Env-specific antibodies promote post-treatment control in SIV-infected macaques

Viral latency reversal was observed in simian immunodeficiency virus (SIV)-infected rhesus macaques receiving antiretroviral therapy (ART), CD8α lymphocyte depletion and N-803 immunotherapy. However, this therapeutic approach did not reduce the viral reservoir size and treatment interruption resulted in rapid virus rebound. Here, to address this shortfall, we used four anti-SIV Env-specific rhesus IgG1 monoclonal antibodies (RhmAbs) that recognize unique targets on the SIV envelope. SIV mac239 -infected macaques were treated with ART only (group 1); ART + RhmAbs (group 2); or ART + RhmAbs + CD8α-depletion + N-803 (group 3). Robust latency reversal was only achieved in group 3. Viraemia rebounded in all macaques with similar kinetics after treatment interruption. However, compared with pre-ART viral loads, a greater fold reduction in rebound viraemia was seen in groups 2 and 3 and post-treatment control (PTC) required SIV RhmAbs. CD4 + T cells from macaques with PTC maintained low levels of intact SIV proviruses off ART and expressed increased interferon and decreased TGF-β signalling genes. This antiviral gene expression profile was also observed in CD4 + T cells with lower human immunodeficiency virus (HIV)-DNA content from ART-treated people with HIV. These results suggest that reduced virus production may contribute to PTC following ART interruption and provide a target for immune-based strategies to achieve durable viral control.