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

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 08/2009; 49(6):956-64. DOI: 10.1086/605503
Source: PubMed

ABSTRACT 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.
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.
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).
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.

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Available from: Karen Suzanne Bishop, Sep 28, 2015
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    • "Firstly, due to limited PBMCs available from the patients we focused on Gag peptides and did not investigate responses to whole viral proteins. However, Gag, especially the p24 protein, is one of the most important target antigens for viral control [36], [45], [46], due to their role in the selection of escape mutations that lead to viral fitness costs [47], its sequence stability compared to other viral particles [1], [2], [7], the abundance of the protein on incoming virions [48], as well as its rapid antigen presentation following viral infection [49]. For the development of a globally effective CTL-induced vaccine, detailed mapping of Gag epitopes and their restricting HLA alleles will be essential. "
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    • "One HLA-B allele (B*42:01) that has shown some consistency in its association with better control of viremia [32], [33], [35]had a clearly unfavorable effect on acquisition (Table 1). The B*42-C*17 haplotype is carried in 18.8% of Zambians. "
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    PLoS ONE 08/2011; 6(8):e23469. DOI:10.1371/journal.pone.0023469 · 3.23 Impact Factor
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    • "HLA variants shown here have been confirmed in further analyses (generalized linear models, Table 4) or reported in earlier studies of native Africans with HIV-1C infection [28], [35], [41], [42]. "
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