Multiomic analysis of ART-interruption cohorts identifies cell-extrinsic and -intrinsic mechanisms driving lymphocyte-mediated control of HIV rebound

The immunological mechanisms regulating HIV rebound after antiretroviral therapy (ART) interruption remain unclear. We examined relationships between host factors, HIV reservoir, and HIV time-to-rebound after analytical treatment interruption (ATI) by characterizing pre-ATI peripheral blood mononuclear cells (PBMCs) from 75 ART-suppressed people with HIV (PWH) using high-parameter methods. Across interventional (CLEAR, TEACH, REDUC) and non-interventional (A5345) cohorts, delayed rebound was not associated with intact HIV. Cohort-specific immune effectors were associated with delayed rebound. RNA sequencing of CD4+ T cells from A5345 revealed that mTOR inhibitor DDIT4 and zinc finger protein ZNF254 were associated with delayed rebound. In vitro and in vivo studies demonstrated that DDIT4 and ZNF254 suppressed HIV expression. Metformin induced DDIT4 and suppressed HIV expression in primary cells and cells from ART-suppressed PWH, suggesting that this affordable diabetes drug could be rep..., , , # Cell extrinsic and intrinsic mechanisms of lymphocyte-mediated post-ART control of HIV

Contact:
Nadia Roan, PhD
Gladstone Institutes
University of California, San Francisco
[[e-mail]](mailto:[e-mail])
[[e-mail]](mailto:[e-mail])

Dates of collection:
3/23/19 – 1/16/23

Information about geographic location of data collection:
Original specimens were from individuals in Denmark enrolled in three trials (CLEAR, PMID 26423811; REACH PMID 30932955; and REDUC PMID 27658863) and individuals in USA enrolled in ACTG A5345 (PMID 38329130). CyTOF datasets were generated in San Francisco, California, USA.

## Data and File Overview

Included are standard flow cytometry (FCS) files generated from clinical trial specimens of people with HIV (PWH) suppressed on antiretroviral therapy (ART) who underwent analytical treatment interruption (ATI). All specimens were obtained before analytical treatment interruption, and the primary associ..., We have received consent from participants to published the de-identified CyTOF data in the public domain. Each participant specimen was given an ID number that cannot be traced back to the individual.