Tags

Type your tag names separated by a space and hit enter

Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.
AIDS Res Hum Retroviruses. 2020 Aug 03 [Online ahead of print]AR

Abstract

The efficacy of combined antiretroviral therapy (cART) against HIV-1 is evidenced by reduction of plasma viremia, disease progression, viral transmission, and mortality. However, major challenges still remain in HIV-1 management, especially the emergence of resistant strains and the persistence of viral reservoirs, apparent after cART treatment interruption. Efforts are ongoing to explore the most effective means to intensify cART and successfully control residual viral replication. We anticipate that the reduction by cART of HIV-1 reservoirs could be further enhanced by combining cART with entry inhibitors and drugs that silence CCR5 expression. CCR5-targeting drugs are attractive option because of their low side effects when combined with other antiretroviral drugs. The concept that their inclusion would be effective has been supported by the reduction in two long terminal repeat unintegrated circular DNA, a marker for new infections, when CCR5-targeting drugs are added to standard antiretroviral treatment. This study is, in part, an extension of our previous study demonstrating greater preservation of human CD4+ T-cells and CD4+/CD8+ cell ratios in HIV-infected CD34+ NSG mice when CCR5-targeting drugs were included with standard cART. In this study, we treated HIV-1-infected cell cultures with cART or cART plus CCR5-targeting drugs (maraviroc and rapamycin). We found that treatment intensification with CCR5-targeting drugs led to a significant reduction of HIV-1 replication in peripheral blood ononuclear cells (PBMCs), as judged by measured viral DNA copies and p24 levels. Our data provide proof of principle for the benefit of adding CCR5-targeting drugs to traditional, standard cART to further lower viremia and subsequently reduce viral reservoirs in clinical settings, while potentially lowering side effects by reducing cART concentrations.

Authors+Show Affiliations

Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Biochemistry and Molecular Biology, and School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Biochemistry and Molecular Biology, and School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA. Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32623916

Citation

Weichseldorfer, Matthew, et al. "Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified By CCR5-Targeting Drugs." AIDS Research and Human Retroviruses, 2020.
Weichseldorfer M, Affram Y, Heredia A, et al. Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs. AIDS Res Hum Retroviruses. 2020.
Weichseldorfer, M., Affram, Y., Heredia, A., Tagaya, Y., Benedetti, F., Zella, D., Reitz, M., Romerio, F., & Latinovic, O. S. (2020). Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs. AIDS Research and Human Retroviruses. https://doi.org/10.1089/AID.2020.0064
Weichseldorfer M, et al. Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified By CCR5-Targeting Drugs. AIDS Res Hum Retroviruses. 2020 Aug 3; PubMed PMID: 32623916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs. AU - Weichseldorfer,Matthew, AU - Affram,Yvonne, AU - Heredia,Alonso, AU - Tagaya,Yutaka, AU - Benedetti,Francesca, AU - Zella,Davide, AU - Reitz,Marvin, AU - Romerio,Fabio, AU - Latinovic,Olga S, Y1 - 2020/08/03/ PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez KW - HIV/AIDS pathogenesis KW - antiretroviral therapies KW - coreceptor JF - AIDS research and human retroviruses JO - AIDS Res. Hum. Retroviruses N2 - The efficacy of combined antiretroviral therapy (cART) against HIV-1 is evidenced by reduction of plasma viremia, disease progression, viral transmission, and mortality. However, major challenges still remain in HIV-1 management, especially the emergence of resistant strains and the persistence of viral reservoirs, apparent after cART treatment interruption. Efforts are ongoing to explore the most effective means to intensify cART and successfully control residual viral replication. We anticipate that the reduction by cART of HIV-1 reservoirs could be further enhanced by combining cART with entry inhibitors and drugs that silence CCR5 expression. CCR5-targeting drugs are attractive option because of their low side effects when combined with other antiretroviral drugs. The concept that their inclusion would be effective has been supported by the reduction in two long terminal repeat unintegrated circular DNA, a marker for new infections, when CCR5-targeting drugs are added to standard antiretroviral treatment. This study is, in part, an extension of our previous study demonstrating greater preservation of human CD4+ T-cells and CD4+/CD8+ cell ratios in HIV-infected CD34+ NSG mice when CCR5-targeting drugs were included with standard cART. In this study, we treated HIV-1-infected cell cultures with cART or cART plus CCR5-targeting drugs (maraviroc and rapamycin). We found that treatment intensification with CCR5-targeting drugs led to a significant reduction of HIV-1 replication in peripheral blood ononuclear cells (PBMCs), as judged by measured viral DNA copies and p24 levels. Our data provide proof of principle for the benefit of adding CCR5-targeting drugs to traditional, standard cART to further lower viremia and subsequently reduce viral reservoirs in clinical settings, while potentially lowering side effects by reducing cART concentrations. SN - 1931-8405 UR - https://www.unboundmedicine.com/medline/citation/32623916/Anti-HIV_Activity_of_Standard_cART_in_Primary_Cells_Is_Intensified_by_CCR5-Targeting_Drugs L2 - https://www.liebertpub.com/doi/10.1089/AID.2020.0064?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.