Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity

Niessl, Julia; Baxter, Amy E.; Mendoza, Pilar; Jankovic, Mila; Cohen, Yehuda Z.; Butler, Allison L.; Lu, Ching-Lan; Dubé, Mathieu; Shimeliovich, Irina; Gruell, Henning; Klein, Florian; Caskey, Marina; Nussenzweig, Michel C.; Kaufmann, Daniel E.

Combination antiretroviral therapy (ART) is highly effective in controlling human immunodeficiency virus (HIV)-1 but requires lifelong medication due to the existence of a latent viral reservoir(1,2). Potent broadly neutralizing antibodies (bNAbs) represent a potential alternative or adjuvant to ART. In addition to suppressing viremia, bNAbs may have T cell immunomodulatory effects as seen for other forms of immunotherapy(3). However, this has not been established in individuals who are infected with HIV-1. Here, we document increased HIV-1 Gag-specific CD8(+) T cell responses in the peripheral blood of all nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving bNAb therapy during ART interruption(4). Increased CD4(+) T cell responses were detected in eight individuals. The increased T cell responses were due both to newly detectable reactivity to HIV-1 Gag epitopes and the expansion of pre-existing measurable responses. These data demonstrate that bNAb therapy during ART interruption is associated with enhanced HIV-1-specific T cell responses. Whether these augmented T cell responses can contribute to bNAb-mediated viral control remains to be determined.