Persistently elevated serum interleukin-6 predicts mortality among adults receiving combination antiretroviral therapy in Botswana: results from a clinical trial.
Identifieur interne : 001412 ( PubMed/Curation ); précédent : 001411; suivant : 001413Persistently elevated serum interleukin-6 predicts mortality among adults receiving combination antiretroviral therapy in Botswana: results from a clinical trial.
Auteurs : Bethan Mcdonald [États-Unis] ; Sikhulile Moyo ; Lesego Gabaitiri ; Simani Gaseitsiwe ; Hermann Bussmann ; John R. Koethe ; Rosemary Musonda ; Joseph Makhema ; Vladimir Novitsky ; Richard G. Marlink ; C William Wester ; Max EssexSource :
- AIDS research and human retroviruses [ 1931-8405 ] ; 2013.
Descripteurs français
- KwdFr :
- Adulte, Agents antiVIH (administration et posologie), Association de médicaments, Botswana (épidémiologie), Femelle, Humains, Infections à VIH (mortalité), Infections à VIH (sang), Infections à VIH (traitement médicamenteux), Interleukine-6 (sang), Marqueurs biologiques (sang), Mâle, Médiateurs de l'inflammation (sang), VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Études cas-témoins, Études de cohortes, Études rétrospectives.
- MESH :
- administration et posologie : Agents antiVIH.
- mortalité : Infections à VIH.
- sang : Infections à VIH, Interleukine-6, Marqueurs biologiques, Médiateurs de l'inflammation.
- traitement médicamenteux : Infections à VIH.
- épidémiologie : Botswana.
- Adulte, Association de médicaments, Femelle, Humains, Mâle, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Études cas-témoins, Études de cohortes, Études rétrospectives.
- Wicri :
- geographic : Botswana.
English descriptors
- KwdEn :
- Adult, Anti-HIV Agents (administration & dosage), Biomarkers (blood), Botswana (epidemiology), Case-Control Studies, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections (blood), HIV Infections (drug therapy), HIV Infections (mortality), HIV-1, Humans, Inflammation Mediators (blood), Interleukin-6 (blood), Male, Retrospective Studies.
- MESH :
- chemical , administration & dosage : Anti-HIV Agents.
- chemical , blood : Biomarkers, Inflammation Mediators, Interleukin-6.
- geographic , epidemiology : Botswana.
- blood : HIV Infections.
- drug therapy : HIV Infections.
- mortality : HIV Infections.
- Adult, Case-Control Studies, Cohort Studies, Drug Therapy, Combination, Female, HIV-1, Humans, Male, Retrospective Studies.
Abstract
Elevated serum levels of inflammatory biomarkers have been associated with increased mortality and morbidity among HIV-infected individuals receiving combination antiretroviral therapy (cART) in European and U.S. cohorts. Few similar data are available from sub-Saharan Africa, where most cART-treated adults reside and the prevalence of advanced immunosuppression and opportunistic infections (OIs) at cART initiation is higher. This was a retrospective nested case-control analysis of clinical trial data from the completed Adult Antiretroviral Treatment and Drug Resistance ("Tshepo") study, 2002-2007, Gaborone, Botswana. We measured pretreatment serum levels of interleukin-6 (IL-6), high sensitivity C-reactive protein, and D-dimer in stored plasma samples from 32 deceased participants (cases) and 64 survivors (controls), matched for age, sex, baseline CD4(+) cell count, and plasma HIV-1 RNA. Multivariate conditional logistic regression analyses were used to compare inflammatory biomarker levels, adjusting for pretreatment body mass index (BMI) and the presence of OIs. A total of 37 (5.7%) of 650 patients died on study, for a crude mortality rate of 20.6/1,000 person-years. Of 37 (86%) study participants who died on study 32 were included in this analysis. Causes of death (n=32) included non-AIDS-defining events (31.3%), HIV-related OIs (28.1%), cART/toxicity-related (21.9%), other infectious etiologies (15.6%), and unknown (3.1%). Median time to death was 31 weeks [interquartile range (IQR) 14-64]. Median baseline levels of all three biomarkers were higher in cases compared to matched controls. After adjusting for BMI and the presence of OIs, only baseline and most recent (near time of event) levels of IL-6 remained as significant predictors of all-cause mortality [adjusted OR (aOR)=1.25, 95% CI (1.05-1.48); p=0.012; and aOR=1.48 (1.05-2.09); p=0.027, respectively]. Serum IL-6 levels are important predictors of all-cause mortality in this adult urban sub-Saharan African cART-treated population. Future translational studies are warranted to better elucidate pathophysiology and inform the design of novel interventions to ameliorate the risk of death among these "at-risk" individuals.
