Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1-Infected Treatment-Naive Subjects
OBJECTIVES:To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. METHODS:RCBL was determined using a modified Monogram PhenoSense HIV...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2009-03, Vol.50 (3), p.250-258, Article 250 |
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| container_title | Journal of acquired immune deficiency syndromes (1999) |
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| creator | Skowron, Gail Spritzler, John G Weidler, Jodi Robbins, Gregory K Johnson, Victoria A Chan, Ellen S Asmuth, David M Gandhi, Rajesh T Lie, Yolanda Bates, Michael Pollard, Richard B |
| description | OBJECTIVES:To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy.
METHODS:RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes.
RESULTS:Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = −0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = −0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL.
CONCLUSIONS:At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts. |
| doi_str_mv | 10.1097/QAI.0b013e3181938faf |
| format | Article |
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METHODS:RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes.
RESULTS:Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = −0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = −0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL.
CONCLUSIONS:At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.</description><identifier>ISSN: 1525-4135</identifier><identifier>ISSN: 0894-9255</identifier><identifier>EISSN: 1944-7884</identifier><identifier>EISSN: 2331-2289</identifier><identifier>DOI: 10.1097/QAI.0b013e3181938faf</identifier><identifier>PMID: 19194319</identifier><identifier>CODEN: JDSRET</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Acquired immune deficiency syndrome ; Adult ; Aged ; Antiretroviral drugs ; antiretroviral therapy ; Biological and medical sciences ; CD4 antigen ; CD4 Lymphocyte Count ; Cell activation ; Clinical trials ; Drug therapy ; Female ; Fundamental and applied biological sciences. Psychology ; HIV ; HIV Infections - virology ; HIV-1 - physiology ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Immunology ; Immunosuppressive agents ; Infectious diseases ; Male ; Medical research ; Medical sciences ; Memory cells ; Microbiology ; Middle Aged ; Miscellaneous ; Replication ; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains ; RNA ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral Load ; Virology ; Virus Replication</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2009-03, Vol.50 (3), p.250-258, Article 250</ispartof><rights>2009 Lippincott Williams & Wilkins, Inc.</rights><rights>2009 INIST-CNRS</rights><rights>Copyright Lippincott Williams & Wilkins Mar 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5392-9d92f525c8bf6e080f907a2427a047c2db3e6a0e62476bd48090327fb5a89d33</citedby><cites>FETCH-LOGICAL-c5392-9d92f525c8bf6e080f907a2427a047c2db3e6a0e62476bd48090327fb5a89d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00126334-200903010-00002$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>230,314,776,780,881,4595,27901,27902,65206</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21204938$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19194319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Skowron, Gail</creatorcontrib><creatorcontrib>Spritzler, John G</creatorcontrib><creatorcontrib>Weidler, Jodi</creatorcontrib><creatorcontrib>Robbins, Gregory K</creatorcontrib><creatorcontrib>Johnson, Victoria A</creatorcontrib><creatorcontrib>Chan, Ellen S</creatorcontrib><creatorcontrib>Asmuth, David M</creatorcontrib><creatorcontrib>Gandhi, Rajesh T</creatorcontrib><creatorcontrib>Lie, Yolanda</creatorcontrib><creatorcontrib>Bates, Michael</creatorcontrib><creatorcontrib>Pollard, Richard B</creatorcontrib><creatorcontrib>NIH/NIAID ACTG 384 Protocol Team and Monogram Biosciences</creatorcontrib><title>Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1-Infected Treatment-Naive Subjects</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>OBJECTIVES:To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy.
METHODS:RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes.
RESULTS:Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = −0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = −0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL.
