Association of low level viremia with inflammation and mortality in HIV-infected adults
Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear. The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants f...
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| description | Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.
The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.
HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p |
| doi_str_mv | 10.1371/journal.pone.0026320 |
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The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.
HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥ 10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.
HIV RNA ≥ 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0026320</identifier><identifier>PMID: 22073156</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adipose tissue ; Adult ; Adults ; AIDS ; Analysis ; Antiretroviral drugs ; Biology ; C-reactive protein ; C-Reactive Protein - metabolism ; CD4 antigen ; Coagulation ; Demographics ; Demography ; Female ; Fibrin ; Fibrinogen ; HIV ; HIV - genetics ; HIV infections ; HIV Infections - mortality ; HIV Infections - pathology ; HIV Infections - virology ; HIV patients ; Human immunodeficiency virus ; Humans ; Infection ; Inflammation ; Inflammation - pathology ; Inflammation - virology ; Interleukin 6 ; Interleukins ; Low level ; Male ; Medical research ; Medicine ; Middle Aged ; Mortality ; Ribonucleic acid ; RNA ; RNA, Viral - blood ; Statistical analysis ; Target detection ; Viremia</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e26320-e26320</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-1601841c9091aa62eca3ab54faf2db800ee0b123384d7e471fc706c246a525113</citedby><cites>FETCH-LOGICAL-c691t-1601841c9091aa62eca3ab54faf2db800ee0b123384d7e471fc706c246a525113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206804/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206804/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22073156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eastburn, Abigail</creatorcontrib><creatorcontrib>Scherzer, Rebecca</creatorcontrib><creatorcontrib>Zolopa, Andrew R</creatorcontrib><creatorcontrib>Benson, Constance</creatorcontrib><creatorcontrib>Tracy, Russell</creatorcontrib><creatorcontrib>Do, Tri</creatorcontrib><creatorcontrib>Bacchetti, Peter</creatorcontrib><creatorcontrib>Shlipak, Michael</creatorcontrib><creatorcontrib>Grunfeld, Carl</creatorcontrib><creatorcontrib>Tien, Phyllis C</creatorcontrib><title>Association of low level viremia with inflammation and mortality in HIV-infected adults</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.
The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.
HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥ 10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.
HIV RNA ≥ 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adipose tissue</subject><subject>Adult</subject><subject>Adults</subject><subject>AIDS</subject><subject>Analysis</subject><subject>Antiretroviral drugs</subject><subject>Biology</subject><subject>C-reactive protein</subject><subject>C-Reactive Protein - metabolism</subject><subject>CD4 antigen</subject><subject>Coagulation</subject><subject>Demographics</subject><subject>Demography</subject><subject>Female</subject><subject>Fibrin</subject><subject>Fibrinogen</subject><subject>HIV</subject><subject>HIV - genetics</subject><subject>HIV infections</subject><subject>HIV Infections - mortality</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - virology</subject><subject>HIV patients</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infection</subject><subject>Inflammation</subject><subject>Inflammation - pathology</subject><subject>Inflammation - virology</subject><subject>Interleukin 6</subject><subject>Interleukins</subject><subject>Low level</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Viral - blood</subject><subject>Statistical analysis</subject><subject>Target detection</subject><subject>Viremia</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYmPwDxBEQgJx0eKPxElvkKoJWKVJk_gYl9apfdK6cuJiOx3797g0mxq0C-SLWPZz3tc5582yl5RMKa_oh43rfQd2unUdTglhgjPyKDulM84mghH--Gh_kj0LYUNIyWshnmYnjJGK01KcZj_nIThlIBrX5a7JrbvJLe7Q5jvjsTWQ35i4zk3XWGjbAwadzlvnI1gTb9NVfrG4niQCVUSdg-5tDM-zJw3YgC-G71n24_On7-cXk8urL4vz-eVEiRmNEyoIrQuqZmRGAQRDBRyWZdFAw_SyJgSRLCnjvC50hUVFG1URoVghoGQlpfwse33Q3VoX5NCTICmnRJR71UQsDoR2sJFbb1rwt9KBkX8PnF9J8NEoi1IjipqVWOo6eSmdTEHUlaC84TVdYtL6OLj1yxa1wi56sCPR8U1n1nLldjLNRtSkSALvBgHvfvUYomxNUGgtdOj6IGeEi2RXVol88w_58M8N1ArS-9MMXLJVe005LypRCy6ISNT0ASotnSasUn4ak85HBe9HBYmJ-DuuoA9BLr59_X_26nrMvj1i1wg2roOz_T5WYQwWB1B5F4LH5r7HlMh9_O-6Iffxl0P8U9mr4_ncF93lnf8BtBX-_A</recordid><startdate>20111102</startdate><enddate>20111102</enddate><creator>Eastburn, Abigail</creator><creator>Scherzer, Rebecca</creator><creator>Zolopa, Andrew