Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients
To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints. Observational. Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+)...
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| Veröffentlicht in: | AIDS (London) 2010-07, Vol.24 (12), p.1877-1886 |
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| creator | ACHHRA, Amit C AMIN, Janaki LAW, Matthew G EMERY, Sean GERSTOFT, Jan CORDIN, Fred M VJECHA, Michael J NEATON, James D COOPER, David A |
| description | To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints.
Observational.
Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count.
Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope |
| doi_str_mv | 10.1097/qad.0b013e32833b1b26 |
| format | Article |
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Observational.
Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count.
Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03).
Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/qad.0b013e32833b1b26</identifier><identifier>PMID: 20588170</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Antiretroviral Therapy, Highly Active ; Biological and medical sciences ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - immunology ; Disease Progression ; Endpoint Determination ; Female ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - mortality ; HIV-1 - immunology ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunologic Deficiency Syndromes - drug therapy ; Immunologic Deficiency Syndromes - immunology ; Immunologic Deficiency Syndromes - mortality ; Immunopathology ; Infectious diseases ; Male ; Medical sciences ; Predictive Value of Tests ; Proportional Hazards Models ; Prospective Studies ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>AIDS (London), 2010-07, Vol.24 (12), p.1877-1886</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-ec279eaea97c8d69a1fba0af9d41260475e968d9f3f19db247d65f9a99fa91043</citedby><cites>FETCH-LOGICAL-c535t-ec279eaea97c8d69a1fba0af9d41260475e968d9f3f19db247d65f9a99fa91043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23088149$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20588170$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ACHHRA, Amit C</creatorcontrib><creatorcontrib>AMIN, Janaki</creatorcontrib><creatorcontrib>LAW, Matthew G</creatorcontrib><creatorcontrib>EMERY, Sean</creatorcontrib><creatorcontrib>GERSTOFT, Jan</creatorcontrib><creatorcontrib>CORDIN, Fred M</creatorcontrib><creatorcontrib>VJECHA, Michael J</creatorcontrib><creatorcontrib>NEATON, James D</creatorcontrib><creatorcontrib>COOPER, David A</creatorcontrib><creatorcontrib>INSIGHT ESPRIT & SILCAAT study groups</creatorcontrib><title>Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints.
Observational.
Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count.
Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03).
Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths.</description><subject>Adult</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Biological and medical sciences</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Disease Progression</subject><subject>Endpoint Determination</subject><subject>Female</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - mortality</subject><subject>HIV-1 - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunologic Deficiency Syndromes - drug therapy</subject><subject>Immunologic Deficiency Syndromes - immunology</subject><subject>Immunologic Deficiency Syndromes - mortality</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Predictive Value of Tests</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0269-9370</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuPFCEUhYnROO3oPzCGjXFVIxRQFBuTyfiYTiYxJuqW3OJho1XQA5Rm_r10ph0fG1cE-M65j4PQU0rOKFHy5TXYMzIRyhzrR8YmOvXDPbShXLJOCEnvow3pB9UpJskJelTKV0KIIOP4EJ30RIwjlWSD1u2yrDFZ54MJLpobDNHiunM4h_INJ4-LyyGtBZs5xGBgxi7afQqxFhwiBvzDzTMudbXBWWzSLuV6kNXsoLaXy-3nLkTvzOGyh9qK1PIYPfAwF_fkeJ6iT2_ffLy47K7ev9tenF91RjBRO2d6qRw4UNKMdlBA_QQEvLKc9gPhUjg1jFZ55qmyU8-lHYRXoJQHRQlnp-jVre9-nRZnTaudYdb7HBbINzpB0H__xLDTX9J33au2u0E1gxdHg5yuV1eqXkIxbWKIri1FSyEoZ4TJ_5OMKSn5ePDkt6TJqZTs_F0_lOhDtPrD-Wv9b7RN9uzPWe5Ev7JswPMjAKXl5DNEE8pvjrXsKVfsJ0qRsKk</recordid><startdate>20100731</startdate><enddate>20100731</enddate><creator>ACHHRA, Amit C</creator><creator>AMIN, Janaki</creator><creator>LAW, Matthew G</creator><creator>EMERY, Sean</creator><creator>GERSTOFT, Jan</creator><creator>CORDIN, Fred M</creator><creator>VJECHA, Michael J</creator><creator>NEATON, James D</creator><creator>COOPER, David A</creator><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>7T5</scope><scope>7U1</scope><scope>7U2</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20100731</creationdate><title>Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients</title><author>ACHHRA, Amit C ; AMIN, Janaki ; LAW, Matthew G ; EMERY, Sean ; GERSTOFT, Jan ; CORDIN, Fred M ; VJECHA, Michael J ; NEATON, James D ; COOPER, David A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-ec279eaea97c8d69a1fba0af9d41260475e968d9f3f19db247d65f9a99fa91043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Biological and medical sciences</topic><topic>CD4 Lymphocyte Count</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Disease Progression</topic><topic>Endpoint Determination</topic><topic>Female</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - mortality</topic><topic>HIV-1 - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunologic Deficiency Syndromes - drug therapy</topic><topic>Immunologic Deficiency Syndromes - immunology</topic><topic>Immunologic Deficiency Syndromes - mortality</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Predictive Value of Tests</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ACHHRA, Amit C</creatorcontrib><creatorcontrib>AMIN, Janaki</creatorcontrib><creatorcontrib>LAW, Matthew G</creatorcontrib><creatorcontrib>EMERY, Sean</creatorcontrib><creatorcontrib>GERSTOFT, Jan</creatorcontrib><creatorcontrib>CORDIN, Fred M</creatorcontrib><creatorcontrib>VJECHA, Michael J</creatorcontrib><creatorcontrib>NEATON, James D</creatorcontrib><creatorcontrib>COOPER, David A</creatorcontrib><creatorcontrib>INSIGHT ESPRIT & SILCAAT study groups</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>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ACHHRA, Amit C</au><au>AMIN, Janaki</au><au>LAW, Matthew G</au><au>EMERY, Sean</au><au>GERSTOFT, Jan</au><au>CORDIN, Fred M</au><au>VJECHA, Michael J</au><au>NEATON, James D</au><au>COOPER, David A</au><aucorp>INSIGHT ESPRIT & SILCAAT study groups</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2010-07-31</date><risdate>2010</risdate><volume>24</volume><issue>12</issue><spage>1877</spage><epage>1886</epage><pages>1877-1886</pages><issn>0269-9370</issn><eissn>1473-5571</eissn><abstract>To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints.
Observational.
Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count.
Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03).
Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>20588170</pmid><doi>10.1097/qad.0b013e32833b1b26</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0269-9370 |
| ispartof | AIDS (London), 2010-07, Vol.24 (12), p.1877-1886 |
| issn | 0269-9370 1473-5571 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Adult Antiretroviral Therapy, Highly Active Biological and medical sciences CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology Disease Progression Endpoint Determination Female HIV Infections - drug therapy HIV Infections - immunology HIV Infections - mortality HIV-1 - immunology Human immunodeficiency virus Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunologic Deficiency Syndromes - drug therapy Immunologic Deficiency Syndromes - immunology Immunologic Deficiency Syndromes - mortality Immunopathology Infectious diseases Male Medical sciences Predictive Value of Tests Proportional Hazards Models Prospective Studies Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients |
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