Title

OAA04-Finding our way: Examining new approaches for cure

Code

OAA04

Session Type

On-demand oral abstract session

Track

Track A: Basic science

Channel

On-demand Abstracts

Presentations
Rapporteur Summary

0 min	The circadian clock machinery regulates HIV transcription in CD4+ T cells Christ-Dominique NGASSAKI-YOKA, Canada	Abstract

0 min	RNA-directed gene therapy protects CD4+ T cells during HIV challenge and delays virus rebound post-ART in humanized mice Chantelle AHLENSTIEL, University of New South Wales, Australia	Abstract

0 min	The balance of mucosal CD4 T cells prior to infection is associated with control of virus replication after therapeutic vaccination in SIV-infected rhesus macaques Hillary TUNGGAL, University of Washington, United States	Abstract

0 min	Early antiretroviral therapy favors post-treatment SIV control, which is associated with enhanced CD8+ T-cell antiviral activity against rebounding virus – the pVISCONTI study Caroline PASSAES, Institut Pasteur, France	Abstract

0 min	Evaluation of HIV-1 reservoir size and broadly neutralizing antibody (bNAb) susceptibility in individuals who initiated ART during acute and chronic infection Brian MOLDT, Gilead Sciences, Inc, United States	Abstract

AUTHOR

Philippe Rascle

SUMMARY

This session investigates new approaches to solve the viral persistence in HIV disease. The authors provide data about ART interruption (ATI) and the post-treatment controller (PTC) protocol to induce these characteristics in SIV infected monkeys. But they also studied new potential therapeutic targets to reduce HIV replication.

HIGHLIGHTS

Caroline PASSAES showed that an early ART initiation (4 weeks versus 24 weeks post-infection) in SIVmac infection favored a delayed viral rebound. Moreover, an early ART in SIV infection also favors lower viral setpoint post-ATI. She noticed a robust secondary SIV-specific CD8+ T cell response in PTC from lymphoid tissues. Brian MOLDT presented that ART initiation in PWH at Fiebig I-IV stage would be optimal to proof-of-concept HIV cure trials due to lower level of viral reservoir measured by total HIV DNA, low viral reservoir diversity and high susceptibility to bNAbs compared to chronic ART initiation in PWH. Chantelle AHLENSTIEL exposed humanized mice with PromA silencing (shPromA) cells (block HIV transcription) and CCR5 silencing (shCCR5) cells (block the viral entry). She demonstrated that CD4+ T cells were stable in HIV chronic infection with ART or ATI, for shPromA+shCCR5 mice. She showed a delay in viral rebound in shPromA and shPromA+shCCR5 mice. Hillary TUNGGAL exposed that the increase of CD4+ T cells and low Th17/Treg ratio pre-infection were associated with improved ART responsiveness and lower ATI viral burden. Christ-Dominique NGASSAKI-YOKA presented that REV-ERB agonism (SR9011) decreases IL-17 production in CD4+ T cells and in vitro HIV replication via BMAL1 inhibition.

CRITICAL ASSESSMENT

This session displays a lot of methodologies to induce PTC in SIV infection and reduce the viral production. The viral reservoir eradication still an important challenge in HIV disease. The PTC from SIV infection contribute to study the origin of plasma viremia control without ART. A multidisciplinary analysis on PTC could describe rapidly the special immune profile from these monkeys. Also, new therapeutic target could participate at the PTC induction via the reduction of HIV replication.