Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.
Identifieur interne : 000150 ( Main/Exploration ); précédent : 000149; suivant : 000151Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.
Auteurs : Matthew Weichseldorfer [États-Unis] ; Yvonne Affram [États-Unis] ; Alonso Heredia [États-Unis] ; Yutaka Tagaya [États-Unis] ; Francesca Benedetti [États-Unis] ; Davide Zella [États-Unis] ; Marvin Reitz [États-Unis] ; Fabio Romerio [États-Unis] ; Olga S. Latinovic [États-Unis]Source :
- AIDS research and human retroviruses [ 1931-8405 ] ; 2020.
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.
DOI: 10.1089/AID.2020.0064
PubMed: 32623916
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.</title><author><name sortKey="Weichseldorfer, Matthew" sort="Weichseldorfer, Matthew" uniqKey="Weichseldorfer M" first="Matthew" last="Weichseldorfer">Matthew Weichseldorfer</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Affram, Yvonne" sort="Affram, Yvonne" uniqKey="Affram Y" first="Yvonne" last="Affram">Yvonne Affram</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Heredia, Alonso" sort="Heredia, Alonso" uniqKey="Heredia A" first="Alonso" last="Heredia">Alonso Heredia</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Tagaya, Yutaka" sort="Tagaya, Yutaka" uniqKey="Tagaya Y" first="Yutaka" last="Tagaya">Yutaka Tagaya</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Benedetti, Francesca" sort="Benedetti, Francesca" uniqKey="Benedetti F" first="Francesca" last="Benedetti">Francesca Benedetti</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Zella, Davide" sort="Zella, Davide" uniqKey="Zella D" first="Davide" last="Zella">Davide Zella</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Reitz, Marvin" sort="Reitz, Marvin" uniqKey="Reitz M" first="Marvin" last="Reitz">Marvin Reitz</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Romerio, Fabio" sort="Romerio, Fabio" uniqKey="Romerio F" first="Fabio" last="Romerio">Fabio Romerio</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Latinovic, Olga S" sort="Latinovic, Olga S" uniqKey="Latinovic O" first="Olga S" last="Latinovic">Olga S. Latinovic</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32623916</idno><idno type="pmid">32623916</idno><idno type="doi">10.1089/AID.2020.0064</idno><idno type="wicri:Area/Main/Corpus">000050</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000050</idno><idno type="wicri:Area/Main/Curation">000050</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000050</idno><idno type="wicri:Area/Main/Exploration">000050</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.</title><author><name sortKey="Weichseldorfer, Matthew" sort="Weichseldorfer, Matthew" uniqKey="Weichseldorfer M" first="Matthew" last="Weichseldorfer">Matthew Weichseldorfer</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Affram, Yvonne" sort="Affram, Yvonne" uniqKey="Affram Y" first="Yvonne" last="Affram">Yvonne Affram</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Heredia, Alonso" sort="Heredia, Alonso" uniqKey="Heredia A" first="Alonso" last="Heredia">Alonso Heredia</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Tagaya, Yutaka" sort="Tagaya, Yutaka" uniqKey="Tagaya Y" first="Yutaka" last="Tagaya">Yutaka Tagaya</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Benedetti, Francesca" sort="Benedetti, Francesca" uniqKey="Benedetti F" first="Francesca" last="Benedetti">Francesca Benedetti</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Zella, Davide" sort="Zella, Davide" uniqKey="Zella D" first="Davide" last="Zella">Davide Zella</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Reitz, Marvin" sort="Reitz, Marvin" uniqKey="Reitz M" first="Marvin" last="Reitz">Marvin Reitz</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Romerio, Fabio" sort="Romerio, Fabio" uniqKey="Romerio F" first="Fabio" last="Romerio">Fabio Romerio</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Latinovic, Olga S" sort="Latinovic, Olga S" uniqKey="Latinovic O" first="Olga S" last="Latinovic">Olga S. Latinovic</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author></analytic><series><title level="j">AIDS research and human retroviruses</title><idno type="eISSN">1931-8405</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">32623916</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1931-8405</ISSN><JournalIssue CitedMedium="Internet"><Volume>36</Volume><Issue>10</Issue><PubDate><Year>2020</Year><Month>Oct</Month></PubDate></JournalIssue><Title>AIDS research and human retroviruses</Title><ISOAbbreviation>AIDS Res Hum Retroviruses</ISOAbbreviation></Journal><ArticleTitle>Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.