Your browser doesn't support javascript.
loading
Viral and host mediators of non-suppressible HIV-1 viremia.
Mohammadi, Abbas; Etemad, Behzad; Zhang, Xin; Li, Yijia; Bedwell, Gregory J; Sharaf, Radwa; Kittilson, Autumn; Melberg, Meghan; Crain, Charles R; Traunbauer, Anna K; 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; Dorazio, Dominic; Anderson, Peter L; Deeks, Steven G; Lederman, Michael M; Yawetz, Sigal; Kuritzkes, Daniel R; Lichterfeld, Mathias D; Sieg, Scott; Tsibris, Athe; Carrington, Mary; Brumme, Zabrina L; Castillo-Mancilla, Jose R; Engelman, Alan N; Gaiha, Gaurav D; Li, Jonathan Z.
Afiliação
  • Mohammadi A; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Etemad B; Valley Health System, Las Vegas, NV, USA.
  • Zhang X; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Li Y; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Bedwell GJ; Beijing Friendship Hospital Pinggu Campus, Capital Medical University, Beijing, China.
  • Sharaf R; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kittilson A; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Melberg M; University of Pittsburgh, Pittsburgh, PA, USA.
  • Crain CR; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Traunbauer AK; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Wong C; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Fajnzylber J; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Worrall DP; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Rosenthal A; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Jordan H; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Jilg N; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kaseke C; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Giguel F; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Lian X; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Deo R; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Gillespie E; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Chishti R; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Abrha S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Adams T; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Siagian A; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Dorazio D; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Anderson PL; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Deeks SG; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Lederman MM; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Yawetz S; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kuritzkes DR; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Lichterfeld MD; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  • Sieg S; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Tsibris A; Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA.
  • Carrington M; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  • Brumme ZL; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Castillo-Mancilla JR; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Engelman AN; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Gaiha GD; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Li JZ; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Nat Med ; 29(12): 3212-3223, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37957382
Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as 'producer proviruses', and those that did not as 'non-producer proviruses'. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4+ T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8+ T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Soropositividade para HIV Limite: Female / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Soropositividade para HIV Limite: Female / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article