A small group of people living with HIV sensitive to two potent anti-HIV broadly neutralizing antibodies (bNAbs)—3BNC117 and 10-1074—tolerated multiple infusions of the antibodies and suppressed HIV for more than 15 weeks after stopping antiretroviral therapy (ART). The new findings, from a pilot clinical trial supported by the National Institutes of Health (NIH), the Bill & Melinda Gates Foundation and others, are reported today in Nature.
“A safe, reliable, antibody-based treatment regimen would open new possibilities for people living with HIV,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of NIH. “This study represents an important, early step towards that goal and, importantly, helps establish that a combination of broadly neutralizing antibodies to HIV can safely suppress the virus in certain individuals without the apparent development of viral resistance.”
Rockefeller University investigators and their colleagues recruited 15 volunteers whose HIV was suppressed with ART and was initially found to be sensitive to both 3BNC117 and 10-1074. Participants received infusions of both bNAbs, stopped taking ART two days later, and received additional infusions three and six weeks later.
In previous studies, researchers found that infusions of a single bNAb did not suppress HIV because resistant strains developed in some individuals. The new study tested the theory thata combination of multiple antibodies targeting distinct regions of HIV would both suppress the virus and prevent the development of resistance.
Among the 11 people who completed the study, nine maintained viral suppression without ART for an average of 15 weeks, until the amount of bNAbs in their bodies fell below protective levels. Two of the nine participants maintained virologic control through the end of the 30-week study follow-up period. The other two participants were found to harbor HIV resistant to at least one bNAb and experienced viral rebound before 12 weeks after stopping ART.
Overall, the findings suggest that like combination ART, combination bNAb infusions may be able to suppress HIV if the antibodies are maintained at therapeutic levels in people who do not harbor resistant virus. Further research is needed to identify bNAb combinations that can suppress HIV long-term in people whose HIV sensitivity to bNAbs is unknown. The Rockefeller University team currently is enrolling people living with HIV in a larger study to evaluate an optimized regimen of 3BNC117 and 10-1074. Learn more about the study reported in Nature by visiting ClinicalTrials.gov using study identifier NCT02825797, and learn more about the currently enrolling study under identifier NCT03526848.
Reference: P Mendoza et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature DOI: 10.1038/s41586-018-0531-2 (2018).