Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.
Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants1,2. Combinations of drugs can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection3,4. Although anti-HIV-1 antibodies constitute a potential alternative to ART5,6, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants7-9. Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection10-12. Here we report on a phase 1b clinical trial ( NCT02825797 ) in which two potent bNAbs, 3BNC11713 and 10-107414, were administered in combination to seven HIV-1 viremic individuals. Infusions of 30 mg kg-1 of each of the antibodies were well-tolerated. In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log10 copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none of these individuals developed resistance to both antibodies. Larger studies will be necessary to confirm the efficacy of antibody combinations in reducing HIV-1 viremia and limiting the emergence of resistant viral variants.
Bar-On, Y, Gruell, H, Schoofs, T, Pai, JA, Nogueira, L, Butler, AL, Millard, K, Lehmann, C, Suárez, I, Oliveira, TY, Karagounis, T, Cohen, YZ, Wyen, C, Scholten, S, Handl, L, Belblidia, S, Dizon, JP, Vehreschild, JJ, Witmer-Pack, M, Shimeliovich, I, Jain, K, Fiddike, K, Seaton, KE, Yates, NL, Horowitz, J, Gulick, RM, Pfeifer, N, Tomaras, GD, Seaman, MS, Fätkenheuer, G, Caskey, M, Klein, F, and Nussenzweig, MC. "Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals." Nature Medicine 24, no. 11 (November 2018): 1701-1707.