CONCLUSIONS:At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adult</subject><subject>Aged</subject><subject>Antiretroviral drugs</subject><subject>antiretroviral therapy</subject><subject>Biological and medical sciences</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>Cell activation</subject><subject>Clinical trials</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HIV</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunosuppressive agents</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Memory cells</subject><subject>Microbiology</subject><subject>Middle Aged</subject><subject>Miscellaneous</subject><subject>Replication</subject><subject>Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains</subject><subject>RNA</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral Load</subject><subject>Virology</subject><subject>Virus Replication</subject><issn>1525-4135</issn><issn>0894-9255</issn><issn>1944-7884</issn><issn>2331-2289</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhiMEoqXwDxCKkOCWMv6IE3OoVK2ArlRRUVa9Wo4z6bo48dZOWvXf42WjAnupL_56Zvx63smytwSOCcjq04_T5TE0QBgyUhPJ6k53z7JDIjkvqrrmz9O6pGXBCSsPslcx3gAQwbl8mR0QmTBG5GF2e4kbZ40erR_yhd5oY8eH3A75Jbrd4ejzZd9Pg3f-2ppcD21-ZcO8u5hG43uM24iz5VVBiuXQoRmxzVcB9djjMBbftb3D_OfU3KSb-Dp70WkX8c08H2Wrr19Wi7Pi_OLbcnF6XpiSSVrIVtIu6Td10wmEGjoJlaacVhp4ZWjbMBQaUFBeiablNUhgtOqaUteyZewoO9ml3UxNj61JQoJ2ahNsr8OD8tqq_28Gu1bX_k4xXlMuZErwcU4Q_O2EcVS9jQad0wP6KSohpOAiVfcpkIIsBfA6ge_3wBs_hSEVQVHGRFkC3T7Ld5AJPsaA3aNkAmprvErGq33jU9i7f7_7N2h2OgEfZkBHo10X9GBsfOQoocBTrsR93ns_dcSfTkhVsu4pFbP4e-9GDPGXm-4xqDVqN65V6j8qGOMFha1ZQKCANCj7Dfym2qQ</recordid><startdate>200903</startdate><enddate>200903</enddate><creator>Skowron, Gail</creator><creator>Spritzler, John G</creator><creator>Weidler, Jodi</creator><creator>Robbins, Gregory K</creator><creator>Johnson, Victoria A</creator><creator>Chan, Ellen S</creator><creator>Asmuth, David M</creator><creator>Gandhi, Rajesh T</creator><creator>Lie, Yolanda</creator><creator>Bates, Michael</creator><creator>Pollard, Richard B</creator><general>Lippincott Williams & Wilkins, Inc</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>200903</creationdate><title>Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1-Infected Treatment-Naive Subjects</title><author>Skowron, Gail ; Spritzler, John G ; Weidler, Jodi ; Robbins, Gregory K ; Johnson, Victoria A ; Chan, Ellen S ; Asmuth, David M ; Gandhi, Rajesh T ; Lie, Yolanda ; Bates, Michael ; Pollard, Richard B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5392-9d92f525c8bf6e080f907a2427a047c2db3e6a0e62476bd48090327fb5a89d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adult</topic><topic>Aged</topic><topic>Antiretroviral drugs</topic><topic>antiretroviral therapy</topic><topic>Biological and medical sciences</topic><topic>CD4 antigen</topic><topic>CD4 Lymphocyte Count</topic><topic>Cell activation</topic><topic>Clinical trials</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HIV</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunosuppressive agents</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Memory cells</topic><topic>Microbiology</topic><topic>Middle Aged</topic><topic>Miscellaneous</topic><topic>Replication</topic><topic>Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains</topic><topic>RNA</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral Load</topic><topic>Virology</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Skowron, Gail</creatorcontrib><creatorcontrib>Spritzler, John G</creatorcontrib><creatorcontrib>Weidler, Jodi</creatorcontrib><creatorcontrib>Robbins, Gregory K</creatorcontrib><creatorcontrib>Johnson, Victoria A</creatorcontrib><creatorcontrib>Chan, Ellen S</creatorcontrib><creatorcontrib>Asmuth, David M</creatorcontrib><creatorcontrib>Gandhi, Rajesh T</creatorcontrib><creatorcontrib>Lie, Yolanda</creatorcontrib><creatorcontrib>Bates, Michael</creatorcontrib><creatorcontrib>Pollard, Richard B</creatorcontrib><creatorcontrib>NIH/NIAID ACTG 384 Protocol Team and Monogram Biosciences</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>MEDLINE - Academic</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>Skowron, Gail</au><au>Spritzler, John G</au><au>Weidler, Jodi</au><au>Robbins, Gregory K</au><au>Johnson, Victoria A</au><au>Chan, Ellen S</au><au>Asmuth, David M</au><au>Gandhi, Rajesh T</au><au>Lie, Yolanda</au><au>Bates, Michael</au><au>Pollard, Richard B</au><aucorp>NIH/NIAID ACTG 384 Protocol Team and Monogram Biosciences</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1-Infected Treatment-Naive Subjects</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2009-03</date><risdate>2009</risdate><volume>50</volume><issue>3</issue><spage>250</spage><epage>258</epage><pages>250-258</pages><artnum>250</artnum><issn>1525-4135</issn><issn>0894-9255</issn><eissn>1944-7884</eissn><eissn>2331-2289</eissn><coden>JDSRET</coden><abstract>OBJECTIVES:To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy.
METHODS:RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes.
RESULTS:Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = −0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = −0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL.
CONCLUSIONS:At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>19194319</pmid><doi>10.1097/QAI.0b013e3181938faf</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of acquired immune deficiency syndromes (1999), 2009-03, Vol.50 (3), p.250-258, Article 250 |
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| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free E- Journals; Journals@Ovid Complete |
| subjects | Acquired immune deficiency syndrome Adult Aged Antiretroviral drugs antiretroviral therapy Biological and medical sciences CD4 antigen CD4 Lymphocyte Count Cell activation Clinical trials Drug therapy Female Fundamental and applied biological sciences. Psychology HIV HIV Infections - virology HIV-1 - physiology Human immunodeficiency virus Human immunodeficiency virus 1 Human viral diseases Humans Immunology Immunosuppressive agents Infectious diseases Male Medical research Medical sciences Memory cells Microbiology Middle Aged Miscellaneous Replication Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains RNA Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load Virology Virus Replication |
| title | Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1-Infected Treatment-Naive Subjects |
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