Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa
Identifieur interne : 001D38 ( Pmc/Corpus ); précédent : 001D37; suivant : 001D39Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa
Auteurs : Stephen D. Lawn ; Francesca Little ; Linda-Gail Bekker ; Richard Kaplan ; Elizabeth Campbel ; Catherine Orrell ; Robin WoodSource :
- AIDS (London, England) [ 0269-9370 ] ; 2009.
Abstract
To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART).
Observational community-based ART cohort in South Africa.
CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates.
Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300– 399, 400–499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART.
Url:
DOI: 10.1097/QAD.0b013e328321823f
PubMed: 19114870
PubMed Central: 3776050
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PMC:3776050Le document en format XML
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<author><name sortKey="Lawn, Stephen D" sort="Lawn, Stephen D" uniqKey="Lawn S" first="Stephen D." last="Lawn">Stephen D. Lawn</name>
<affiliation><nlm:aff id="A1">The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa</nlm:aff>
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<affiliation><nlm:aff id="A2">Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK</nlm:aff>
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<author><name sortKey="Little, Francesca" sort="Little, Francesca" uniqKey="Little F" first="Francesca" last="Little">Francesca Little</name>
<affiliation><nlm:aff id="A3">Faculty of Science, Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa</nlm:aff>
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<author><name sortKey="Bekker, Linda Gail" sort="Bekker, Linda Gail" uniqKey="Bekker L" first="Linda-Gail" last="Bekker">Linda-Gail Bekker</name>
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<author><name sortKey="Kaplan, Richard" sort="Kaplan, Richard" uniqKey="Kaplan R" first="Richard" last="Kaplan">Richard Kaplan</name>
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<author><name sortKey="Campbel, Elizabeth" sort="Campbel, Elizabeth" uniqKey="Campbel E" first="Elizabeth" last="Campbel">Elizabeth Campbel</name>
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<author><name sortKey="Orrell, Catherine" sort="Orrell, Catherine" uniqKey="Orrell C" first="Catherine" last="Orrell">Catherine Orrell</name>
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<author><name sortKey="Wood, Robin" sort="Wood, Robin" uniqKey="Wood R" first="Robin" last="Wood">Robin Wood</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa</title>
<author><name sortKey="Lawn, Stephen D" sort="Lawn, Stephen D" uniqKey="Lawn S" first="Stephen D." last="Lawn">Stephen D. Lawn</name>
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<affiliation><nlm:aff id="A2">Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK</nlm:aff>
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<author><name sortKey="Little, Francesca" sort="Little, Francesca" uniqKey="Little F" first="Francesca" last="Little">Francesca Little</name>
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<author><name sortKey="Bekker, Linda Gail" sort="Bekker, Linda Gail" uniqKey="Bekker L" first="Linda-Gail" last="Bekker">Linda-Gail Bekker</name>
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<author><name sortKey="Kaplan, Richard" sort="Kaplan, Richard" uniqKey="Kaplan R" first="Richard" last="Kaplan">Richard Kaplan</name>
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<author><name sortKey="Campbel, Elizabeth" sort="Campbel, Elizabeth" uniqKey="Campbel E" first="Elizabeth" last="Campbel">Elizabeth Campbel</name>
<affiliation><nlm:aff id="A1">The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa</nlm:aff>
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<author><name sortKey="Orrell, Catherine" sort="Orrell, Catherine" uniqKey="Orrell C" first="Catherine" last="Orrell">Catherine Orrell</name>
<affiliation><nlm:aff id="A1">The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa</nlm:aff>
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<author><name sortKey="Wood, Robin" sort="Wood, Robin" uniqKey="Wood R" first="Robin" last="Wood">Robin Wood</name>
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<series><title level="j">AIDS (London, England)</title>
<idno type="ISSN">0269-9370</idno>
<idno type="eISSN">1473-5571</idno>
<imprint><date when="2009">2009</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title>
<p id="P1">To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART).</p>
</sec>
<sec id="S2"><title>Design</title>
<p id="P2">Observational community-based ART cohort in South Africa.</p>
</sec>
<sec id="S3"><title>Methods</title>
<p id="P3">CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates.</p>
</sec>
<sec id="S4"><title>Results</title>
<p id="P4">Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300– 399, 400–499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8710219</journal-id>
<journal-id journal-id-type="pubmed-jr-id">1493</journal-id>
<journal-id journal-id-type="nlm-ta">AIDS</journal-id>
<journal-id journal-id-type="iso-abbrev">AIDS</journal-id>
<journal-title-group><journal-title>AIDS (London, England)</journal-title>
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<issn pub-type="ppub">0269-9370</issn>
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<article-meta><article-id pub-id-type="pmid">19114870</article-id>
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<article-id pub-id-type="doi">10.1097/QAD.0b013e328321823f</article-id>
<article-id pub-id-type="manuscript">NIHMS514745</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Lawn</surname>
<given-names>Stephen D.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Little</surname>
<given-names>Francesca</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bekker</surname>
<given-names>Linda-Gail</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaplan</surname>
<given-names>Richard</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Campbel</surname>
<given-names>Elizabeth</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Orrell</surname>
<given-names>Catherine</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wood</surname>
<given-names>Robin</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa</aff>
<aff id="A2"><label>b</label>
Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK</aff>
<aff id="A3"><label>c</label>
Faculty of Science, Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa</aff>
<author-notes><corresp id="FN1">Correspondence to Dr Stephen D. Lawn, Faculty of Health Sciences, Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. Tel: +27 21 650 6957; fax: +27 21 650 6963; <email>stevelawn@yahoo.co.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>4</day>
<month>9</month>
<year>2013</year>
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<pub-date pub-type="ppub"><day>28</day>
<month>1</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>18</day>
<month>9</month>
<year>2013</year>
</pub-date>
<volume>23</volume>
<issue>3</issue>
<fpage>335</fpage>
<lpage>342</lpage>
<abstract><sec id="S1"><title>Objective</title>
<p id="P1">To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART).</p>
</sec>
<sec id="S2"><title>Design</title>
<p id="P2">Observational community-based ART cohort in South Africa.</p>
</sec>
<sec id="S3"><title>Methods</title>
<p id="P3">CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates.</p>
</sec>
<sec id="S4"><title>Results</title>
<p id="P4">Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300– 399, 400–499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART.</p>
</sec>
</abstract>
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