No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy
Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2012-03, Vol.59 (3), p.229-235 |
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| container_title | Journal of acquired immune deficiency syndromes (1999) |
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| creator | GANDHI, Rajesh T COOMBS, Robert W WIEGAND, Ann KEARNEY, Mary JACOBSON, Jeffrey M D'AQUILA, Richard LEDERMAN, Michael M MELLORS, John W ERON, Joseph J CHAN, Ellen S BOSCH, Ronald J LU ZHENG MARGOLIS, David M READ, Sarah KALLUNGAL, Beatrice MING CHANG GOECKER, Erin A |
| description | Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.
We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA |
| doi_str_mv | 10.1097/QAI.0b013e31823fd1f2 |
| format | Article |
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We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.
Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.
In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0b013e31823fd1f2</identifier><identifier>PMID: 22083073</identifier><identifier>CODEN: JDSRET</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Anti-HIV Agents - administration & dosage ; Antiretroviral drugs ; Biological and medical sciences ; CD4 Lymphocyte Count ; Deoxyribonucleic acid ; DNA ; DNA, Viral - blood ; DNA, Viral - chemistry ; DNA, Viral - genetics ; Drug therapy ; Fundamental and applied biological sciences. Psychology ; HIV ; HIV Infections - blood ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - virology ; HIV Long Terminal Repeat - drug effects ; HIV-1 - genetics ; HIV-1 - physiology ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Indexing in process ; Infectious diseases ; Lymphocyte Activation - drug effects ; Medical sciences ; Microbiology ; Miscellaneous ; Polymerase Chain Reaction ; Pyrrolidinones - administration & dosage ; Raltegravir Potassium ; RNA, Viral - blood ; RNA, Viral - genetics ; T cell receptors ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viremia - blood ; Viremia - drug therapy ; Viremia - immunology ; Viremia - virology ; Virology ; Virus Replication - drug effects</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2012-03, Vol.59 (3), p.229-235</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright Lippincott Williams & Wilkins Mar 1, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-79a7637a7b6d90391e0e1bbdc50209e660338e4ef114253bcebaef25a039d8503</citedby><cites>FETCH-LOGICAL-c497t-79a7637a7b6d90391e0e1bbdc50209e660338e4ef114253bcebaef25a039d8503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25638249$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22083073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GANDHI, Rajesh T</creatorcontrib><creatorcontrib>COOMBS, Robert W</creatorcontrib><creatorcontrib>WIEGAND, Ann</creatorcontrib><creatorcontrib>KEARNEY, Mary</creatorcontrib><creatorcontrib>JACOBSON, Jeffrey M</creatorcontrib><creatorcontrib>D'AQUILA, Richard</creatorcontrib><creatorcontrib>LEDERMAN, Michael M</creatorcontrib><creatorcontrib>MELLORS, John W</creatorcontrib><creatorcontrib>ERON, Joseph J</creatorcontrib><creatorcontrib>CHAN, Ellen S</creatorcontrib><creatorcontrib>BOSCH, Ronald J</creatorcontrib><creatorcontrib>LU ZHENG</creatorcontrib><creatorcontrib>MARGOLIS, David M</creatorcontrib><creatorcontrib>READ, Sarah</creatorcontrib><creatorcontrib>KALLUNGAL, Beatrice</creatorcontrib><creatorcontrib>MING CHANG</creatorcontrib><creatorcontrib>GOECKER, Erin A</creatorcontrib><creatorcontrib>AIDS Clinical Trials Group (ACTG) A5244 Team</creatorcontrib><title>No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.
We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.
Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.
