A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy
Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses a...
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| Veröffentlicht in: | BMC infectious diseases 2014-09, Vol.14 (1), p.521-521, Article 521 |
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| creator | Canipe, Ashley Chidumayo, Takondwa Blevins, Meridith Bestawros, Michael Bala, Jay Kelly, Paul Filteau, Suzanne Shepherd, Bryan E Heimburger, Douglas C Koethe, John R |
| description | Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation.
HIV-infected, Zambian adults with a body mass index |
| doi_str_mv | 10.1186/1471-2334-14-521 |
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HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.
Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers.
In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/1471-2334-14-521</identifier><identifier>PMID: 25266928</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Acute-Phase Proteins ; Adult ; Analysis ; Anti-HIV Agents - therapeutic use ; Bacterial Translocation ; Biomarkers ; Biomarkers - blood ; Biomedical research ; Body mass index ; C-Reactive Protein - metabolism ; Carrier Proteins - blood ; Clinical trials ; Developing countries ; Disease ; Disease susceptibility ; Drug therapy ; Female ; Gastrointestinal Tract - immunology ; Gastrointestinal Tract - microbiology ; Health aspects ; Hepatology ; HIV ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - microbiology ; Human immunodeficiency virus ; Humans ; Immunocompromised Host ; Infections ; Inflammation - blood ; Inflammation Mediators - blood ; LDCs ; Longitudinal Studies ; Male ; Malnutrition ; Malnutrition - immunology ; Malnutrition - virology ; Medical research ; Medicine ; Medicine, Experimental ; Membrane Glycoproteins - blood ; Mitogens ; Mortality ; Permeability ; Pilot Projects ; Revisions ; Risk Factors ; Studies ; Teaching hospitals ; Tumor Necrosis Factor-alpha - blood ; Urine ; Zambia</subject><ispartof>BMC infectious diseases, 2014-09, Vol.14 (1), p.521-521, Article 521</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Canipe et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Canipe et al.; licensee BioMed Central Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b722t-738b080d067c22c785d1f475d479e1905a7982d61e2ee145a2e579a7506867f13</citedby><cites>FETCH-LOGICAL-b722t-738b080d067c22c785d1f475d479e1905a7982d61e2ee145a2e579a7506867f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261887/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261887/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25266928$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Canipe, Ashley</creatorcontrib><creatorcontrib>Chidumayo, Takondwa</creatorcontrib><creatorcontrib>Blevins, Meridith</creatorcontrib><creatorcontrib>Bestawros, Michael</creatorcontrib><creatorcontrib>Bala, Jay</creatorcontrib><creatorcontrib>Kelly, Paul</creatorcontrib><creatorcontrib>Filteau, Suzanne</creatorcontrib><creatorcontrib>Shepherd, Bryan E</creatorcontrib><creatorcontrib>Heimburger, Douglas C</creatorcontrib><creatorcontrib>Koethe, John R</creatorcontrib><title>A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy</title><title>BMC infectious diseases</title><addtitle>BMC Infect Dis</addtitle><description>Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation.
HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.
Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers.
In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.</description><subject>Acute-Phase Proteins</subject><subject>Adult</subject><subject>Analysis</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Bacterial Translocation</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomedical research</subject><subject>Body mass index</subject><subject>C-Reactive Protein - metabolism</subject><subject>Carrier Proteins - blood</subject><subject>Clinical trials</subject><subject>Developing countries</subject><subject>Disease</subject><subject>Disease susceptibility</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Gastrointestinal Tract - immunology</subject><subject>Gastrointestinal Tract - microbiology</subject><subject>Health aspects</subject><subject>Hepatology</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - microbiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunocompromised Host</subject><subject>Infections</subject><subject>Inflammation - blood</subject><subject>Inflammation Mediators - blood</subject><subject>LDCs</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Malnutrition</subject><subject>Malnutrition - immunology</subject><subject>Malnutrition - virology</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine, Experimental</subject><subject>Membrane Glycoproteins - blood</subject><subject>Mitogens</subject><subject>Mortality</subject><subject>Permeability</subject><subject>Pilot Projects</subject><subject>Revisions</subject><subject>Risk Factors</subject><subject>Studies</subject><subject>Teaching hospitals</subject><subject>Tumor Necrosis Factor-alpha - 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therapeutic use</topic><topic>Bacterial Translocation</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomedical research</topic><topic>Body mass index</topic><topic>C-Reactive Protein - metabolism</topic><topic>Carrier Proteins - blood</topic><topic>Clinical trials</topic><topic>Developing countries</topic><topic>Disease</topic><topic>Disease susceptibility</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Gastrointestinal Tract - immunology</topic><topic>Gastrointestinal Tract - microbiology</topic><topic>Health aspects</topic><topic>Hepatology</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - microbiology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunocompromised Host</topic><topic>Infections</topic><topic>Inflammation - blood</topic><topic>Inflammation Mediators - blood</topic><topic>LDCs</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Malnutrition</topic><topic>Malnutrition - 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We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation.
HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.
Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers.
In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25266928</pmid><doi>10.1186/1471-2334-14-521</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | BMC infectious diseases, 2014-09, Vol.14 (1), p.521-521, Article 521 |
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| subjects | Acute-Phase Proteins Adult Analysis Anti-HIV Agents - therapeutic use Bacterial Translocation Biomarkers Biomarkers - blood Biomedical research Body mass index C-Reactive Protein - metabolism Carrier Proteins - blood Clinical trials Developing countries Disease Disease susceptibility Drug therapy Female Gastrointestinal Tract - immunology Gastrointestinal Tract - microbiology Health aspects Hepatology HIV HIV Infections - drug therapy HIV Infections - immunology HIV Infections - microbiology Human immunodeficiency virus Humans Immunocompromised Host Infections Inflammation - blood Inflammation Mediators - blood LDCs Longitudinal Studies Male Malnutrition Malnutrition - immunology Malnutrition - virology Medical research Medicine Medicine, Experimental Membrane Glycoproteins - blood Mitogens Mortality Permeability Pilot Projects Revisions Risk Factors Studies Teaching hospitals Tumor Necrosis Factor-alpha - blood Urine Zambia |
| title | A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T02%3A43%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%2012%20week%20longitudinal%20study%20of%20microbial%20translocation%20and%20systemic%20inflammation%20in%20undernourished%20HIV-infected%20Zambians%20initiating%20antiretroviral%20therapy&rft.jtitle=BMC%20infectious%20diseases&rft.au=Canipe,%20Ashley&rft.date=2014-09-29&rft.volume=14&rft.issue=1&rft.spage=521&rft.epage=521&rft.pages=521-521&rft.artnum=521&rft.issn=1471-2334&rft.eissn=1471-2334&rft_id=info:doi/10.1186/1471-2334-14-521&rft_dat=%3Cgale_pubme%3EA539575330%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1566945436&rft_id=info:pmid/25266928&rft_galeid=A539575330&rfr_iscdi=true |