Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Hsu DC

PROVIDER: S-EPMC7924766 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hsu Denise C DC Schuetz Alexandra A Imerbsin Rawiwan R Silsorn Decha D Pegu Amarendra A Inthawong Dutsadee D Sopanaporn Jumpol J Visudhiphan Pornsuk P Chuenarom Weerawan W Keawboon Boot B Shi Wei W Robb Merlin L ML Mascola John R JR Geleziunas Romas R Koup Richard A RA Barouch Dan H DH Michael Nelson L NL Vasan Sandhya S

PLoS pathogens 20210218 2

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 suppre ...[more]

PMID: 33600506

Similar Datasets

Project description:The human immunodeficiency virus (HIV) reservoir is responsible for persistent viral infection, and a small number of mosaic latent cellular reservoirs promote viral rebound upon antiretroviral therapy interruption, which is the major obstacle to a cure. However, markers that determine effective therapy and viral rebound posttreatment interruption remain unclear. In this study, we comprehensively and longitudinally tracked dynamic decay of cell-associated viral RNA/DNA in systemic and lymphoid tissues in simian immunodeficiency virus (SIV)-infected rhesus macaques on prolonged combined antiretroviral therapy (cART) and evaluated predictors of viral rebound after treatment cessation. The results showed that suppressive ART substantially reduced plasma SIV RNA, cell-associated unspliced, and multiply spliced SIV RNA to undetectable levels, yet viral DNA remained detectable in systemic tissues and lymphoid compartments throughout cART. Intriguingly, a rapid increase of integrated proviral DNA in peripheral mononuclear cells was detected once treatment was withdrawn, accompanied by the emergence of detectable plasma viral load. Notably, the increase of peripheral proviral DNA after treatment interruption correlated with the emergence and degree of viral rebound. These findings suggest that measuring total viral DNA in SIV infection may be a relatively simple surrogate marker of reservoir size and may predict viral rebound after treatment interruption and inform treatment strategies.IMPORTANCE Viral reservoirs are involved in persistent HIV infection, and a small number of mosaic latent cellular reservoirs promote viral rebound upon analytical treatment interruption, which is the major obstacle to a cure. However, early indicators that can predict resurgence of viremia after treatment interruption may aid treatment decisions in people living with HIV. Utilizing the rhesus macaque model, we demonstrated that increased proviral DNA in peripheral cells after treatment interruption, rather than levels of proviral DNA, was a useful marker to predict the emergence and degree of viral rebound after treatment interruption, providing a rapid approach for monitoring HIV rebound and informing decisions.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets