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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical, demographic and laboratory parameters at HAART initiation associated with decreased post-HAART survival in a U.S. military prospective HIV cohort</title><author><name sortKey="Lifson, Alan R" sort="Lifson, Alan R" uniqKey="Lifson A" first="Alan R" last="Lifson">Alan R. Lifson</name><affiliation><nlm:aff id="I1">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Krantz, Elizabeth M" sort="Krantz, Elizabeth M" uniqKey="Krantz E" first="Elizabeth M" last="Krantz">Elizabeth M. Krantz</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Grambsch, Patricia L" sort="Grambsch, Patricia L" uniqKey="Grambsch P" first="Patricia L" last="Grambsch">Patricia L. Grambsch</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Macalino, Grace E" sort="Macalino, Grace E" uniqKey="Macalino G" first="Grace E" last="Macalino">Grace E. Macalino</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Crum Cianflone, Nancy F" sort="Crum Cianflone, Nancy F" uniqKey="Crum Cianflone N" first="Nancy F" last="Crum-Cianflone">Nancy F. Crum-Cianflone</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I4">Infectious Disease, Naval Medical Center San Diego, San Diego, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ganesan, Anuradha" sort="Ganesan, Anuradha" uniqKey="Ganesan A" first="Anuradha" last="Ganesan">Anuradha Ganesan</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I5">Infectious Disease, National Naval Medical Center, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Okulicz, Jason F" sort="Okulicz, Jason F" uniqKey="Okulicz J" first="Jason F" last="Okulicz">Jason F. Okulicz</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I6">Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Eaton, Anne" sort="Eaton, Anne" uniqKey="Eaton A" first="Anne" last="Eaton">Anne Eaton</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Powers, John H" sort="Powers, John H" uniqKey="Powers J" first="John H" last="Powers">John H. Powers</name><affiliation><nlm:aff id="I7">National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E" last="Eberly">Lynn E. Eberly</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Agan, Brian K" sort="Agan, Brian K" uniqKey="Agan B" first="Brian K" last="Agan">Brian K. Agan</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22339893</idno><idno type="pmc">3320559</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320559</idno><idno type="RBID">PMC:3320559</idno><idno type="doi">10.1186/1742-6405-9-4</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002087</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002087</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Clinical, demographic and laboratory parameters at HAART initiation associated with decreased post-HAART survival in a U.S. military prospective HIV cohort</title><author><name sortKey="Lifson, Alan R" sort="Lifson, Alan R" uniqKey="Lifson A" first="Alan R" last="Lifson">Alan R. Lifson</name><affiliation><nlm:aff id="I1">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Krantz, Elizabeth M" sort="Krantz, Elizabeth M" uniqKey="Krantz E" first="Elizabeth M" last="Krantz">Elizabeth M. Krantz</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Grambsch, Patricia L" sort="Grambsch, Patricia L" uniqKey="Grambsch P" first="Patricia L" last="Grambsch">Patricia L. Grambsch</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Macalino, Grace E" sort="Macalino, Grace E" uniqKey="Macalino G" first="Grace E" last="Macalino">Grace E. Macalino</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Crum Cianflone, Nancy F" sort="Crum Cianflone, Nancy F" uniqKey="Crum Cianflone N" first="Nancy F" last="Crum-Cianflone">Nancy F. Crum-Cianflone</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I4">Infectious Disease, Naval Medical Center San Diego, San Diego, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ganesan, Anuradha" sort="Ganesan, Anuradha" uniqKey="Ganesan A" first="Anuradha" last="Ganesan">Anuradha Ganesan</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I5">Infectious Disease, National Naval Medical Center, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Okulicz, Jason F" sort="Okulicz, Jason F" uniqKey="Okulicz J" first="Jason F" last="Okulicz">Jason F. Okulicz</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I6">Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Eaton, Anne" sort="Eaton, Anne" uniqKey="Eaton A" first="Anne" last="Eaton">Anne Eaton</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Powers, John H" sort="Powers, John H" uniqKey="Powers J" first="John H" last="Powers">John H. Powers</name><affiliation><nlm:aff id="I7">National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E" last="Eberly">Lynn E. Eberly</name><affiliation><nlm:aff id="I2">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Agan, Brian K" sort="Agan, Brian K" uniqKey="Agan B" first="Brian K" last="Agan">Brian K. Agan</name><affiliation><nlm:aff id="I3">Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</nlm:aff></affiliation></author></analytic><series><title level="j">AIDS Research and Therapy</title><idno type="eISSN">1742-6405</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality.</p></sec><sec><title>Methods</title><p>We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel.</p></sec><sec><title>Results</title><p>Cumulative mortality was 5%, 10% and 18% at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years [PY]) in those with ≤ 50 CD4+ cells/mm<sup>3 </sup>before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with ≥ 500 CD4+ cells/mm<sup>3</sup>). In multivariate analysis, factors significantly (p < 0.05) associated with post-HAART mortality included: increasing age among those ≥ 40 years (Hazard ratio [HR] = 1.32 per 5 year increase), clinical AIDS events before HAART (HR = 1.93), ≤ 50 CD4+ cells/mm<sup>3 </sup>(vs. CD4+ ≥ 500, HR = 2.97), greater HIV RNA level (HR = 1.36 per one log<sub>10 </sub>increase), hepatitis C antibody or chronic hepatitis B (HR = 1.96), and HIV diagnosis before 1996 (HR = 2.44). Baseline CD4+ = 51-200 cells (HR = 1.74, p = 0.06), and hemoglobin < 12 gm/dL for women or < 13.5 for men (HR = 1.36, p = 0.07) were borderline significant.