Viral and Host Mediators of Non-Suppressible HIV-1 Viremia

Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over...

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Published inmedRxiv : the preprint server for health sciences
Main Authors Mohammadi, Abbas, Etemad, Behzad, Zhang, Xin, Li, Yijia, Bedwell, Gregory J, Sharaf, Radwa, Kittilson, Autumn, Melberg, Meghan, Wong, Colline, Fajnzylber, Jesse, Worrall, Daniel P, Rosenthal, Alex, Jordan, Hannah, Jilg, Nikolaus, Kaseke, Clarety, Giguel, Francoise, Lian, Xiaodong, Deo, Rinki, Gillespie, Elisabeth, Chishti, Rida, Abrha, Sara, Adams, Taylor, Siagian, Abigail, Anderson, Peter L, Deeks, Steven G, Lederman, Michael M, Yawetz, Sigal, Kuritzkes, Daniel R, Lichterfeld, Mathias D, Tsibris, Athe, Carrington, Mary, Brumme, Zabrina L, Castillo-Mancilla, Jose R, Engelman, Alan N, Gaiha, Gaurav D, Li, Jonathan Z
Format Journal Article
LanguageEnglish
Published United States 31.03.2023
Subjects
CD8 immune response
HIV
integration
non-suppressible viremia
persistent low-level viremia
producer provirus
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Summary:Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over time. We defined proviruses that contribute to plasma viremia as "producer", and those that did not as "non-producer". Compared to ART-suppressed individuals, NSV participants had a significantly larger producer reservoir. Producer proviruses were enriched in chromosome 19 and in proximity to the activating H3K36me3 epigenetic mark. CD4 cells from NSV participants demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, NSV participants showed no elevation in HIV-specific CD8 cell responses and producer proviruses were enriched for HLA escape mutations. We identified critical host and viral mediators of NSV that represent potential targets to disrupt HIV persistence and promote viral silencing.