Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

• Published in: Nature medicine Vol. 23; no. 2; pp. 185 - 191
• Main Authors: Caskey, Marina, Schoofs, Till, Gruell, Henning, Settler, Allison, Karagounis, Theodora, Kreider, Edward F, Murrell, Ben, Pfeifer, Nico, Nogueira, Lilian, Oliveira, Thiago Y, Learn, Gerald H, Cohen, Yehuda Z, Lehmann, Clara, Gillor, Daniel, Shimeliovich, Irina, Unson-O'Brien, Cecilia, Weiland, Daniela, Robles, Alexander, Kümmerle, Tim, Wyen, Christoph, Levin, Rebeka, Witmer-Pack, Maggi, Eren, Kemal, Ignacio, Caroline, Kiss, Szilard, West, Anthony P, Mouquet, Hugo, Zingman, Barry S, Gulick, Roy M, Keler, Tibor, Bjorkman, Pamela J, Seaman, Michael S, Hahn, Beatrice H, Fätkenheuer, Gerd, Schlesinger, Sarah J, Nussenzweig, Michel C, Klein, Florian
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2017; Nature Publishing Group
• Subjects: 631/154/51/1568; 692/699/249/1570/1901; Adult; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Neutralizing - administration & dosage; Antibodies, Neutralizing - pharmacology; Biomedicine; Cancer Research; Care and treatment; CD4 Lymphocyte Count; CHO Cells; Cricetulus; Development and progression; env Gene Products, Human Immunodeficiency Virus - genetics; Female; Genetic aspects; Health aspects; HIV; HIV Antibodies - administration & dosage; HIV Antibodies - pharmacology; HIV Envelope Protein gp120 - immunology; HIV infections; HIV Infections - blood; HIV Infections - drug therapy; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immunoglobulin G - administration & dosage; Immunoglobulin G - pharmacology; Infectious Diseases; Lentivirus; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Monoclonal antibodies; Neurosciences; Patient outcomes; Peptide Fragments - immunology; Pharmacology; Prevention; Recombinant Proteins; Retroviridae; RNA, Viral - blood; Safety; Viral Load; Viral proteins; Viremia - blood; Viremia - drug therapy; Virology; Young Adult
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.4268

Florian Klein and colleagues report that treating viremic HIV-1-infected individuals with the broadly neutralizing antibody 10-1074 reduced virus levels in blood, but antibody-resistant virus did emerge. Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log 10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping 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 might be useful for the treatment and prevention of HIV-1 infection.