</p></sec><sec><title>Conclusions</title><p>Although treatment has improved HIV survival, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory correlates of poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mocroft, A" uniqKey="Mocroft A">A Mocroft</name></author><author><name sortKey="Ledergerber, B" uniqKey="Ledergerber B">B Ledergerber</name></author><author><name sortKey="Katlama, C" uniqKey="Katlama C">C Katlama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walensky, Rp" uniqKey="Walensky R">RP Walensky</name></author><author><name sortKey="Paltiel, Ad" uniqKey="Paltiel A">AD Paltiel</name></author><author><name sortKey="Losina, E" uniqKey="Losina E">E Losina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lohse, N" uniqKey="Lohse N">N Lohse</name></author><author><name sortKey="Hansen, Ab" uniqKey="Hansen A">AB Hansen</name></author><author><name sortKey="Pedersen, G" uniqKey="Pedersen G">G Pedersen</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Harris, Rj" uniqKey="Harris R">RJ Harris</name></author><author><name sortKey="Sterne, Ja" uniqKey="Sterne J">JA Sterne</name></author><author><name sortKey="Abgrall, S" uniqKey="Abgrall S">S Abgrall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moh, R" uniqKey="Moh R">R Moh</name></author><author><name sortKey="Danel, C" uniqKey="Danel C">C Danel</name></author><author><name sortKey="Messou, E" uniqKey="Messou E">E Messou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaen, A" uniqKey="Jaen A">A Jaen</name></author><author><name sortKey="Esteve, A" uniqKey="Esteve A">A Esteve</name></author><author><name sortKey="Miro, Jm" uniqKey="Miro J">JM Miro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kitahata, Mm" uniqKey="Kitahata M">MM Kitahata</name></author><author><name sortKey="Gange, Sj" uniqKey="Gange S">SJ Gange</name></author><author><name sortKey="Abraham, Ag" uniqKey="Abraham A">AG Abraham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="May, M" uniqKey="May M">M May</name></author><author><name sortKey="Boulle, A" uniqKey="Boulle A">A Boulle</name></author><author><name sortKey="Phiri, S" uniqKey="Phiri S">S Phiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lima, Vd" uniqKey="Lima V">VD Lima</name></author><author><name sortKey="Hogg, Rs" uniqKey="Hogg R">RS Hogg</name></author><author><name sortKey="Harrigan, Pr" uniqKey="Harrigan P">PR Harrigan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marconi, Vc" uniqKey="Marconi V">VC Marconi</name></author><author><name sortKey="Grandits, Ga" uniqKey="Grandits G">GA Grandits</name></author><author><name sortKey="Weintrob, Ac" uniqKey="Weintrob A">AC Weintrob</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Lifson, Ar" uniqKey="Lifson A">AR Lifson</name></author><author><name sortKey="Krantz, Em" uniqKey="Krantz E">EM Krantz</name></author><author><name sortKey="Eberly, Le" uniqKey="Eberly L">LE Eberly</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Mugavero, Mj" uniqKey="Mugavero M">MJ Mugavero</name></author><author><name sortKey="Napravnik, S" uniqKey="Napravnik S">S Napravnik</name></author><author><name sortKey="Cole, Sr" uniqKey="Cole S">SR Cole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, H" uniqKey="Zhao H">H Zhao</name></author><author><name sortKey="Goetz, Mb" uniqKey="Goetz M">MB Goetz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Althoff, Kn" uniqKey="Althoff K">KN Althoff</name></author><author><name sortKey="Gebo, Ka" uniqKey="Gebo K">KA Gebo</name></author><author><name sortKey="Gange, Sj" uniqKey="Gange S">SJ Gange</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weber, R" uniqKey="Weber R">R Weber</name></author><author><name sortKey="Sabin, Ca" uniqKey="Sabin C">CA Sabin</name></author><author><name sortKey="Friis Moller, N" uniqKey="Friis Moller N">N Friis-Moller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smit, C" uniqKey="Smit C">C Smit</name></author><author><name sortKey="Van Den Berg, C" uniqKey="Van Den Berg C">C van den Berg</name></author><author><name sortKey="Geskus, R" uniqKey="Geskus R">R Geskus</name></author><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B Berkhout</name></author><author><name sortKey="Coutinho, R" uniqKey="Coutinho R">R Coutinho</name></author><author><name sortKey="Prins, M" uniqKey="Prins M">M Prins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thio, Cl" uniqKey="Thio C">CL Thio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, Dl" uniqKey="Thomas D">DL Thomas</name></author><author><name sortKey="Astemborski, J" uniqKey="Astemborski J">J Astemborski</name></author><author><name sortKey="Rai, Rm" uniqKey="Rai R">RM Rai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sulkowski, Ms" uniqKey="Sulkowski M">MS Sulkowski</name></author><author><name sortKey="Cheever, Lw" uniqKey="Cheever L">LW Cheever</name></author><author><name sortKey="Spach, Dh" uniqKey="Spach D">DH Spach</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">AIDS Res Ther</journal-id><journal-id journal-id-type="iso-abbrev">AIDS Res Ther</journal-id><journal-title-group><journal-title>AIDS Research and Therapy</journal-title></journal-title-group><issn pub-type="epub">1742-6405</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22339893</article-id><article-id pub-id-type="pmc">3320559</article-id><article-id pub-id-type="publisher-id">1742-6405-9-4</article-id><article-id pub-id-type="doi">10.1186/1742-6405-9-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Short Report</subject></subj-group></article-categories><title-group><article-title>Clinical, demographic and laboratory parameters at HAART initiation associated with decreased post-HAART survival in a U.S. military prospective HIV cohort</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes" id="A1"><name><surname>Lifson</surname><given-names>Alan R</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I3">3</xref><email>lifso001@umn.edu</email></contrib><contrib contrib-type="author" id="A2"><name><surname>Krantz</surname><given-names>Elizabeth M</given-names></name><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I3">3</xref><email>ekrantz@ccbr.umn.edu</email></contrib><contrib contrib-type="author" id="A3"><name><surname>Grambsch</surname><given-names>Patricia L</given-names></name><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I3">3</xref><email>gramb001@umn.edu</email></contrib><contrib contrib-type="author" id="A4"><name><surname>Macalino</surname><given-names>Grace E</given-names></name><xref ref-type="aff" rid="I3">3</xref><email>gmacalino@idcrp.org</email></contrib><contrib contrib-type="author" id="A5"><name><surname>Crum-Cianflone</surname><given-names>Nancy F</given-names></name><xref ref-type="aff" rid="I3">3</xref><xref ref-type="aff" rid="I4">4</xref><email>nancy.crum@med.navy.mil</email></contrib><contrib contrib-type="author" id="A6"><name><surname>Ganesan</surname><given-names>Anuradha</given-names></name><xref ref-type="aff" rid="I3">3</xref><xref ref-type="aff" rid="I5">5</xref><email>anuradha.ganesan@med.navy.mil</email></contrib><contrib contrib-type="author" id="A7"><name><surname>Okulicz</surname><given-names>Jason F</given-names></name><xref ref-type="aff" rid="I3">3</xref><xref ref-type="aff" rid="I6">6</xref><email>jason.okulicz@amedd.army.mil</email></contrib><contrib contrib-type="author" id="A8"><name><surname>Eaton</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="I2">2</xref><email>eatona@mskcc.org</email></contrib><contrib contrib-type="author" id="A9"><name><surname>Powers</surname><given-names>John H</given-names></name><xref ref-type="aff" rid="I7">7</xref><email>powersjo@niaid.nih.gov</email></contrib><contrib contrib-type="author" id="A10"><name><surname>Eberly</surname><given-names>Lynn E</given-names></name><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I3">3</xref><email>lynn@biostat.umn.edu</email></contrib><contrib contrib-type="author" corresp="yes" id="A11"><name><surname>Agan</surname><given-names>Brian K</given-names></name><xref ref-type="aff" rid="I3">3</xref><email>bagan@idcrp.org</email></contrib><on-behalf-of>the