and colleagues reported. Patients in both studies were more likely to have viral suppression by week 4 than historical controls (38% vs. 13%; P = .04 for A5340 trial and 80% vs. 13%; P < .001 for NIH trial).

“Our results suggest that the prevalence of clinically significant archived resistance to VRC01 may present a considerable challenge in the use of broadly neutralizing antibodies as therapeutic agents for HIV infection,” the researchers wrote. “Analogous to current regimens of highly successful combination ART that targets multiple HIV gene products, our data suggest that immunotherapy will probably require multiple broadly neutralizing antibodies that target different sites on the HIV envelope glycoprotein.” – by Andy Polhamus

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