</ArticleTitle><Pagination><MedlinePgn>835-841</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1089/AID.2020.0064</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Weichseldorfer</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Affram</LastName><ForeName>Yvonne</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heredia</LastName><ForeName>Alonso</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tagaya</LastName><ForeName>Yutaka</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benedetti</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zella</LastName><ForeName>Davide</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reitz</LastName><ForeName>Marvin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Romerio</LastName><ForeName>Fabio</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Latinovic</LastName><ForeName>Olga S</ForeName><Initials>OS</Initials><AffiliationInfo><Affiliation>Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>08</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>AIDS Res Hum Retroviruses</MedlineTA><NlmUniqueID>8709376</NlmUniqueID><ISSNLinking>0889-2229</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CitationSubset>X</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">HIV/AIDS pathogenesis</Keyword><Keyword MajorTopicYN="N">antiretroviral therapies</Keyword><Keyword MajorTopicYN="N">coreceptor</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>7</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>7</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32623916</ArticleId><ArticleId IdType="doi">10.1089/AID.2020.0064</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region><settlement><li>College Park (Maryland)</li></settlement><orgName><li>Université du Maryland</li></orgName></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Weichseldorfer, Matthew" sort="Weichseldorfer, Matthew" uniqKey="Weichseldorfer M" first="Matthew" last="Weichseldorfer">Matthew Weichseldorfer</name></region><name sortKey="Affram, Yvonne" sort="Affram, Yvonne" uniqKey="Affram Y" first="Yvonne" last="Affram">Yvonne Affram</name><name sortKey="Benedetti, Francesca" sort="Benedetti, Francesca" uniqKey="Benedetti F" first="Francesca" last="Benedetti">Francesca Benedetti</name><name sortKey="Benedetti, Francesca" sort="Benedetti, Francesca" uniqKey="Benedetti F" first="Francesca" last="Benedetti">Francesca Benedetti</name><name sortKey="Heredia, Alonso" sort="Heredia, Alonso" uniqKey="Heredia A" first="Alonso" last="Heredia">Alonso Heredia</name><name sortKey="Heredia, Alonso" sort="Heredia, Alonso" uniqKey="Heredia A" first="Alonso" last="Heredia">Alonso Heredia</name><name sortKey="Latinovic, Olga S" sort="Latinovic, Olga S" uniqKey="Latinovic O" first="Olga S" last="Latinovic">Olga S. Latinovic</name><name sortKey="Latinovic, Olga S" sort="Latinovic, Olga S" uniqKey="Latinovic O" first="Olga S" last="Latinovic">Olga S. Latinovic</name><name sortKey="Reitz, Marvin" sort="Reitz, Marvin" uniqKey="Reitz M" first="Marvin" last="Reitz">Marvin Reitz</name><name sortKey="Reitz, Marvin" sort="Reitz, Marvin" uniqKey="Reitz M" first="Marvin" last="Reitz">Marvin Reitz</name><name sortKey="Romerio, Fabio" sort="Romerio, Fabio" uniqKey="Romerio F" first="Fabio" last="Romerio">Fabio Romerio</name><name sortKey="Romerio, Fabio" sort="Romerio, Fabio" uniqKey="Romerio F" first="Fabio" last="Romerio">Fabio Romerio</name><name sortKey="Tagaya, Yutaka" sort="Tagaya, Yutaka" uniqKey="Tagaya Y" first="Yutaka" last="Tagaya">Yutaka Tagaya</name><name sortKey="Tagaya, Yutaka" sort="Tagaya, Yutaka" uniqKey="Tagaya Y" first="Yutaka" last="Tagaya">Yutaka Tagaya</name><name sortKey="Zella, Davide" sort="Zella, Davide" uniqKey="Zella D" first="Davide" last="Zella">Davide Zella</name><name sortKey="Zella, Davide" sort="Zella, Davide" uniqKey="Zella D" first="Davide" last="Zella">Davide Zella</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Bois/explor/RapamycinFungusV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000150 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000150 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Bois
|area= RapamycinFungusV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:32623916
|texte= Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32623916" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a RapamycinFungusV1
| This area was generated with Dilib version V0.6.38. |  |