Infectious Disease Clinical Research Program HIV/STI Working Group bagan@idcrp.org</on-behalf-of></contrib-group><aff id="I1"><label>1</label>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</aff><aff id="I2"><label>2</label>Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</aff><aff id="I3"><label>3</label>Infectious Disease Clinical Research Program, Uniformed Services University of Health Sciences, Bethesda, MD, USA</aff><aff id="I4"><label>4</label>Infectious Disease, Naval Medical Center San Diego, San Diego, CA, USA</aff><aff id="I5"><label>5</label>Infectious Disease, National Naval Medical Center, Bethesda, MD, USA</aff><aff id="I6"><label>6</label>Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, USA</aff><aff id="I7"><label>7</label>National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA</aff><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>10</day><month>2</month><year>2012</year></pub-date><volume>9</volume><fpage>4</fpage><lpage>4</lpage><history><date date-type="received"><day>19</day><month>9</month><year>2011</year></date><date date-type="accepted"><day>10</day><month>2</month><year>2012</year></date></history><permissions><copyright-statement>Copyright ©2012 Lifson et al; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>Lifson et al; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri xlink:href="http://www.aidsrestherapy.com/content/9/1/4"></self-uri><abstract><sec><title>Background</title><p>Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality.</p></sec><sec><title>Methods</title><p>We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel.</p></sec><sec><title>Results</title><p>Cumulative mortality was 5%, 10% and 18% at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years [PY]) in those with ≤ 50 CD4+ cells/mm<sup>3 </sup>before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with ≥ 500 CD4+ cells/mm<sup>3</sup>). In multivariate analysis, factors significantly (p < 0.05) associated with post-HAART mortality included: increasing age among those ≥ 40 years (Hazard ratio [HR] = 1.32 per 5 year increase), clinical AIDS events before HAART (HR = 1.93), ≤ 50 CD4+ cells/mm<sup>3 </sup>(vs. CD4+ ≥ 500, HR = 2.97), greater HIV RNA level (HR = 1.36 per one log<sub>10 </sub>increase), hepatitis C antibody or chronic hepatitis B (HR = 1.96), and HIV diagnosis before 1996 (HR = 2.44). Baseline CD4+ = 51-200 cells (HR = 1.74, p = 0.06), and hemoglobin < 12 gm/dL for women or < 13.5 for men (HR = 1.36, p = 0.07) were borderline significant.</p></sec><sec><title>Conclusions</title><p>Although treatment has improved HIV survival, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory correlates of poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.</p></sec></abstract><kwd-group><kwd>Highly active antiretroviral therapy</kwd><kwd>mortality</kwd><kwd>CD4+ lymphocyte count</kwd></kwd-group></article-meta></front><body><sec><title>Introduction</title><p>Although highly active antiretroviral therapy (HAART) has significantly reduced mortality in HIV-infected patients [<xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref>], some patients receiving therapy are still dying. Guidelines for patients on stable HAART recommend laboratory monitoring and follow-up every 3-6 months [<xref ref-type="bibr" rid="B4">4</xref>]. However, more frequent and intensive monitoring and care may be indicated for those at greatest risk of post-HAART adverse clinical outcomes. Although CD4+ count is an important determinant of subsequent risk of death, other clinical and laboratory parameters at HAART start, as well as factors such as older age, may also affect post-HAART survival [<xref ref-type="bibr" rid="B5">5</xref>-<xref ref-type="bibr" rid="B10">10</xref>].</p><p>The U.S. Military HIV Natural History Study (NHS) is a prospective observational cohort of consenting HIV-infected military personnel [<xref ref-type="bibr" rid="B11">11</xref>]. Although HIV-positive status is an exclusion criterion for enlistment, active duty personnel undergo repeat HIV screening every 1-5 years, allowing for early diagnosis of infection; those found HIV-positive after enlistment receive free HIV specialty care, including HAART, at referral military medical centers. With NHS participants now followed for up to 14 years after HAART initiation, we examined clinical, laboratory and demographic factors at HAART initiation that were associated with subsequent mortality</p></sec><sec sec-type="methods"><title>Methods</title><p>Study cohort: We included active duty members and retirees with: (1) documented HIV serostatus; (2) CD4+ count within six months before HAART; (3) HAART initiation after July 1995, and after or within one month before NHS enrollment. The governing central institutional review board approved this substudy; NHS participants provide written informed consent.</p><p>Variables for analysis: We evaluated death reports from participating centers through November 2010. A National Death Index (NDI) match was also conducted to capture deaths through 12/31/06 among participants lost to follow-up. Patients not known to have died who remained under follow-up had follow-up period censored at date of last clinic visit; those lost to follow-up had follow-up censored at 12/31/06 (corresponding to NDI search).</p><p>"Baseline" for this analysis was date of HAART initiation. Baseline CD4+ count and HIV RNA level were values closest to HAART initiation in the six months before HAART. Clinical AIDS events were those in the Centers for Disease Control definition (CD4+ criteria excluded) [<xref ref-type="bibr" rid="B12">12</xref>]. Anemia was defined as hemoglobin < 12 gm/dL for women and < 13.5 gm/dL for men within three years before HAART. Body mass index (BMI) calculations used height and weight within one year before or up to 30 days after HAART initiation.</p><p>For 80% of participants with documented last negative and first positive HIV test dates, estimated HIV SC date was calculated as the midpoint. For 20%, date of first positive but not last negative test was available; SC dates were imputed based upon median times between last negative and first positive date for other cohort members with comparable first HIV positive dates [<xref ref-type="bibr" rid="B13">13</xref>]. Chronic hepatitis B virus (HBV) infection was defined as ≥ 2 positive HBV surface antigen tests ≥ 6 months apart, and hepatitis C virus (HCV) infection as a positive HCV antibody test, both determined prior to or within 30 days of HAART initiation. We defined HAART based on regimens with ≥ 2 ART classes or certain combinations of ≥ 3 nucleoside/nucleotide reverse transcriptase inhibitors (NRTI); other (non-HAART) ART was essentially mono or dual therapy.</p><p>Statistical methods: Mortality rates following HAART initiation were calculated per 100 person-years (PY) with exact Poisson 95% confidence intervals (CI). We used Kaplan-Meier summaries for cumulative mortality rates post-HAART, and Cox proportional hazards models to estimate associations between baseline covariates and mortality. Based upon visual evaluation of age at HAART start and survival, linear splines were used to model effects of age separately for those < 40 and ≥ 40 years of age.