Abstract:
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 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.
