Viral and host mediators of non-suppressible HIV-1 viremia

• DOI: 10.1038/s41591-023-02611-1
• Publication Date: 2023-11-13T17:02:08Z
• Authors: Abbas Mohammadi; Behzad Etemad; Xin Zhang; Yijia Li; Gregory J. Bedwell; Radwa Sharaf; Autumn Kittilson; Meghan Melberg; Charles R. Crain; Anna K. Traunbauer; Colline Wong; Jesse Fajnzylber; Daniel P. Worrall; Alex Rosenthal; Hannah Jordan; Nikolaus Jilg; Clarety Kaseke; Francoise Giguel; Xiaodong Lian; Rinki Deo; Elisabeth Gillespie; Rida Chishti; Sara Abrha; Taylor Adams; Abigail Siagian; Dominic Dorazio; Peter L. Anderson; Steven G. Deeks; Michael M. Lederman; Sigal Yawetz; Daniel R. Kuritzkes; Mathias D. Lichte...; Scott Sieg; Athe Tsibris; Mary Carrington; Zabrina L. Brumme; Jose R. Castillo-...; Alan N. Engelman; Gaurav D. Gaiha; Jonathan Z. Li
• Keywords: Viremia

Abstract Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with (88% male) and show that they are composed large clones viral evolution over time those longitudinal samples. We proviruses match RNA ‘producer proviruses’, did not ‘non-producer proviruses’. arose from expanded producer were significantly larger than genome-intact proviral reservoir ART-suppressed individuals. Integration sites enriched proximity to activating H3K36me3 epigenetic mark. CD4 + T cells participants demonstrated upregulation anti-apoptotic genes downregulation pro-apoptotic type I/II interferon-related pathways. Furthermore, showed lower HIV-specific CD8 cell responses compared untreated viremic controllers similar loads. identified potential critical host mediators may represent targets disrupt