</p><p>Variables significant (p < 0.05) in univariate analyses were included in the multivariate model. The proportional hazards assumption was assessed by graphical inspection of the log-negative-log of the survival distribution plotted by log of survival time for covariate categories.</p></sec><sec><title>Results</title><p>Characteristics at HAART initiation: Table <xref ref-type="table" rid="T1">1</xref> summarizes characteristics of 1,600 persons in this analysis. Median time from estimated HIV SC to HAART initiation was 4.8 years; median baseline values were: CD4+ = 326 cells/mm<sup>3</sup>, HIV RNA = 4.5 log<sub>10 </sub>copies/ml, BMI = 25.5 kg/m<sup>2</sup>. Six percent were chronically infected with HBV and 5% HCV antibody positive; 0.5% had both. Initial HAART regimens were NRTI + protease inhibitor for 59%, NRTI + non-nucleoside reverse transcriptase inhibitor for 34%, and another regimen for 8%.</p><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Post-HAART Mortality Rate by Demographic, Clinical and Laboratory Parameters Prior to HAART Initiation, U.S. Military HIV Natural History Study</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th align="left">Number and % of Participants</th><th align="left">Number of Deaths</th><th align="left">Deaths/100 PY (95% CI)</th></tr></thead><tbody><tr><td align="left">Gender</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Male</td><td align="left">1532 (96%)</td><td align="left">182</td><td align="left">1.53 (1.32, 1.77)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Female</td><td align="left">68 (4%)</td><td align="left">8</td><td align="left">1.37 (0.59, 2.70)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Age at HAART Initiation (years)</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> < 29</td><td align="left">395 (25%)</td><td align="left">27</td><td align="left">1.11 (0.73, 1.62)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 29-33</td><td align="left">371 (23%)</td><td align="left">49</td><td align="left">1.53 (1.13, 2.02)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 34-39</td><td align="left">454 (28%)</td><td align="left">50</td><td align="left">1.28 (0.95, 1.69)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> ≥ 40</td><td align="left">380 (24%)</td><td align="left">64</td><td align="left">2.17 (1.67, 2.77)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Race</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Caucasian</td><td align="left">712 (45%)</td><td align="left">81</td><td align="left">1.40 (1.12, 1.75)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> African American</td><td align="left">686 (43%)</td><td align="left">93</td><td align="left">1.70 (1.38, 2.09)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Other</td><td align="left">202 (13%)</td><td align="left">16</td><td align="left">1.27 (0.72, 2.06)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">BMI at HAART initiation (kg/m<sup>2</sup>)</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> < 25</td><td align="left">642 (40%)</td><td align="left">87</td><td align="left">1.70 (1.36, 2.10)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 25 to < 30</td><td align="left">584 (37%)</td><td align="left">54</td><td align="left">1.23 (0.92, 1.61)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> ≥ 30</td><td align="left">210 (13%)</td><td align="left">16</td><td align="left">1.07 (0.61, 1.74)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Unknown</td><td align="left">164 (10%)</td><td align="left">33</td><td align="left">2.23 (1.54, 3.13)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Clinical AIDS event prior to HAART</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> No</td><td align="left">1468 (92%)</td><td align="left">138</td><td align="left">1.20 (1.01, 1.42)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Yes</td><td align="left">132 (8%)</td><td align="left">52</td><td align="left">5.23 (3.90, 6.85)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">CD4+ count at HAART initiation (cells/mm<sup>3</sup>)</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> ≤ 50</td><td align="left">112 (7%)</td><td align="left">53</td><td align="left">6.23 (4.67, 8.15)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 51-200</td><td align="left">259 (16%)</td><td align="left">48</td><td align="left">2.19 (1.61, 2.90)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 201-349</td><td align="left">517 (32%)</td><td align="left">42</td><td align="left">1.15 (0.83, 1.56)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 350-499</td><td align="left">433 (27%)</td><td align="left">30</td><td align="left">0.89 (0.60, 1.27)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> ≥ 500</td><td align="left">279 (17%)</td><td align="left">17</td><td align="left">0.70 (0.41, 1.12)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">HIV RNA at HAART initiation (copies/ml)</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> < 1000</td><td align="left">139 (9%)</td><td align="left">10</td><td align="left">0.80 (0.38, 1.47)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 1000-9999</td><td align="left">316 (20%)</td><td align="left">23</td><td align="left">0.86 (0.55, 1.29)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 10,000-99,999</td><td align="left">752 (47%)</td><td align="left">79</td><td align="left">1.38 (1.09, 1.72)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> ≥ 100,000</td><td align="left">393 (25%)</td><td align="left">78</td><td align="left">2.75 (2.18, 3.44)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Anemia within 3 years</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> No</td><td align="left">941 (59%)</td><td align="left">60</td><td align="left">0.87 (0.66, 1.12)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Yes</td><td align="left">635 (40%)</td><td align="left">127</td><td align="left">2.34 (1.95, 2.79)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Unknown</td><td align="left">24 (2%)</td><td align="left">3</td><td align="left">1.96 (0.40, 5.73)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Chronic HBV or HCV antibody positive</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> No</td><td align="left">1385 (87%)</td><td align="left">138</td><td align="left">1.29 (1.09, 1.53)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Yes</td><td align="left">166 (10%)</td><td align="left">48</td><td align="left">3.44 (2.54, 4.56)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Unknown</td><td align="left">49 (3%)</td><td align="left">4</td><td align="left">0.95 (0.26, 2.42)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Year of HIV diagnosis</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Before 1996</td><td align="left">848 (53%)</td><td align="left">167</td><td align="left">2.00 (1.71, 2.33)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 1996 or after</td><td align="left">752 (47%)</td><td align="left">23</td><td align="left">0.56 (0.35, 0.83)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Year of HAART