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Human herpesvirus replication and abnormal CD8+ T cell activation and low CD4+ T cell counts in antiretroviral-suppressed HIV-infected patients
Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was assoc...
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| Published in: | PloS one 2009-04, Vol.4 (4), p.e5277-e5277 |
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| cites | cdi_FETCH-LOGICAL-c721t-f3945b6dfc7fed2f74a833f1b6c8e5c8b30088a58b4a66f746b1c88be3851c973 |
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| creator | Jacobson, Mark A Ditmer, Dirk P Sinclair, Elizabeth Martin, Jeffrey N Deeks, Steven G Hunt, Peter Mocarski, Edward S Shiboski, Caroline |
| description | Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated with higher virus-specific T cell activation and the failure to achieve normal absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral therapy.
Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA 10% and plateau absolute CD4+ T cell counts |
| doi_str_mv | 10.1371/journal.pone.0005277 |
| format | article |
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Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and KSHV DNA PCR assay. Eleven cases were chosen who had CD8+ T cell CD38+HLA-DR+ expression >10% and plateau absolute CD4+ T cell counts <500 cells/microL. Five controls from the same study had CD8+ T cell CD38 expression <10% and plateau absolute CD4+ T cell counts >500 cells/microL.
Among all subjects combined, 18% of PMBC samples were positive for CMV DNA, and 27%, 73% and 24% of saliva samples were positive for CMV, EBV and KSHV DNA, respectively. No significant differences or trends were observed between cases and controls in proportions of all CMV, EBV or KSHV DNA positive specimens, proportions of subjects in each group that intermittently or continuously shed CMV, EBV or KSHV DNA in saliva, or the median number of genome copies of CMV, EBV and KSHV DNA in saliva. Overall, number of genome copies in saliva were lower for KSHV than for CMV and lower for CMV than for EBV. Although replication of CMV, EBV and KSHV persists in many antiretroviral-suppressed, HIV-infected patients, we observed no evidence in this pilot case-control study that the magnitude of such human herpesvirus replication is associated with abnormally increased CD8+ T cell activation and sub-normal plateau absolute CD4+ T cell counts following virologically suppressive antiretroviral therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005277</identifier><identifier>PMID: 19381272</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adult ; AIDS ; Anti-HIV Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Antiviral agents ; Base Sequence ; Care and treatment ; CD38 antigen ; CD4 antigen ; CD4 Lymphocyte Count ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cell activation ; Cytomegalovirus ; Deoxyribonucleic acid ; DNA ; DNA Primers ; Epstein-Barr virus ; Female ; Genomes ; Herpes viruses ; Highly active antiretroviral therapy ; Histocompatibility antigen HLA ; HIV ; HIV (Viruses) ; HIV infection ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV patients ; Human cytomegalovirus ; Human herpesvirus ; Human immunodeficiency virus ; Humans ; Immunology/Immunomodulation ; Immunophenotyping ; Infectious Diseases/HIV Infection and AIDS ; Infectious Diseases/Viral Infections ; Kaposi's sarcoma ; Kaposi's sarcoma-associated herpesvirus ; Kaposis sarcoma ; Lymphocyte Activation ; Lymphocytes T ; Male ; Middle Aged ; Multiplexing ; Patients ; Peripheral blood mononuclear cells ; Polymerase Chain Reaction ; Replication ; Ribonucleic acid ; RNA ; Saliva ; Sarcoma ; Simplexvirus - physiology ; T cell receptors ; T cells ; Therapy ; Virus Replication ; Viruses</subject><ispartof>PloS one, 2009-04, Vol.4 (4), p.e5277-e5277</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Jacobson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Jacobson et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c721t-f3945b6dfc7fed2f74a833f1b6c8e5c8b30088a58b4a66f746b1c88be3851c973</citedby><cites>FETCH-LOGICAL-c721t-f3945b6dfc7fed2f74a833f1b6c8e5c8b30088a58b4a66f746b1c88be3851c973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1290652496/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1290652496?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19381272$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Unutmaz, Derya</contributor><creatorcontrib>Jacobson, Mark A</creatorcontrib><creatorcontrib>Ditmer, Dirk P</creatorcontrib><creatorcontrib>Sinclair, Elizabeth</creatorcontrib><creatorcontrib>Martin, Jeffrey N</creatorcontrib><creatorcontrib>Deeks, Steven G</creatorcontrib><creatorcontrib>Hunt, Peter</creatorcontrib><creatorcontrib>Mocarski, Edward S</creatorcontrib><creatorcontrib>Shiboski, Caroline</creatorcontrib><title>Human herpesvirus replication and abnormal CD8+ T cell activation and low CD4+ T cell counts in antiretroviral-suppressed HIV-infected patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated with higher virus-specific T cell activation and the failure to achieve normal absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral therapy.
Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and KSHV DNA PCR assay. Eleven cases were chosen who had CD8+ T cell CD38+HLA-DR+ expression >10% and plateau absolute CD4+ T cell counts <500 cells/microL. Five controls from the same study had CD8+ T cell CD38 expression <10% and plateau absolute CD4+ T cell counts >500 cells/microL.
