Vigon, Lorena, Martinez-Roman, Paula, Rodriguez-Mora, Sara, Torres, Montserrat, Puertas, Maria C., Mateos, Elena, Navarro, Antonio, Sanchez-Conde, Matilde, Ambrosioni, Juan, Cervero, Miguel, Wyen, Christoph, Hoffmann, Christian, Miro, Jose M., Alcami, Jose, Podzamczer, Daniel, Garcia-Gutierrez, Valentin, Martinez-Picado, Javier ORCID: 0000-0002-4916-2129, Briz, Veronica ORCID: 0000-0003-2297-5098, Rosa Lopez-Huertas, Maria, Planelles, Vicente, Coiras, Mayte and Salgado, Maria ORCID: 0000-0003-1551-7216 (2021). Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy. Biochem. Pharmacol., 192. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 1873-2968

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Abstract

The latent viral reservoir formed by HIV-1, mainly in CD4 + T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4 + T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Vigon, LorenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Roman, PaulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Mora, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puertas, Maria C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mateos, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Navarro, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Conde, MatildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ambrosioni, JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cervero, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wyen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miro, Jose M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alcami, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Podzamczer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Gutierrez, ValentinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Picado, JavierUNSPECIFIEDorcid.org/0000-0002-4916-2129UNSPECIFIED
Briz, VeronicaUNSPECIFIEDorcid.org/0000-0003-2297-5098UNSPECIFIED
Rosa Lopez-Huertas, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Planelles, VicenteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coiras, MayteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salgado, MariaUNSPECIFIEDorcid.org/0000-0003-1551-7216UNSPECIFIED
URN: urn:nbn:de:hbz:38-602008
DOI: 10.1016/j.bcp.2021.114666
Journal or Publication Title: Biochem. Pharmacol.
Volume: 192
Date: 2021
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication: OXFORD
ISSN: 1873-2968
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; IMMUNODEFICIENCY-VIRUS-INFECTION; LONG-TERM SURVIVORS; ACUTE HIV-INFECTION; LATENT RESERVOIR; CLINICAL CHARACTERISTICS; SAMHD1 PHOSPHORYLATION; CYTOGENETIC RESPONSE; REPLICATIONMultiple languages
Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60200

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