initiation</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Before 2000</td><td align="left">967 (60%)</td><td align="left">171</td><td align="left">1.74 (1.49, 2.02)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 2000-2010</td><td align="left">633 (40%)</td><td align="left">19</td><td align="left">0.72 (0.43, 1.13)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Time from SC to HAART initiation (years)</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> < 2</td><td align="left">473 (30%)</td><td align="left">16</td><td align="left">0.55 (0.31, 0.89)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 2-5</td><td align="left">353 (22%)</td><td align="left">31</td><td align="left">1.20 (0.82, 1.71)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> 5 to < 9</td><td align="left">383 (24%)</td><td align="left">64</td><td align="left">1.83 (1.41, 2.33)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> ≥ 9</td><td align="left">391 (24%)</td><td align="left">79</td><td align="left">2.26 (1.79, 2.82)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Other (non-HAART) ART</td><td></td><td></td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> No</td><td align="left">835 (52%)</td><td align="left">30</td><td align="left">0.61 (0.41, 0.87)</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left"> Yes</td><td align="left">765 (48%)</td><td align="left">160</td><td align="left">2.12 (1.80, 2.48)</td></tr></tbody></table></table-wrap><p>Mortality rates: Median follow-up post-HAART was 8.7 years, or 12,486 PY. During follow-up, there were 190 deaths, or 1.52 deaths per 100 PY (95% CI 1.31, 1.75). Cumulative mortality was 5% (95% CI 4%-6%) at 4 years, 10% (95% CI 9%-12%) at 8 years, and 18% (95% CI 15%-20%) at 12 years. Mortality was highest in those with ≤ 50 cells/mm<sup>3 </sup>prior to HAART, and became progressively lower as CD4+ count increased (Table <xref ref-type="table" rid="T1">1</xref>, Figure <xref ref-type="fig" rid="F1">1</xref>). Mortality rates progressively increased with greater baseline HIV RNA levels and longer time from HIV SC to HAART initiation. Mortality rates by other baseline factors are in Table <xref ref-type="table" rid="T1">1</xref>.</p><fig id="F1" position="float"><label>Figure 1</label><caption><p><bold>Cumulative Proportion Surviving by Baseline CD4+ Count Prior to HAART Initiation, U.S. Military HIV Natural History Study</bold>.</p></caption><graphic xlink:href="1742-6405-9-4-1"></graphic></fig><p>Predictors of mortality: In univariate analysis, participants with CD4+ ≤ 50 cells/mm<sup>3 </sup>and 51-200 cells/mm<sup>3 </sup>at HAART initiation had significantly (p < 0.05) increased mortality compared to ≥ 500 CD4+ cells (Table <xref ref-type="table" rid="T2">2</xref>). Mortality significantly increased with older age among those ≥ 40 years, but not among those < 40 years. Other factors significantly associated with increased mortality included clinical AIDS events before HAART, greater HIV RNA levels, anemia, HCV/chronic HBV, HIV diagnosis before 1996, HAART initiation before 2000, longer time from SC to HAART initiation, and non-HAART ART use (Table <xref ref-type="table" rid="T2">2</xref>).</p><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Univariate and Multivariate Model Estimates for Post-HAART Mortality by Baseline Parameters Prior to HAART Initiation, U.S. Military HIV Natural History Study</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Baseline Covariate (at HAART initiation)</th><th align="left">Univariate Hazard Ratio (95% CI)</th><th align="left">Multivariate Hazard Ratio (95% CI)</th></tr></thead><tbody><tr><td align="left">Gender: Female vs. Male</td><td align="left">0.89 (0.44, 1.80)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Age:</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> per 5 years older if age < 40 years</td><td align="left">1.11 (0.95, 1.30)</td><td align="left">0.91 (0.76, 1.08)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> per 5 years older if age ≥ 40 years</td><td align="left">1.27 (1.12, 1.44)**</td><td align="left">1.32 (1.16, 1.51)**</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Race</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Caucasian</td><td align="left">1.00 (Reference)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> African American</td><td align="left">1.22 (0.91, 1.65)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Other</td><td align="left">0.92 (0.54, 1.58)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">BMI</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> < 25</td><td align="left">1.00 (Reference)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> 25 to < 30</td><td align="left">0.73 (0.52, 1.03)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> ≥ 30</td><td align="left">0.64 (0.38, 1.10)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Unknown</td><td align="left">1.29 (0.87, 1.93)</td><td align="left">--- †</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Clinical AIDS event prior to HAART</td><td align="left">4.26 (3.09, 5.87)**</td><td align="left">1.93 (1.33, 2.81)**</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">CD4+ count at (cells/mm<sup>3</sup>)</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> ≤ 50</td><td align="left">8.91 (5.15, 15.40)**</td><td align="left">2.97 (1.56, 5.65)**</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> 51-200</td><td align="left">3.07 (1.76, 5.35) **</td><td align="left">1.74 (0.97, 3.12)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> 201-349</td><td align="left">1.69 (0.96, 2.98)</td><td align="left">1.39 (0.79, 2.46)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> 350-499</td><td align="left">1.29 (0.71, 2.35)</td><td align="left">1.21 (0.66, 2.19)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> ≥ 500</td><td align="left">1.00 (Reference)</td><td align="left">1.00 (Reference)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">HIV RNA (copies/ml) per one log<sub>10 </sub>increase</td><td align="left">1.72 (1.44, 2.04)**</td><td align="left">1.36 (1.12, 1.64)*</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Anemia within 3 years</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> No</td><td align="left">1.00 (Reference)</td><td align="left">1.00 (Reference)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Yes</td><td align="left">2.61 (1.92, 3.55)**</td><td align="left">1.36 (0.97, 1.92)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Unknown</td><td align="left">2.29 (0.72, 7.30)</td><td align="left">1.96 (0.40, 5.73)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Chronic HBV or HCV antibody positive</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> No</td><td align="left">1.00 (Reference)</td><td align="left">1.00 (Reference)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Yes</td><td align="left">2.61 (1.88, 3.63)**</td><td align="left">1.96 (1.39, 2.76)**</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Unknown</td><td align="left">0.73 (0.27, 1.99)</td><td align="left">0.98 (0.36, 2.67)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Year of HIV