DOI: 10.1089/aid.2012.0309
PubMed: 23590237
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Few similar data are available from sub-Saharan Africa, where most cART-treated adults reside and the prevalence of advanced immunosuppression and opportunistic infections (OIs) at cART initiation is higher. This was a retrospective nested case-control analysis of clinical trial data from the completed Adult Antiretroviral Treatment and Drug Resistance ("Tshepo") study, 2002-2007, Gaborone, Botswana. We measured pretreatment serum levels of interleukin-6 (IL-6), high sensitivity C-reactive protein, and D-dimer in stored plasma samples from 32 deceased participants (cases) and 64 survivors (controls), matched for age, sex, baseline CD4(+) cell count, and plasma HIV-1 RNA. Multivariate conditional logistic regression analyses were used to compare inflammatory biomarker levels, adjusting for pretreatment body mass index (BMI) and the presence of OIs. A total of 37 (5.7%) of 650 patients died on study, for a crude mortality rate of 20.6/1,000 person-years. Of 37 (86%) study participants who died on study 32 were included in this analysis. Causes of death (n=32) included non-AIDS-defining events (31.3%), HIV-related OIs (28.1%), cART/toxicity-related (21.9%), other infectious etiologies (15.6%), and unknown (3.1%). Median time to death was 31 weeks [interquartile range (IQR) 14-64]. Median baseline levels of all three biomarkers were higher in cases compared to matched controls. After adjusting for BMI and the presence of OIs, only baseline and most recent (near time of event) levels of IL-6 remained as significant predictors of all-cause mortality [adjusted OR (aOR)=1.25, 95% CI (1.05-1.48); p=0.012; and aOR=1.48 (1.05-2.09); p=0.027, respectively]. Serum IL-6 levels are important predictors of all-cause mortality in this adult urban sub-Saharan African cART-treated population. Future translational studies are warranted to better elucidate pathophysiology and inform the design of novel interventions to ameliorate the risk of death among these "at-risk" individuals.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23590237</PMID><DateCreated><Year>2013</Year><Month>06</Month><Day>14</Day></DateCreated><DateCompleted><Year>2013</Year><Month>09</Month><Day>10</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1931-8405</ISSN><JournalIssue CitedMedium="Internet"><Volume>29</Volume><Issue>7</Issue><PubDate><Year>2013</Year><Month>Jul</Month></PubDate></JournalIssue><Title>AIDS research and human retroviruses</Title><ISOAbbreviation>AIDS Res. Hum. Retroviruses</ISOAbbreviation></Journal><ArticleTitle>Persistently elevated serum interleukin-6 predicts mortality among adults receiving combination antiretroviral therapy in Botswana: results from a clinical trial.</ArticleTitle><Pagination><MedlinePgn>993-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1089/AID.2012.0309</ELocationID><Abstract><AbstractText>Elevated serum levels of inflammatory biomarkers have been associated with increased mortality and morbidity among HIV-infected individuals receiving combination antiretroviral therapy (cART) in European and U.S. cohorts. Few similar data are available from sub-Saharan Africa, where most cART-treated adults reside and the prevalence of advanced immunosuppression and opportunistic infections (OIs) at cART initiation is higher. This was a retrospective nested case-control analysis of clinical trial data from the completed Adult Antiretroviral Treatment and Drug Resistance ("Tshepo") study, 2002-2007, Gaborone, Botswana. We measured pretreatment serum levels of interleukin-6 (IL-6), high sensitivity C-reactive protein, and D-dimer in stored plasma samples from 32 deceased participants (cases) and 64 survivors (controls), matched for age, sex, baseline CD4(+) cell count, and plasma HIV-1 RNA. Multivariate conditional logistic regression analyses were used to compare inflammatory biomarker levels, adjusting for pretreatment body mass index (BMI) and the presence of OIs. A total of 37 (5.7%) of 650 patients died on study, for a crude mortality rate of 20.6/1,000 person-years. Of 37 (86%) study participants who died on study 32 were included in this analysis. Causes of death (n=32) included non-AIDS-defining events (31.3%), HIV-related OIs (28.1%), cART/toxicity-related (21.9%), other infectious etiologies (15.6%), and unknown (3.1%). Median time to death was 31 weeks [interquartile range (IQR) 14-64]. Median baseline levels of all three biomarkers were higher in cases compared to matched controls. After adjusting for BMI and the presence of OIs, only baseline and most recent (near time of event) levels of IL-6 remained as significant predictors of all-cause mortality [adjusted OR (aOR)=1.25, 95% CI (1.05-1.48); p=0.012; and aOR=1.48 (1.05-2.09); p=0.027, respectively]. Serum IL-6 levels are important predictors of all-cause mortality in this adult urban sub-Saharan African cART-treated population. Future translational studies are warranted to better elucidate pathophysiology and inform the design of novel interventions to ameliorate the risk of death among these "at-risk" individuals.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>McDonald</LastName><ForeName>Bethan</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Harvard School of Public Health AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moyo</LastName><ForeName>Sikhulile</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Gabaitiri</LastName><ForeName>Lesego</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Gaseitsiwe</LastName><ForeName>Simani</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Bussmann</LastName><ForeName>Hermann</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Koethe</LastName><ForeName>John R</ForeName><Initials>JR</Initials></Author><Author ValidYN="Y"><LastName>Musonda</LastName><ForeName>Rosemary</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Makhema</LastName><ForeName>Joseph</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Novitsky</LastName><ForeName>Vladimir</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Marlink</LastName><ForeName>Richard G</ForeName><Initials>RG</Initials></Author><Author ValidYN="Y"><LastName>Wester</LastName><ForeName>C William</ForeName><Initials>CW</Initials></Author><Author ValidYN="Y"><LastName>Essex</LastName><ForeName>Max</ForeName><Initials>M</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K23 AI073141</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K23 AI100700</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30AI 060354</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>D43 TW000004</GrantID><Acronym>TW</Acronym><Agency>FIC NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 AI060354</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>05</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>AIDS Res Hum Retroviruses</MedlineTA><NlmUniqueID>8709376</NlmUniqueID><ISSNLinking>0889-2229</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019380">Anti-HIV Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C508600">IL6 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018836">Inflammation Mediators</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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RefType="Cites"><RefSource>J Infect Dis. 2010 Jun 15;201(12):1788-95</RefSource><PMID Version="1">20446848</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Eur J Cardiovasc Prev Rehabil. 2010 Oct;17(5):491-501</RefSource><PMID Version="1">20543702</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Acquir Immune Defic Syndr. 2010 Nov;55(3):316-22</RefSource><PMID Version="1">20581689</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Int AIDS Soc. 2011;14:19</RefSource><PMID Version="1">21477359</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019380" MajorTopicYN="N">Anti-HIV Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015415" 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