Anti-HIV Antibodies Show Promise in Maintaining Viral Suppression

Imagine a world in which HIV viral suppression can be maintained without the lifelong use of antiretroviral therapy.

Well, what once seemed an impossibility may. in the not-so-distant future become reality—at least if the results of a phase 1b clinical trial published on September 27 in Nature are any indication. The authors of the paper, an international team of researchers, found that combination therapy with 2 potent monoclonal anti-HIV-1 broadly neutralizing antibodies, 3BNC117 and 10-1074, administered during analytical antiretroviral therapy treatment interruption, was able to maintain long-term viral suppression in HIV-positive individuals with antibody-sensitive viral reservoirs.

“[Our finding demonstrate] there is potential for using the antibodies to maintain [viral] control,” study co-author Michel C. Nussenzweig, MD, PhD, Zanvila A. Cohn and Ralph M. Steinman Professor and Investigator, Howard Hughes Medical Institute, The Rockefeller University, told Contagion®.

Dr. Nussenzweig and his colleagues enrolled HIV-1-infected individuals on antiretroviral therapy who were pre-screened for 3BNC117 and 10-1074 sensitivity. Study eligibility criteria included ongoing antiretroviral therapy for at least 24 months with plasma HIV-1 RNA levels of <50 copies per ml for at least 18 months (one blip <500 copies per ml was allowed) and <20 copies per ml at screening, as well as CD4+ T cell counts >500 cells per μl. Enrolled participants received 3 infusions of 30 mg/kg⁻¹ of 3BNC117 and 10-1074 each at 0, 3 and 6 weeks.

Overall, the authors reported that the infusions of the 2 antibodies were generally well-tolerated, with mild fatigue reported in 2 study subjects. Notably, the 9 enrolled study subjects with antibody-sensitive latent viral reservoirs maintained HIV-1 viral suppression for a median of 21 weeks, with a low of 15 weeks and a high of more than 30 weeks. Importantly, none of the study subjects developed viruses that were resistant to both antibodies.

“Antibody half-life can be extended by Fc domain mutation to 3- to 4-fold better than current [therapies] and such molecules are currently being tested in our clinic,” Dr. Nussenzweig said. “If we triple the interval to rebound from 15 weeks after the last dose to 45 weeks, that becomes a very long time between therapies.”

Of course, as this was a relatively small phase 1b clinical trial, much research still needs to be done to assess the viability of the use of these anti-HIV-1 monoclonal antibodies over the long term. Dr. Nussenzweig noted that he and his colleagues also still need to identify a “pharmaceutical partner interested in developing the antibodies commercially.” Naturally, that could take time.

Still, as the population of people living with HIV grows—currently, the US Centers for Disease Control and Prevention (CDC) estimates that there are more than 1.1 million Americans living with the virus—innovations that show promise in maintaining overall health are welcome news.

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous health care-related publications. He is the former editor of Infectious Disease Special Edition.