| Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. | |
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MedLine Citation:
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PMID: 20629534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Microbial translocation contributes to immune activation and disease progression during chronic human immunodeficiency virus type 1 (HIV-1) infection. However, its role in the African AIDS epidemic remains controversial. Here, we investigated the relationship between markers of monocyte activation, plasma lipopolysaccharide (LPS), and HIV-1 RNA in South Africans prioritized to receive combination antiretroviral therapy (cART). METHODS: Ten HIV-1-negative African controls and 80 HIV-1-infected patients with CD4 T cell counts <200 cells/microL were sampled prior to (n=60) or during (n=20) receipt of effective cART. Viral load was measured by Nuclisens; LPS by the Limulus amoebocyte lysate assay; monocyte and T cell subsets by flow cytometry; and soluble CD14, cytokines, and chemokines by enzyme-linked immunosorbent assay and customized Bio-Plex plates. RESULTS: Three distinct sets of markers were identified. CCL2, CXCL10, and CD14(+)CD16(+) monocyte levels were positively correlated with HIV-1 viremia. This finding, together with cART-induced normalization of these markers, suggests that their upregulation was driven by HIV-1. Plasma interleukin-6 was associated with the presence of opportunistic coinfections. Soluble CD14 and tumor necrosis factor were linked to plasma LPS levels and, as observed for LPS, remained elevated in patients receiving effective cART. CONCLUSIONS: Microbial translocation is a major force driving chronic inflammation in HIV-infected Africans receiving cART. Prevention of monocyte activation may be especially effective at enhancing therapeutic outcomes. |
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Authors:
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Edana Cassol; Susan Malfeld; Phetole Mahasha; Schalk van der Merwe; Sharon Cassol; Chris Seebregts; Massimo Alfano; Guido Poli; Theresa Rossouw |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 202 ISSN: 1537-6613 ISO Abbreviation: J. Infect. Dis. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-09-02 Revised Date: 2011-02-28 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 723-33 Citation Subset: AIM; IM |
Affiliation:
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MRC Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and the Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa. edana_cassol@dfci.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AIDS-Related Opportunistic Infections
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immunology*,
microbiology Adult Anti-HIV Agents / therapeutic use* CD4 Lymphocyte Count Drug Therapy, Combination Female HIV Infections / drug therapy*, immunology, virology HIV-1 / genetics, immunology Humans Lipopolysaccharides / blood* Lymphocyte Activation Male Middle Aged Monocytes / immunology* RNA, Viral / blood Viral Load |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Lipopolysaccharides; 0/RNA, Viral |
| Comments/Corrections | |
Comment In:
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J Infect Dis. 2011 Mar;203(5):744-5; author reply 746
[PMID:
21220777
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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