- May 12, 2026
- Nadia R. Roan, et al., Gladstone Institutes, UCSF
Topic/Product:
Immunology, Inflammation Panel 250
Disease Area:
HIV
Sample Type:
Plasma
Abstract
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, and 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 the 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 repurposed to silence HIV. Our results support the pursuit of both immune- and HIV-silencing strategies to achieve ART-free HIV remission.
Authors & Affiliations
Tongcui Ma¹˒²˒¹⁷, Ashley F. George¹˒²˒¹⁷, Zichong Li¹, Reuben Thomas¹, Kailin Yin¹˒², Min-Gyoung Shin¹, Mauricio Montano¹, Yusuke Matsui¹, Manickam Ashokkumar³, Kyrlia Young¹˒², Julia Prigann¹, Julie Frouard¹˒², Sabrina Leddy⁴, Maisha Adiba⁵, Christina Herrde⁵, Ulrike C. Lange⁵˒⁶, Cedric Feschotte⁴, Douglas F. Nixon⁷, Edward P. Browne³, Nancie M. Archin³, Jonathan Z. Li⁸, Davey Smith⁹, Steven Deeks², Ole S. Søgaard¹⁰, Martin Tolstrup¹⁰, Sulggi Lee², Satish K. Pillai²˒¹¹, Mohamed Abdel-Mohsen¹²˒¹³˒¹⁴, Katherine S. Pollard¹˒²˒¹⁵, Robert Siliciano¹⁶, Melanie Ott* ¹˒²˒¹⁵, Warner C. Greene* ¹˒², and Nadia R. Roan* ¹˒²˒¹⁸
¹ Gladstone Institutes, San Francisco, CA 94158, USA
² University of California, San Francisco, San Francisco, CA 94158, USA
³ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
⁴ Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA
⁵ Leibniz Institute of Virology, Hamburg, Germany
⁶ Institute of Infection Research and Vaccine Development, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
⁷ Institute of Translational Research, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
⁸ Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
⁹ School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
¹⁰ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
¹¹ Vitalant Research Institute, San Francisco, CA 94105, USA
¹² Division of Infectious Diseases, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
¹³ Center for Human Immunobiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
¹⁴ Potocsnak Longevity Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
¹⁵ Biohub, San Francisco, CA 94158, USA
¹⁶ Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
¹⁷ These authors contributed equally
¹⁸ Lead contact