diagnosis</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Before 1996</td><td align="left">3.35 (2.16, 5.21)**</td><td align="left">2.44 (1.51, 3.93)**</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> 1996 or after</td><td align="left">1.00 (Reference)</td><td align="left">1.00 (Reference)</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Year of HAART initiation</td><td></td><td></td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> Before 2000</td><td align="left">2.13 (1.31, 3.46)*</td><td align="left">--- ††</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left"> 2000-2010</td><td align="left">1.00 (Reference)</td><td align="left">--- ††</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Time from SC to HAART (years) per 1 year increase</td><td align="left">1.10 (1.06, 1.14)**</td><td align="left">--- ††</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Other (non-HAART) ART</td><td align="left">3.28 (2.21, 4.87)**</td><td align="left">--- ††</td></tr></tbody></table><table-wrap-foot><p>* p = 0.002 ** p < 0.001</p><p>† Multivariate model included only variables significant in univariate analysis</p><p>†† Not included in multivariate model because of strong collinearity with Year of HIV diagnosis</p></table-wrap-foot></table-wrap><p>Exploratory analysis found strong colinearity between years from SC to HAART initiation, HIV diagnosis era, era of HAART initiation, and other ART use. For multivariate models, we chose HIV diagnosis before or after 1996, when HAART generally became available. Multivariate factors significantly associated with mortality included: increasing age among those ≥ 40 years, clinical AIDS event before HAART, CD4+ ≤ 50 cells/mm<sup>3</sup>, greater HIV RNA level, HCV/chronic HBV, and HIV diagnosis before 1996 (Table <xref ref-type="table" rid="T2">2</xref>). Anemia within three years prior to HAART (p = 0.07), and CD4+ = 51-200 cells/mm<sup>3 </sup>(p = 0.06) were of borderline significance.</p><p>In additional exploratory analyses, we added gender and race (as potential confounders), or initial HAART regimen class to our multivariate model; none of these was significantly associated with mortality.</p></sec><sec><title>Discussion</title><p>Among HIV-infected military personnel, factors at HAART initiation associated with poorer survival included greater age in those ≥ 40 years, lower CD4+ count, greater HIV RNA level, prior clinical AIDS event, HIV diagnosis before 1996, and either HCV or chronic HBV; in multivariate analysis, anemia was borderline significant.</p><p>Consistent with other studies [<xref ref-type="bibr" rid="B14">14</xref>-<xref ref-type="bibr" rid="B16">16</xref>], mortality rates progressively decreased from lowest to highest baseline CD4+ strata, from 6.23 deaths in ≤ 50 CD4+ cell strata to 0.70 deaths/100 PY in the ≥ 500 CD4+ strata. While we did not find statistically significant mortality differences between higher CD4+ levels [<xref ref-type="bibr" rid="B8">8</xref>], this may reflect limited power from smaller numbers of deaths in higher CD4+ categories.</p><p>Higher HIV RNA level prior to HAART predicted increased mortality even after adjusting for CD4+ count and prior clinical AIDS. One potential explanation is if those with higher HIV RNA levels had longer time to viral suppression after HAART initiation, and/or did not develop viral suppression before death. Ongoing HIV replication may place patients at greater risk of opportunistic disease or death [<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>].</p><p>Among those ≥ 40 years, older age at HAART start was associated with poorer prognosis. Other analyses of HIV patients in the HAART era also report decreased survival with older age [<xref ref-type="bibr" rid="B8">8</xref>-<xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B18">18</xref>]. Given increasing recognition of HIV in those ≥ 50 years [<xref ref-type="bibr" rid="B19">19</xref>,<xref ref-type="bibr" rid="B20">20</xref>], older patients initiating HIV care and treatment require more intensive monitoring and follow-up.</p><p>In this analysis, we combined chronic HBV and HCV antibody positivity, since HIV patients co-infected with either virus have increased mortality from liver-related deaths [<xref ref-type="bibr" rid="B21">21</xref>-<xref ref-type="bibr" rid="B23">23</xref>]. Although we did not have access to HCV RNA, the great majority of HCV antibody-positive HIV patients likely had chronic HCV infection [<xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B24">24</xref>]. Providers should know current guidelines for co-infected patient including, when appropriate, therapy against HBV or HCV [<xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B25">25</xref>].</p><p>This cohort of HIV-infected military personnel has several strengths. Medical and other support provided to participants (including free HIV treatment) minimize socioeconomic disadvantage and lack of access to care that might otherwise influence outcome. Viral suppression rates in this cohort were reported to approach those in clinical trials [<xref ref-type="bibr" rid="B11">11</xref>]. The cohort is ethnically diverse. We can estimate time from HIV SC to HAART start. Follow-up extended for some patients to 14 years, longer than many other studies.</p><p>Our analysis has several limitations. We focused on baseline factors at HAART initiation, and not time-updated post-HAART changes. Our endpoint was overall mortality, rather than specific causes of death. Group differences in mortality may be due to additional unmeasured confounding factors. Populations with different demographic or risk characteristics may have different predictors of survival.</p><p>In summary, although HAART has improved survival for persons with HIV, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory indicators associated with poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.</p></sec><sec><title>Competing interests</title><p>The authors declare that they have no competing interests.</p></sec><sec><title>Authors' contributions</title><p>AL was lead author on planning and coordinating the analysis, and drafting interim and final versions of the manuscript. EK, PG, AE, and LE provided statistical support and assistance with various aspects of the analysis. GM, NC, AG, JO, BA had multiple responsibilities related to this cohort, including data collection and oversight at study sites at which participants were followed. Co-authors all provided feedback and offered valuable comments and suggestions on versions of this manuscript. All co-authors have seen and approved the final version of this manuscript.</p></sec></body><back><sec><title>Acknowledgements and funding</title><p>Additional members of the Infectious Disease Clinical Research Program HIV/STI Working Group include Susan Banks, Mary Bavaro, Helen Chun, Cathy Decker, Connor Eggleston, Susan Fraser, Joshua Hartzell, Gunther Hsue, Arthur Johnson, Mark Kortepeter, Tahaniyat Lalani, Michael Landrum, Michelle Linfesty, Scott Merritt, Robert O'Connell, Sheila Peel, Michael Polis, Roseanne Ressnerk, Edmund Tramont, Tyler Warkentien, Paige Waterman, Amy Weintrob, Timothy Whitman, Glenn Wortmann, and Michael Zapor. The content and views expressed in this publication is the sole responsibility of the authors and does not necessarily reflect the views or policies of the NIH or the Department of Health and Human Services, the DoD or the Departments of the Army, Navy, Air Force, Department of Defense, nor the U.S. Government. