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Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2021 Oct; Vol. 192, pp. 114666. Date of Electronic Publication: 2021 Jun 26. - Publication Year :
- 2021
-
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.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Anti-Retroviral Agents adverse effects
Cross-Sectional Studies
Dasatinib adverse effects
Drug Therapy, Combination
Female
HIV Infections diagnosis
HIV-1 physiology
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive chemically induced
Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis
Male
Middle Aged
Protein Kinase Inhibitors administration & dosage
Protein Kinase Inhibitors adverse effects
Proviruses physiology
Reinfection diagnosis
Treatment Outcome
Anti-Retroviral Agents administration & dosage
Dasatinib administration & dosage
HIV Infections drug therapy
HIV-1 drug effects
Proviruses drug effects
Reinfection prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 192
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34186065
- Full Text :
- https://doi.org/10.1016/j.bcp.2021.114666