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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Impact of select immunologic and virologic biomarkers on CD4 cell count decrease in patients with chronic HIV-1
Zabrina Brumme1, Bingxia Wang, Kriebashne Nair
1Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, USA.
Insights
Plasma viral load and human leukocyte antigen (HLA) type, not CD8 T cell responses, predict CD4 cell count decline in HIV-1 subtype C infection. These biomarkers better differentiate disease progression rates in chronically infected individuals.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Characterizing biomarkers influencing HIV-1 infection outcomes is crucial, especially for non-B subtypes.
- Previous studies suggested HIV-1 protein-specific CD8 T lymphocyte responses correlate with immune control.
- This study investigates these responses alongside clinical biomarkers in HIV-1 subtype C infection.
Purpose of the Study:
- To assess the relationship between HIV-1 protein-specific CD8 T cell responses, established biomarkers, and CD4 cell count decrease rates.
- To evaluate the predictive value of these markers for disease progression in HIV-1 subtype C-infected individuals.
- To determine if CD8 T cell responses combined with other biomarkers improve prediction of CD4 cell count decline.
Main Methods:
- Longitudinal cohort study of 300 therapy-naive adults with HIV-1 subtype C.
- Analysis using bivariate and multivariate mixed-effects models.
- Assessment of baseline CD4 cell count, plasma viral load, HLA class I alleles, and HIV-1 protein-specific CD8 T cell responses.
Main Results:
- Baseline CD4 count, viral load, and protective HLA alleles significantly correlated with CD4 cell count decrease.
- No correlation was found between HIV-1 protein-specific CD8 T cell responses and CD4 cell count decline.
- Multivariate models showed that viral load and HLA type could discriminate CD4 cell count decreases over a 10-fold range.
Conclusions:
- Plasma viral load and HLA class I type are key predictors of CD4 cell count decrease in chronic HIV-1 subtype C infection.
- In vitro HIV-1 protein-specific CD8 T cell responses did not differentiate CD4 cell count decrease rates.
- The combination of viral load and HLA type offers superior discrimination of disease progression compared to individual markers.
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.
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