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Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation.
Kincer, Laura P; Dravid, Ameet; Trunfio, Mattia; Calcagno, Andrea; Zhou, Shuntai; Vercesi, Riccardo; Spudich, Serena; Gisslen, Magnus; Price, Richard W; Cinque, Paola; Joseph, Sarah B.
Afiliação
  • Kincer LP; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Dravid A; Department of Medicine, Poona Hospital and Research Center, Pune, India.
  • Trunfio M; Ruby Hall Clinic, Pune, India.
  • Calcagno A; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy.
  • Zhou S; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy.
  • Vercesi R; ASL "CIttà di Torino," Torino, Italy.
  • Spudich S; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Gisslen M; Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
  • Price RW; Department of Neurology, Yale University, New Haven, Connecticut, USA.
  • Cinque P; Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Joseph SB; Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
J Clin Invest ; 134(19)2024 Oct 01.
Article em En | MEDLINE | ID: mdl-39352388
ABSTRACT
During antiretroviral therapy (ART), most people living with HIV-1 have undetectable HIV-1 RNA in their plasma. However, they occasionally present with new or progressive neurologic deficits and detectable HIV-1 RNA in the cerebrospinal fluid (CSF), a condition defined as neurosymptomatic HIV-1 CSF escape (NSE). We explored the source of neuropathogenesis and HIV-1 RNA in the CSF during NSE by characterizing HIV-1 populations and inflammatory biomarkers in CSF from 25 individuals with NSE. HIV-1 populations in the CSF were uniformly drug resistant and adapted to replication in CD4+ T cells, but differed greatly in genetic diversity, with some having low levels of diversity similar to those observed during untreated primary infection and others having high levels like those during untreated chronic infection. Higher diversity in the CSF during NSE was associated with greater CNS inflammation. Finally, optimization of ART regimen was associated with viral suppression and improvement of neurologic symptoms. These results are consistent with CNS inflammation and neurologic injury during NSE being driven by replication of partially drug-resistant virus in CNS CD4+ T cells. This is unlike nonsuppressible viremia in the plasma during ART, which typically lacks clinical consequences and is generated by virus expression without replication.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Replicação Viral / RNA Viral / Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Invest Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Replicação Viral / RNA Viral / Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Invest Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos