Potent Anti-Viral Activity of a Trispecific HIV Antibody in SHIV-Infected Monkeys

Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combination bNAb therapy. Here a trispecific bNAb is shown to reduce viremia 100- to 1000-fold in viremic SHIV-infected macaques. After treatment discontinuation, viremia rebounded transiently and returned to low levels, through CD8-mediated immune control. These viruses remained sensitive to the trispecific despite loss of sensitivity to one of the parental bNAbs. Similarly, the trispecific bNAb suppressed the emergence of resistance in viruses derived from HIV-1 infected subjects, in contrast to parental bNAbs. Trispecific HIV-1 antibodies therefore mediates potent antiviral activity in vivo that minimizes the potential for immune escape.