TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption

• DOI: 10.1371/journal.ppat.1009339
• Publication Date: 2021-02-18T20:29:31Z
• Authors: Denise C. Hsu; Alexandra Schuetz; Rawiwan Imerbsin; Decha Silsorn; Amarendra Pegu; Dutsadee Inthawong; Jumpol Sopanaporn; Pornsuk Visudhiphan; Weerawan Chuenarom; Boot Keawboon; Wei Shi; Merlin L. Robb; John R. Mascola; Romas Geleziunas; Richard A. Koup; Dan H. Barouch; Nelson L. Michael; Sandhya Vasan
• Keywords: TLR7; Simian immunodeficiency virus

Toll-like receptor 7 (TLR7) agonist and PGT121 (broadly neutralizing antibody, bnAb) administration previously delayed viral rebound induced SHIV remission. We evaluated the impact of GS-986 (TLR7 agonist) dual bnAbs on after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated daily suppressive ART from Day 14 post inoculation. Active arm animals (n = 8) received GS-986, N6-LS plasma suppression, starting week 14. immune activation SHIV-specific T cell responses but not expression in all active animals. After interruption, median time to was 6 weeks 3 control (p 0.024). In this animal model, combination associated a modest delay rebound. This strategy should be further better understand underlying mechanisms for induction virus-specific