No change in HIV cellular burden and lower ADCC despite increased immune activation after combined immunotherapy with peg-IFN-α2b and two broadly neutralizing antibodies in suppressed HIV⁺ subjects

Background: Pegylated interferon α2b (peg-IFN-α2b) and the broadly neutralizing antibodies (bNabs) 3BNC117 and 10-1074 were individually shown to increase HIV suppression during antiretroviral therapy (ART) interruption (ATI). We evaluated the anti-HIV and immune effect of combined immunotherapy with peg-IFN-α2b+bNAbs in persons with HIV infection (PWH).

Methods: Peripheral blood mononuclear cells and plasma from 14 ART-suppressed PWH were assessed at baseline (ART), ART+4 weeks of peg-IFN-α2b, and ATI+26 weeks of peg-IFN-α2b+bNAbs immunotherapy for: 1) intact HIV DNA, 2) NK constitutive, and in vitro gp120 or IFN-α-induced antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cytotoxicity, and 3) immune activation.

Results: Immunotherapy did not alter cell-associated intact HIV DNA levels nor IFN-α-induced NK direct cytotoxicity. Yet, it decreased gp120-induced ADDC, and the percentage (%) of CD56^lo/+CD16⁺ on CD56⁺ while increasing the % of CD56^hi and CD56^lo/+CD16^- on CD56⁺ suggesting that decreased expression of CD16 (Fc receptor) on NK could result to lower ADCC. Immunotherapy also decreased CD57 expression on CD56^lo/+CD16⁺, while increased Tetherin, CD38, HLA-DR, NKp46, and CD169 on immune cells, and pro-inflammatory bisected GlcNAc glycans on bulk IgG.

Conclusion: Decreased ADCC and circulating CD16⁺ NK cell subsets despite increased immune activation may explain the lack of change in HIV cell burden after Peg-IFN-α2b+bNAbs administration in PWH.