Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy
Identifieur interne : 000502 ( Pmc/Checkpoint ); précédent : 000501; suivant : 000503Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy
Auteurs : Susannah L. Woodd ; Paul Kelly [Royaume-Uni] ; John R. Koethe [États-Unis] ; George Praygod [Tanzanie] ; Andrea M. Rehman ; Molly Chisenga [Zambie] ; Joshua Siame [Zambie] ; Douglas C. Heimburger [États-Unis] ; Henrik Friis [Danemark] ; Suzanne FilteauSource :
- BMC Infectious Diseases [ 1471-2334 ] ; 2016.
Abstract
A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation.
We analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (
The mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63).
Among malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population.
Pan African Clinical Trials Registry,
The online version of this article (doi:10.1186/s12879-016-1894-3) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12879-016-1894-3
PubMed: 27733134
PubMed Central: 5062813
Affiliations:
- Danemark, Royaume-Uni, Tanzanie, Zambie, États-Unis
- Angleterre, Grand Londres, Hovedstaden
- Copenhague, Londres
- Université de Londres
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PMC:5062813Le document en format XML
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation.</p>
</sec>
<sec><title>Methods</title>
<p>We analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (<italic>n =</italic>
1815; body mass index [BMI] <18.5 kg/m<sup>2</sup>
) were recruited at referral to ART and randomised to receive different nutritional supplements. Demographics, measures of body composition, blood electrolytes and clinical conditions were investigated as potential risk factors using Poisson regression models.</p>
</sec>
<sec><title>Results</title>
<p>The mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63).</p>
</sec>
<sec><title>Conclusion</title>
<p>Among malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population.</p>
</sec>
<sec><title>Trial registration</title>
<p>Pan African Clinical Trials Registry, <ext-link ext-link-type="uri" xlink:href="http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13">PACTR201106000300631</ext-link>
; registered on 1st June 2011.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12879-016-1894-3) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Infect. Dis</journal-id>
<journal-title-group><journal-title>BMC Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="epub">1471-2334</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27733134</article-id>
<article-id pub-id-type="pmc">5062813</article-id>
<article-id pub-id-type="publisher-id">1894</article-id>
<article-id pub-id-type="doi">10.1186/s12879-016-1894-3</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Woodd</surname>
<given-names>Susannah L</given-names>
</name>
<address><email>susannah.woodd@lshtm.ac.uk</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kelly</surname>
<given-names>Paul</given-names>
</name>
<address><email>m.p.kelly@qmul.ac.uk</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Koethe</surname>
<given-names>John R.</given-names>
</name>
<address><email>john.r.koethe@Vanderbilt.Edu</email>
</address>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Praygod</surname>
<given-names>George</given-names>
</name>
<address><email>gpraygod@gmail.com</email>
</address>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Rehman</surname>
<given-names>Andrea M.</given-names>
</name>
<address><email>andrea.rehman@lshtm.ac.uk</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chisenga</surname>
<given-names>Molly</given-names>
</name>
<address><email>mchisenga04@yahoo.co.uk</email>
</address>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siame</surname>
<given-names>Joshua</given-names>
</name>
<address><email>josiame@yahoo.com</email>
</address>
<xref ref-type="aff" rid="Aff6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Heimburger</surname>
<given-names>Douglas C.</given-names>
</name>
<address><email>douglas.heimburger@Vanderbilt.Edu</email>
</address>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Friis</surname>
<given-names>Henrik</given-names>
</name>
<address><email>hfr@nexs.ku.dk</email>
</address>
<xref ref-type="aff" rid="Aff7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Filteau</surname>
<given-names>Suzanne</given-names>
</name>
<address><email>suzanne.filteau@lshtm.ac.uk</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<aff id="Aff1"><label>1</label>
Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK</aff>
<aff id="Aff2"><label>2</label>