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Support for this work (IDCRP-000-14) was provided by the Infectious Disease Clinical Research Program, a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072.</p></sec><ref-list><ref id="B1"><mixed-citation publication-type="journal"><name><surname>Mocroft</surname><given-names>A</given-names></name><name><surname>Ledergerber</surname><given-names>B</given-names></name><name><surname>Katlama</surname><given-names>C</given-names></name><etal></etal><article-title>Decline in the AIDS and death rates in the EuroSIDA study: an observational study</article-title><source>Lancet</source><year>2003</year><volume>362</volume><fpage>22</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(03)13802-0</pub-id><pub-id pub-id-type="pmid">12853195</pub-id></mixed-citation></ref><ref id="B2"><mixed-citation publication-type="journal"><name><surname>Walensky</surname><given-names>RP</given-names></name><name><surname>Paltiel</surname><given-names>AD</given-names></name><name><surname>Losina</surname><given-names>E</given-names></name><etal></etal><article-title>The survival benefits of AIDS treatment in the United States</article-title><source>J Infect Dis</source><year>2006</year><volume>194</volume><fpage>11</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1086/505147</pub-id><pub-id pub-id-type="pmid">16741877</pub-id></mixed-citation></ref><ref id="B3"><mixed-citation publication-type="journal"><name><surname>Lohse</surname><given-names>N</given-names></name><name><surname>Hansen</surname><given-names>AB</given-names></name><name><surname>Pedersen</surname><given-names>G</given-names></name><etal></etal><article-title>Survival of persons with and without HIV infection in Denmark, 1995-2005</article-title><source>Ann Intern Med</source><year>2007</year><volume>146</volume><fpage>87</fpage><lpage>95</lpage><pub-id pub-id-type="pmid">17227932</pub-id></mixed-citation></ref><ref id="B4"><mixed-citation publication-type="book"><collab>Panel on Antiretroviral Guidelines for Adults and Adolescents</collab><source>Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents</source><year>2011</year><publisher-name>Dept. Health and Human Services</publisher-name><fpage>1</fpage><lpage>167</lpage><ext-link ext-link-type="uri" xlink:href="http://www.aidsinfo.nih.gov/Contentfiles/AdultandAdolescentGL.pdf">http://www.aidsinfo.nih.gov/Contentfiles/AdultandAdolescentGL.pdf</ext-link></mixed-citation></ref><ref id="B5"><mixed-citation publication-type="journal"><name><surname>Harris</surname><given-names>RJ</given-names></name><name><surname>Sterne</surname><given-names>JA</given-names></name><name><surname>Abgrall</surname><given-names>S</given-names></name><etal></etal><article-title>Prognostic importance of anaemia in HIV type-1-infected patients starting antiretroviral therapy: collaborative analysis of prospective cohort studies</article-title><source>Antivir Ther</source><year>2008</year><volume>13</volume><fpage>959</fpage><lpage>67</lpage><pub-id pub-id-type="pmid">19195321</pub-id></mixed-citation></ref><ref id="B6"><mixed-citation publication-type="journal"><name><surname>Moh</surname><given-names>R</given-names></name><name><surname>Danel</surname><given-names>C</given-names></name><name><surname>Messou</surname><given-names>E</given-names></name><etal></etal><article-title>Incidence and determinants of mortality and morbidity following early antiretroviral therapy initiation in HIV-infected adults in West Africa</article-title><source>AIDS</source><year>2007</year><volume>21</volume><fpage>2483</fpage><lpage>91</lpage><pub-id pub-id-type="doi">10.1097/QAD.0b013e3282f09876</pub-id><pub-id pub-id-type="pmid">18025885</pub-id></mixed-citation></ref><ref id="B7"><mixed-citation publication-type="journal"><name><surname>Jaen</surname><given-names>A</given-names></name><name><surname>Esteve</surname><given-names>A</given-names></name><name><surname>Miro</surname><given-names>JM</given-names></name><etal></etal><article-title>Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain)</article-title><source>J Acquir Immune Defic Syndr</source><year>2008</year><volume>47</volume><fpage>212</fpage><lpage>20</lpage><pub-id pub-id-type="doi">10.1097/QAI.0b013e31815ee282</pub-id><pub-id pub-id-type="pmid">18297762</pub-id></mixed-citation></ref><ref id="B8"><mixed-citation publication-type="journal"><name><surname>Kitahata</surname><given-names>MM</given-names></name><name><surname>Gange</surname><given-names>SJ</given-names></name><name><surname>Abraham</surname><given-names>AG</given-names></name><etal></etal><article-title>Effect of early versus deferred antiretroviral therapy for HIV on survival</article-title><source>N Engl J Med</source><year>2009</year><volume>360</volume><fpage>1815</fpage><lpage>26</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa0807252</pub-id><pub-id pub-id-type="pmid">19339714</pub-id></mixed-citation></ref><ref id="B9"><mixed-citation publication-type="journal"><name><surname>May</surname><given-names>M</given-names></name><name><surname>Boulle</surname><given-names>A</given-names></name><name><surname>Phiri</surname><given-names>S</given-names></name><etal></etal><article-title>Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes</article-title><source>Lancet</source><year>2010</year><volume>376</volume><fpage>449</fpage><lpage>57</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(10)60666-6</pub-id><pub-id pub-id-type="pmid">20638120</pub-id></mixed-citation></ref><ref id="B10"><mixed-citation publication-type="journal"><name><surname>Lima</surname><given-names>VD</given-names></name><name><surname>Hogg</surname><given-names>RS</given-names></name><name><surname>Harrigan</surname><given-names>PR</given-names></name><etal></etal><article-title>Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy</article-title><source>AIDS</source><year>2007</year><volume>21</volume><fpage>685</fpage><lpage>92</lpage><pub-id pub-id-type="doi">10.1097/QAD.0b013e32802ef30c</pub-id><pub-id pub-id-type="pmid">17413689</pub-id></mixed-citation></ref><ref id="B11"><mixed-citation publication-type="journal"><name><surname>Marconi</surname><given-names>VC</given-names></name><name><surname>Grandits</surname><given-names>GA</given-names></name><name><surname>Weintrob</surname><given-names>AC</given-names></name><etal></etal><article-title>Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study</article-title><source>AIDS Res Ther</source><year>2010</year><volume>7</volume><fpage>14</fpage><pub-id pub-id-type="pmid">20507622</pub-id></mixed-citation></ref><ref id="B12"><mixed-citation publication-type="journal"><collab>Centers for Disease Control</collab><article-title>1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults</article-title><source>Morbid Mortal Wkly