Among all subjects combined, 18% of PMBC samples were positive for CMV DNA, and 27%, 73% and 24% of saliva samples were positive for CMV, EBV and KSHV DNA, respectively. No significant differences or trends were observed between cases and controls in proportions of all CMV, EBV or KSHV DNA positive specimens, proportions of subjects in each group that intermittently or continuously shed CMV, EBV or KSHV DNA in saliva, or the median number of genome copies of CMV, EBV and KSHV DNA in saliva. Overall, number of genome copies in saliva were lower for KSHV than for CMV and lower for CMV than for EBV. Although replication of CMV, EBV and KSHV persists in many antiretroviral-suppressed, HIV-infected patients, we observed no evidence in this pilot case-control study that the magnitude of such human herpesvirus replication is associated with abnormally increased CD8+ T cell activation and sub-normal plateau absolute CD4+ T cell counts following virologically suppressive antiretroviral therapy.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adult</subject><subject>AIDS</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Antiviral agents</subject><subject>Base Sequence</subject><subject>Care and treatment</subject><subject>CD38 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell activation</subject><subject>Cytomegalovirus</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Primers</subject><subject>Epstein-Barr virus</subject><subject>Female</subject><subject>Genomes</subject><subject>Herpes viruses</subject><subject>Highly active antiretroviral therapy</subject><subject>Histocompatibility antigen HLA</subject><subject>HIV</subject><subject>HIV (Viruses)</subject><subject>HIV infection</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV patients</subject><subject>Human cytomegalovirus</subject><subject>Human herpesvirus</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunology/Immunomodulation</subject><subject>Immunophenotyping</subject><subject>Infectious Diseases/HIV Infection and AIDS</subject><subject>Infectious Diseases/Viral Infections</subject><subject>Kaposi's sarcoma</subject><subject>Kaposi's sarcoma-associated herpesvirus</subject><subject>Kaposis sarcoma</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiplexing</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Polymerase Chain Reaction</subject><subject>Replication</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Saliva</subject><subject>Sarcoma</subject><subject>Simplexvirus - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jacobson, Mark A</au><au>Ditmer, Dirk P</au><au>Sinclair, Elizabeth</au><au>Martin, Jeffrey N</au><au>Deeks, Steven G</au><au>Hunt, Peter</au><au>Mocarski, Edward S</au><au>Shiboski, Caroline</au><au>Unutmaz, Derya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human herpesvirus replication and abnormal CD8+ T cell activation and low CD4+ T cell counts in antiretroviral-suppressed HIV-infected patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-04-17</date><risdate>2009</risdate><volume>4</volume><issue>4</issue><spage>e5277</spage><epage>e5277</epage><pages>e5277-e5277</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated with higher virus-specific T cell activation and the failure to achieve normal absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral therapy.
Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and KSHV DNA PCR assay. Eleven cases were chosen who had CD8+ T cell CD38+HLA-DR+ expression >10% and plateau absolute CD4+ T cell counts <500 cells/microL. Five controls from the same study had CD8+ T cell CD38 expression <10% and plateau absolute CD4+ T cell counts >500 cells/microL.
Among all subjects combined, 18% of PMBC samples were positive for CMV DNA, and 27%, 73% and 24% of saliva samples were positive for CMV, EBV and KSHV DNA, respectively. No significant differences or trends were observed between cases and controls in proportions of all CMV, EBV or KSHV DNA positive specimens, proportions of subjects in each group that intermittently or continuously shed CMV, EBV or KSHV DNA in saliva, or the median number of genome copies of CMV, EBV and KSHV DNA in saliva. Overall, number of genome copies in saliva were lower for KSHV than for CMV and lower for CMV than for EBV. Although replication of CMV, EBV and KSHV persists in many antiretroviral-suppressed, HIV-infected patients, we observed no evidence in this pilot case-control study that the magnitude of such human herpesvirus replication is associated with abnormally increased CD8+ T cell activation and sub-normal plateau absolute CD4+ T cell counts following virologically suppressive antiretroviral therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19381272</pmid><doi>10.1371/journal.pone.0005277</doi><tpages>e5277</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-04, Vol.4 (4), p.e5277-e5277 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1290652496 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | Acquired immune deficiency syndrome Adult AIDS Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Antiviral agents Base Sequence Care and treatment CD38 antigen CD4 antigen CD4 Lymphocyte Count CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell activation Cytomegalovirus Deoxyribonucleic acid DNA DNA Primers Epstein-Barr virus Female Genomes Herpes viruses Highly active antiretroviral therapy Histocompatibility antigen HLA HIV HIV (Viruses) HIV infection HIV Infections - drug therapy HIV Infections - immunology HIV patients Human cytomegalovirus Human herpesvirus Human immunodeficiency virus Humans Immunology/Immunomodulation Immunophenotyping Infectious Diseases/HIV Infection and AIDS Infectious Diseases/Viral Infections Kaposi's sarcoma Kaposi's sarcoma-associated herpesvirus Kaposis sarcoma Lymphocyte Activation Lymphocytes T Male Middle Aged Multiplexing Patients Peripheral blood mononuclear cells Polymerase Chain Reaction Replication Ribonucleic acid RNA Saliva Sarcoma Simplexvirus - physiology T cell receptors T cells Therapy Virus Replication Viruses |
| title | Human herpesvirus replication and abnormal CD8+ T cell activation and low CD4+ T cell counts in antiretroviral-suppressed HIV-infected patients |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T17%3A23%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20herpesvirus%20replication%20and%20abnormal%20CD8+%20T%20cell%20activation%20and%20low%20CD4+%20T%20cell%20counts%20in%20antiretroviral-suppressed%20HIV-infected%20patients&rft.jtitle=PloS%20one&rft.au=Jacobson,%20Mark%20A&rft.date=2009-04-17&rft.volume=4&rft.issue=4&rft.spage=e5277&rft.epage=e5277&rft.pages=e5277-e5277&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0005277&rft_dat=%3Cgale_plos_%3EA473224890%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c721t-f3945b6dfc7fed2f74a833f1b6c8e5c8b30088a58b4a66f746b1c88be3851c973%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1290652496&rft_id=info:pmid/19381272&rft_galeid=A473224890&rfr_iscdi=true |