In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.</description><subject>Anti-HIV Agents - administration & dosage</subject><subject>Antiretroviral drugs</subject><subject>Biological and medical sciences</subject><subject>CD4 Lymphocyte Count</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Viral - blood</subject><subject>DNA, Viral - chemistry</subject><subject>DNA, Viral - genetics</subject><subject>Drug therapy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HIV</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV Long Terminal Repeat - drug effects</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Indexing in process</subject><subject>Infectious diseases</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Polymerase Chain Reaction</subject><subject>Pyrrolidinones - administration & dosage</subject><subject>Raltegravir Potassium</subject><subject>RNA, Viral - blood</subject><subject>RNA, Viral - genetics</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viremia - blood</subject><subject>Viremia - drug therapy</subject><subject>Viremia - immunology</subject><subject>Viremia - virology</subject><subject>Virology</subject><subject>Virus Replication - drug effects</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkW1rFDEUhQdRbK3-A5EgCH6ZmreZSb4Ia2ntQH0rtV9DJnOzmzqbbJPsQv9Ef7NZu61aCCTcPOdwLqeqXhN8SLDsPvyY9Yd4wIQBI4IyOxJLn1T7RHJed0Lwp-Xd0KbmhDV71YuUrjAmLefyebVHKRYMd2y_uv0a0LG1YDIKFp3rKcM86o2LqPcZfHLWGZ1d8KicSxf1hM5hNd0Pv-j4C2JCzqO8APRpCmHcGp32lzWpe781hhF9LzT4nIrWgNs4P0czn12EHMPmj-nFAqJe3bysnlk9JXi1uw-qnyfHF0en9dm3z_3R7Kw2XHa57qTuWtbpbmhHiZkkgIEMw2gaTLGEtsWMCeBgCeG0YYOBQYOljS7sKBrMDqqPd76r9bCE0ZRwJYVaRbfU8UYF7dT_P94t1DxsFOOUYUmKwfudQQzXa0hZLV0yME3aQ1gnRTAWggnWsIK-fYRehXX0ZT0lactx2zBeIH4HmRhSimAfshCstn2r0rd63HeRvfl3jwfRfcEFeLcDdDJ6slF749JfrmmZoFyy3wiutmw</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>GANDHI, Rajesh T</creator><creator>COOMBS, Robert W</creator><creator>WIEGAND, Ann</creator><creator>KEARNEY, Mary</creator><creator>JACOBSON, Jeffrey M</creator><creator>D'AQUILA, Richard</creator><creator>LEDERMAN, Michael M</creator><creator>MELLORS, John W</creator><creator>ERON, Joseph J</creator><creator>CHAN, Ellen S</creator><creator>BOSCH, Ronald J</creator><creator>LU ZHENG</creator><creator>MARGOLIS, David M</creator><creator>READ, Sarah</creator><creator>KALLUNGAL, Beatrice</creator><creator>MING CHANG</creator><creator>GOECKER, Erin A</creator><general>Lippincott Williams & Wilkins</general><general>Lippincott Williams & Wilkins Ovid Technologies</general><scope>IQODW</scope><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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>20120301</creationdate><title>No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy</title><author>GANDHI, Rajesh T ; COOMBS, Robert W ; WIEGAND, Ann ; KEARNEY, Mary ; JACOBSON, Jeffrey M ; D'AQUILA, Richard ; LEDERMAN, Michael M ; MELLORS, John W ; ERON, Joseph J ; CHAN, Ellen S ; BOSCH, Ronald J ; LU ZHENG ; MARGOLIS, David M ; READ, Sarah ; KALLUNGAL, Beatrice ; MING CHANG ; GOECKER, Erin A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-79a7637a7b6d90391e0e1bbdc50209e660338e4ef114253bcebaef25a039d8503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anti-HIV Agents - administration & dosage</topic><topic>Antiretroviral drugs</topic><topic>Biological and medical sciences</topic><topic>CD4 Lymphocyte Count</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Viral - blood</topic><topic>DNA, Viral - chemistry</topic><topic>DNA, Viral - genetics</topic><topic>Drug therapy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HIV</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - virology</topic><topic>HIV Long Terminal Repeat - drug effects</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Indexing in process</topic><topic>Infectious