Journal Article

Impact of Select Immunologic and Virologic Biomarkers on CD4 Cell Count Decrease in Patients with Chronic HIV-1 Subtype C Infection: Results from Sinikithemba Cohort, Durban, South Africa

Zabrina Brumme, Bingxia Wang, Kriebashne Nair, Chanson Brumme, Chantal de Pierres, Shabashini Reddy, Boris Julg, Eshia Moodley, Christina Thobakgale, Zhigang Lu, Mary van der Stok, Karen Bishop, Zenele Mncube, Fundisiwe Chonco, Yuko Yuki, Nicole Frahm, Christian Brander, Mary Carrington, Kenneth Freedberg, Photini Kiepiela, Philip Goulder, Bruce Walker, Thumbi Ndung'u and Elena Losina

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 6, pages 956-964
Published in print September 2009 | ISSN: 1058-4838
Published online September 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/605503
Impact of Select Immunologic and Virologic Biomarkers on CD4 Cell Count Decrease in Patients with Chronic HIV-1 Subtype C Infection: Results from Sinikithemba Cohort, Durban, South Africa

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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/mm3and 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/mm3), plasma viral load (⩽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/mm3and plasma viral loads >100,000 copies/mL with no protective HLA alleles (−59 cells/mm3per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm3, plasma viral loads ⩽100,000 copies/mL, and a protective HLA allele (−6 cells/mm3per 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.

Journal Article.  5345 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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