Rep</source><year>1992</year><volume>41</volume><issue>RR-17</issue><fpage>1</fpage><lpage>19</lpage></mixed-citation></ref><ref id="B13"><mixed-citation publication-type="journal"><name><surname>Lifson</surname><given-names>AR</given-names></name><name><surname>Krantz</surname><given-names>EM</given-names></name><name><surname>Eberly</surname><given-names>LE</given-names></name><etal></etal><article-title>Long-term CD4+ lymphocyte response following HAART initiation in a U.S. Military prospective cohort</article-title><source>AIDS Res Ther</source><year>2011</year><volume>8</volume><fpage>2</fpage><pub-id pub-id-type="pmid">21244701</pub-id></mixed-citation></ref><ref id="B14"><mixed-citation publication-type="journal"><collab>When to Start Consortium</collab><article-title>Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies</article-title><source>Lancet</source><year>2009</year><volume>373</volume><fpage>1352</fpage><lpage>63</lpage><pub-id pub-id-type="pmid">19361855</pub-id></mixed-citation></ref><ref id="B15"><mixed-citation publication-type="journal"><collab>The Antiretroviral Therapy Cohort Collaboration (ART-CC)</collab><article-title>Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements</article-title><source>AIDS</source><year>2009</year><volume>23</volume><fpage>2199</fpage><lpage>208</lpage><pub-id pub-id-type="pmid">19779320</pub-id></mixed-citation></ref><ref id="B16"><mixed-citation publication-type="journal"><collab>The HIV-CAUSAL Collaboration</collab><article-title>The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals</article-title><source>AIDS</source><year>2010</year><volume>24</volume><fpage>123</fpage><lpage>37</lpage><pub-id pub-id-type="pmid">19770621</pub-id></mixed-citation></ref><ref id="B17"><mixed-citation publication-type="journal"><collab>The Strategies for Management of Antiretroviral Therapy (SMART) Study Group</collab><article-title>Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ cell counts and HIV RNA levels during follow-up</article-title><source>J Infect Dis</source><year>2008</year><volume>197</volume><fpage>1145</fpage><lpage>55</lpage><pub-id pub-id-type="pmid">18476293</pub-id></mixed-citation></ref><ref id="B18"><mixed-citation publication-type="journal"><name><surname>Mugavero</surname><given-names>MJ</given-names></name><name><surname>Napravnik</surname><given-names>S</given-names></name><name><surname>Cole</surname><given-names>SR</given-names></name><etal></etal><article-title>Viremia copy-years predicts mortality among treatment-naive HIV-infected patients initiating antiretroviral therapy</article-title><source>Clin Infect Dis</source><year>2011</year><volume>53</volume><fpage>927</fpage><lpage>35</lpage><pub-id pub-id-type="doi">10.1093/cid/cir526</pub-id><pub-id pub-id-type="pmid">21890751</pub-id></mixed-citation></ref><ref id="B19"><mixed-citation publication-type="journal"><name><surname>Zhao</surname><given-names>H</given-names></name><name><surname>Goetz</surname><given-names>MB</given-names></name><article-title>Complications of HIV infection in an ageing population: challenges in managing older patients on long-term combination antiretroviral therapy</article-title><source>J Antimicrob Chemother</source><year>2011</year><volume>66</volume><fpage>1210</fpage><lpage>14</lpage><pub-id pub-id-type="doi">10.1093/jac/dkr058</pub-id><pub-id pub-id-type="pmid">21421583</pub-id></mixed-citation></ref><ref id="B20"><mixed-citation publication-type="journal"><name><surname>Althoff</surname><given-names>KN</given-names></name><name><surname>Gebo</surname><given-names>KA</given-names></name><name><surname>Gange</surname><given-names>SJ</given-names></name><etal></etal><article-title>CD4 count at presentation for HIV care in the United States and Canada: Are those over 50 years more likely to have a delayed presentation?</article-title><source>AIDS Res Ther</source><year>2010</year><volume>7</volume><fpage>45</fpage><pub-id pub-id-type="pmid">21159161</pub-id></mixed-citation></ref><ref id="B21"><mixed-citation publication-type="journal"><name><surname>Weber</surname><given-names>R</given-names></name><name><surname>Sabin</surname><given-names>CA</given-names></name><name><surname>Friis-Moller</surname><given-names>N</given-names></name><etal></etal><article-title>Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study</article-title><source>Arch Intern Med</source><year>2006</year><volume>166</volume><fpage>1632</fpage><lpage>41</lpage><pub-id pub-id-type="pmid">16908797</pub-id></mixed-citation></ref><ref id="B22"><mixed-citation publication-type="journal"><name><surname>Smit</surname><given-names>C</given-names></name><name><surname>van den Berg</surname><given-names>C</given-names></name><name><surname>Geskus</surname><given-names>R</given-names></name><name><surname>Berkhout</surname><given-names>B</given-names></name><name><surname>Coutinho</surname><given-names>R</given-names></name><name><surname>Prins</surname><given-names>M</given-names></name><article-title>Risk of hepatitis-related mortality increased among hepatitis C virus/HIV-coinfected drug users compared with drug users infected only with hepatitis C virus: a 20-year prospective study</article-title><source>J Acquir Immune Defic Syndr</source><year>2008</year><volume>47</volume><fpage>221</fpage><lpage>5</lpage><pub-id pub-id-type="doi">10.1097/QAI.0b013e31815d2f59</pub-id><pub-id pub-id-type="pmid">18223361</pub-id></mixed-citation></ref><ref id="B23"><mixed-citation publication-type="journal"><name><surname>Thio</surname><given-names>CL</given-names></name><article-title>Hepatitis B and human immunodeficiency virus coinfection</article-title><source>Hepatology</source><year>2009</year><volume>49</volume><issue>5 Suppl</issue><fpage>S138</fpage><lpage>45</lpage><pub-id pub-id-type="pmid">19399813</pub-id></mixed-citation></ref><ref id="B24"><mixed-citation publication-type="journal"><name><surname>Thomas</surname><given-names>DL</given-names></name><name><surname>Astemborski</surname><given-names>J</given-names></name><name><surname>Rai</surname><given-names>RM</given-names></name><etal></etal><article-title>The natural history of hepatitis C virus infection: host, viral, and environmental factors</article-title><source>JAMA</source><year>2000</year><volume>284</volume><fpage>450</fpage><lpage>6</lpage><pub-id pub-id-type="doi">10.1001/jama.284.4.450</pub-id><pub-id pub-id-type="pmid">10904508</pub-id></mixed-citation></ref><ref id="B25"><mixed-citation publication-type="book"><name><surname>Sulkowski</surname><given-names>MS</given-names></name><name><surname>Cheever</surname><given-names>LW</given-names></name><name><surname>Spach</surname><given-names>DH</given-names></name><source>A guide for evaluation and treatment of hepatitis C in adults coinfected with HIV</source><year>2011</year><publisher-name>U.S. Dept. Health and Human Services, Health Resources and Services Administration</publisher-name><ext-link ext-link-type="uri" xlink:href="http://hab.hrsa.gov/deliverhivaidscare/files/hepccoinfectguide2011.pdf">http://hab.hrsa.gov/deliverhivaidscare/files/hepccoinfectguide2011.pdf</ext-link></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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