R</creator><creator>Benson, Constance</creator><creator>Tracy, Russell</creator><creator>Do, Tri</creator><creator>Bacchetti, Peter</creator><creator>Shlipak, Michael</creator><creator>Grunfeld, Carl</creator><creator>Tien, Phyllis C</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111102</creationdate><title>Association of low level viremia with inflammation and mortality in HIV-infected adults</title><author>Eastburn, Abigail ; Scherzer, Rebecca ; Zolopa, Andrew R ; Benson, Constance ; Tracy, Russell ; Do, Tri ; Bacchetti, Peter ; Shlipak, Michael ; Grunfeld, Carl ; Tien, Phyllis C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-1601841c9091aa62eca3ab54faf2db800ee0b123384d7e471fc706c246a525113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adipose tissue</topic><topic>Adult</topic><topic>Adults</topic><topic>AIDS</topic><topic>Analysis</topic><topic>Antiretroviral drugs</topic><topic>Biology</topic><topic>C-reactive protein</topic><topic>C-Reactive Protein - metabolism</topic><topic>CD4 antigen</topic><topic>Coagulation</topic><topic>Demographics</topic><topic>Demography</topic><topic>Female</topic><topic>Fibrin</topic><topic>Fibrinogen</topic><topic>HIV</topic><topic>HIV - genetics</topic><topic>HIV infections</topic><topic>HIV Infections - mortality</topic><topic>HIV Infections - pathology</topic><topic>HIV Infections - virology</topic><topic>HIV patients</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infection</topic><topic>Inflammation</topic><topic>Inflammation - pathology</topic><topic>Inflammation - virology</topic><topic>Interleukin 6</topic><topic>Interleukins</topic><topic>Low level</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Viral - blood</topic><topic>Statistical analysis</topic><topic>Target detection</topic><topic>Viremia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eastburn, Abigail</creatorcontrib><creatorcontrib>Scherzer, Rebecca</creatorcontrib><creatorcontrib>Zolopa, Andrew R</creatorcontrib><creatorcontrib>Benson, Constance</creatorcontrib><creatorcontrib>Tracy, Russell</creatorcontrib><creatorcontrib>Do, Tri</creatorcontrib><creatorcontrib>Bacchetti, Peter</creatorcontrib><creatorcontrib>Shlipak, Michael</creatorcontrib><creatorcontrib>Grunfeld, Carl</creatorcontrib><creatorcontrib>Tien, Phyllis C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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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>Eastburn, Abigail</au><au>Scherzer, Rebecca</au><au>Zolopa, Andrew R</au><au>Benson, Constance</au><au>Tracy, Russell</au><au>Do, Tri</au><au>Bacchetti, Peter</au><au>Shlipak, Michael</au><au>Grunfeld, Carl</au><au>Tien, Phyllis C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of low level viremia with inflammation and mortality in HIV-infected adults</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-02</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e26320</spage><epage>e26320</epage><pages>e26320-e26320</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.
The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.
HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥ 10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.
HIV RNA ≥ 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22073156</pmid><doi>10.1371/journal.pone.0026320</doi><tpages>e26320</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
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| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acquired immune deficiency syndrome Adipose tissue Adult Adults AIDS Analysis Antiretroviral drugs Biology C-reactive protein C-Reactive Protein - metabolism CD4 antigen Coagulation Demographics Demography Female Fibrin Fibrinogen HIV HIV - genetics HIV infections HIV Infections - mortality HIV Infections - pathology HIV Infections - virology HIV patients Human immunodeficiency virus Humans Infection Inflammation Inflammation - pathology Inflammation - virology Interleukin 6 Interleukins Low level Male Medical research Medicine Middle Aged Mortality Ribonucleic acid RNA RNA, Viral - blood Statistical analysis Target detection Viremia |
| title | Association of low level viremia with inflammation and mortality in HIV-infected adults |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T00%3A04%3A42IST&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=Association%20of%20low%20level%20viremia%20with%20inflammation%20and%20mortality%20in%20HIV-infected%20adults&rft.jtitle=PloS%20one&rft.au=Eastburn,%20Abigail&rft.date=2011-11-02&rft.volume=6&rft.issue=11&rft.spage=e26320&rft.epage=e26320&rft.pages=e26320-e26320&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0026320&rft_dat=%3Cgale_plos_%3EA476863606%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1310659091&rft_id=info:pmid/22073156&rft_galeid=A476863606&rft_doaj_id=oai_doaj_org_article_dee6825e5d8e47cd84da687613f381be&rfr_iscdi=true |