PLoS Pathogens (Feb 2021)

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

  • 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

DOI
https://doi.org/10.1371/journal.ppat.1009339
Journal volume & issue
Vol. 17, no. 2
p. e1009339

Abstract

Read online

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