IrsiCaixa

15/09/2009

Clin Infect Dis 49:956-964.

AbstractBackground. 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 therapynaive, chronically infected adults with baseline CD4 cell counts 1200 cells/mm3 and plasma viral loads 1500 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 1350 cells/mm3), plasma viral load (
100,000 vs 1100,000 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 1350 cells/mm3 and plasma viral loads 1100,000 copies/mL with no protective HLA alleles (59 cells/mm3 per 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/mm3 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.