diseases</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Polymerase Chain Reaction</topic><topic>Pyrrolidinones - administration & dosage</topic><topic>Raltegravir Potassium</topic><topic>RNA, Viral - blood</topic><topic>RNA, Viral - genetics</topic><topic>T cell receptors</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viremia - blood</topic><topic>Viremia - drug therapy</topic><topic>Viremia - immunology</topic><topic>Viremia - virology</topic><topic>Virology</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GANDHI, Rajesh T</creatorcontrib><creatorcontrib>COOMBS, Robert W</creatorcontrib><creatorcontrib>WIEGAND, Ann</creatorcontrib><creatorcontrib>KEARNEY, Mary</creatorcontrib><creatorcontrib>JACOBSON, Jeffrey M</creatorcontrib><creatorcontrib>D'AQUILA, Richard</creatorcontrib><creatorcontrib>LEDERMAN, Michael M</creatorcontrib><creatorcontrib>MELLORS, John W</creatorcontrib><creatorcontrib>ERON, Joseph J</creatorcontrib><creatorcontrib>CHAN, Ellen S</creatorcontrib><creatorcontrib>BOSCH, Ronald J</creatorcontrib><creatorcontrib>LU ZHENG</creatorcontrib><creatorcontrib>MARGOLIS, David M</creatorcontrib><creatorcontrib>READ, Sarah</creatorcontrib><creatorcontrib>KALLUNGAL, Beatrice</creatorcontrib><creatorcontrib>MING CHANG</creatorcontrib><creatorcontrib>GOECKER, Erin A</creatorcontrib><creatorcontrib>AIDS Clinical Trials Group (ACTG) A5244 Team</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GANDHI, Rajesh T</au><au>COOMBS, Robert W</au><au>WIEGAND, Ann</au><au>KEARNEY, Mary</au><au>JACOBSON, Jeffrey M</au><au>D'AQUILA, Richard</au><au>LEDERMAN, Michael M</au><au>MELLORS, John W</au><au>ERON, Joseph J</au><au>CHAN, Ellen S</au><au>BOSCH, Ronald J</au><au>LU ZHENG</au><au>MARGOLIS, David M</au><au>READ, Sarah</au><au>KALLUNGAL, Beatrice</au><au>MING CHANG</au><au>GOECKER, Erin A</au><aucorp>AIDS Clinical Trials Group (ACTG) A5244 Team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>59</volume><issue>3</issue><spage>229</spage><epage>235</epage><pages>229-235</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><coden>JDSRET</coden><abstract>Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.
We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.
Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.
In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>22083073</pmid><doi>10.1097/QAI.0b013e31823fd1f2</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1525-4135 |
| ispartof | Journal of acquired immune deficiency syndromes (1999), 2012-03, Vol.59 (3), p.229-235 |
| issn | 1525-4135 1944-7884 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3423091 |
| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Open Access: Freely Accessible Journals by multiple vendors; Journals@Ovid Complete |
| subjects | Anti-HIV Agents - administration & dosage Antiretroviral drugs Biological and medical sciences CD4 Lymphocyte Count Deoxyribonucleic acid DNA DNA, Viral - blood DNA, Viral - chemistry DNA, Viral - genetics Drug therapy Fundamental and applied biological sciences. Psychology HIV HIV Infections - blood HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology HIV Long Terminal Repeat - drug effects HIV-1 - genetics HIV-1 - physiology Human immunodeficiency virus Human viral diseases Humans Indexing in process Infectious diseases Lymphocyte Activation - drug effects Medical sciences Microbiology Miscellaneous Polymerase Chain Reaction Pyrrolidinones - administration & dosage Raltegravir Potassium RNA, Viral - blood RNA, Viral - genetics T cell receptors T-Lymphocytes - drug effects T-Lymphocytes - immunology Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viremia - blood Viremia - drug therapy Viremia - immunology Viremia - virology Virology Virus Replication - drug effects |
| title | No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy |
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