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http://purl.uniprot.org/citations/19663693http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19663693http://www.w3.org/2000/01/rdf-schema#comment"

Background

The extent to which immunologic and clinical biomarkers influence human immunodeficiency virus type 1 (HIV-1) infection outcomes remains incompletely characterized, particularly for non-B subtypes. On the basis of data supporting in vitro HIV-1 protein-specific CD8 T lymphocyte responses as correlates of immune control in cross-sectional studies, we assessed the relationship of these responses, along with established HIV-1 biomarkers, with rates of CD4 cell count decrease in individuals infected with HIV-1 subtype C.

Methods

Bivariate and multivariate mixed-effects models were used to assess the relationship of baseline CD4 cell count, plasma viral load, human leukocyte antigen (HLA) class I alleles, and HIV-1 protein-specific CD8 T cell responses with the rate of CD4 cell count decrease in a longitudinal population-based cohort of 300 therapy-naive, chronically infected adults with baseline CD4 cell counts >200 cells/mm(3) and plasma viral loads >500 copies/mL over a median of 25 months of follow-up.

Results

In bivariate analyses, baseline CD4 cell count, plasma viral load, and possession of a protective HLA allele correlated significantly with the rate of CD4 cell count decrease. No relationship was observed between HIV-1 protein-specific CD8 T cell responses and CD4 cell count decrease. Results from multivariate models incorporating baseline CD4 cell counts (201-350 vs >350 cells/mm(3)), plasma viral load (< or =100,000 vs >100,000 copies/mL), and HLA (protective vs not protective) yielded the ability to discriminate CD4 cell count decreases over a 10-fold range. The fastest decrease was observed among individuals with CD4 cell counts >350 cells/mm(3) and plasma viral loads >100,000 copies/mL with no protective HLA alleles (-59 cells/mm(3) per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm(3), plasma viral loads < or =100,000 copies/mL, and a protective HLA allele (-6 cells/mm(3) per year).

Conclusions

The combination of plasma viral load and HLA class I type, but not in vitro HIV-1 protein-specific CD8 T cell responses, differentiates rates of CD4 cell count decrease in patients with chronic subtype-C infection better than either marker alone."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.org/dc/terms/identifier"doi:10.1086/605503"xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Carrington M."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Lu Z."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Walker B."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Reddy S."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Wang B."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Yuki Y."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Bishop K."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Julg B."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Kiepiela P."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Brander C."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Goulder P."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Moodley E."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Nair K."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Ndung'u T."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"van der Stok M."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Frahm N."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Brumme C."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Brumme Z."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Chonco F."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Losina E."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Mncube Z."xsd:string
http://purl.uniprot.org/citations/19663693http://purl.uniprot.org/core/author"Thobakgale C."xsd:string
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