Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated to date. Here we report on its safety and activity in 33 subjects who received a single intravenous infusion of the antibody. 10-1074 was well tolerated with a half-life of 24.0 days in uninfected and 12.8 days in HIV-1-infected subjects. 13 viremic subjects received the highest dose of 30 mg/kg 10-1074. 11 of these participants were 10-1074-sensitive and showed a rapid decline of viremia by a mean of 1.52 log10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses within the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting non-overlapping epitopes, such as the anti-CD4 binding site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite may be useful for treatment and prevention of HIV-1 infection.

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

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