Barts & the London School of Medicine and Queen Mary University of London, London, UK</aff>
<aff id="Aff3"><label>3</label>
Vanderbilt University, Nashville, USA</aff>
<aff id="Aff4"><label>4</label>
National Institute for Medical Research, Mwanza, Tanzania</aff>
<aff id="Aff5"><label>5</label>
University Teaching Hospital, Lusaka, Zambia</aff>
<aff id="Aff6"><label>6</label>
University Teaching Hospital, Lusaka, Zambia</aff>
<aff id="Aff7"><label>7</label>
University of Copenhagen, Copenhagen, Denmark</aff>
</contrib-group>
<pub-date pub-type="epub"><day>12</day>
<month>10</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>12</day>
<month>10</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><year>2016</year>
</pub-date>
<volume>16</volume>
<elocation-id>562</elocation-id>
<history><date date-type="received"><day>29</day>
<month>1</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>1</day>
<month>10</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s). 2016</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p>A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation.</p>
</sec>
<sec><title>Methods</title>
<p>We analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (<italic>n =</italic>
1815; body mass index [BMI] <18.5 kg/m<sup>2</sup>
) were recruited at referral to ART and randomised to receive different nutritional supplements. Demographics, measures of body composition, blood electrolytes and clinical conditions were investigated as potential risk factors using Poisson regression models.</p>
</sec>
<sec><title>Results</title>
<p>The mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63).</p>
</sec>
<sec><title>Conclusion</title>
<p>Among malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population.</p>
</sec>
<sec><title>Trial registration</title>
<p>Pan African Clinical Trials Registry, <ext-link ext-link-type="uri" xlink:href="http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13">PACTR201106000300631</ext-link>
; registered on 1st June 2011.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12879-016-1894-3) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>Mortality risk factors</kwd>
<kwd>Malnutrition</kwd>
<kwd>ART</kwd>
<kwd>Africa</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100001713</institution-id>
<institution>European and Developing Countries Clinical Trials Partnership</institution>
</institution-wrap>
</funding-source>
<award-id>IP.2009.33011.004</award-id>
<principal-award-recipient><name><surname>Filteau</surname>
<given-names>Suzanne</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2016</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Danemark</li>
<li>Royaume-Uni</li>
<li>Tanzanie</li>
<li>Zambie</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Grand Londres</li>
<li>Hovedstaden</li>
</region>
<settlement><li>Copenhague</li>
<li>Londres</li>
</settlement>
<orgName><li>Université de Londres</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Filteau, Suzanne" sort="Filteau, Suzanne" uniqKey="Filteau S" first="Suzanne" last="Filteau">Suzanne Filteau</name>
<name sortKey="Rehman, Andrea M" sort="Rehman, Andrea M" uniqKey="Rehman A" first="Andrea M." last="Rehman">Andrea M. Rehman</name>
<name sortKey="Woodd, Susannah L" sort="Woodd, Susannah L" uniqKey="Woodd S" first="Susannah L" last="Woodd">Susannah L. Woodd</name>
</noCountry>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Kelly, Paul" sort="Kelly, Paul" uniqKey="Kelly P" first="Paul" last="Kelly">Paul Kelly</name>
</region>
</country>
<country name="États-Unis"><noRegion><name sortKey="Koethe, John R" sort="Koethe, John R" uniqKey="Koethe J" first="John R." last="Koethe">John R. Koethe</name>
</noRegion>
<name sortKey="Heimburger, Douglas C" sort="Heimburger, Douglas C" uniqKey="Heimburger D" first="Douglas C." last="Heimburger">Douglas C. Heimburger</name>
</country>
<country name="Tanzanie"><noRegion><name sortKey="Praygod, George" sort="Praygod, George" uniqKey="Praygod G" first="George" last="Praygod">George Praygod</name>
</noRegion>
</country>
<country name="Zambie"><noRegion><name sortKey="Chisenga, Molly" sort="Chisenga, Molly" uniqKey="Chisenga M" first="Molly" last="Chisenga">Molly Chisenga</name>
</noRegion>
<name sortKey="Siame, Joshua" sort="Siame, Joshua" uniqKey="Siame J" first="Joshua" last="Siame">Joshua Siame</name>
</country>
<country name="Danemark"><region name="Hovedstaden"><name sortKey="Friis, Henrik" sort="Friis, Henrik" uniqKey="Friis H" first="Henrik" last="Friis">Henrik Friis</name>
</region>
</country>
</tree>
</affiliations>
</record>
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