The extent to which immunologic and clinical biomarkers influence HIV outcomes remains incompletely characterized, particularly for non-B subtypes. Based on data supporting in vitro HIV 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 biomarkers, with rates of CD4 decline in subtype-C infection.
Bi-variate and multivariate mixed effects models were used to assess the relationship of baseline CD4, plasma viral load (pVL), HLA class I alleles, and HIV protein-specific CD8 responses with rate of CD4 decline in a longitudinal population-based cohort of 300 therapy-naïve, chronically infected adults with baseline CD4>200 cells/mm3 and pVL>500 copies/ml, over a median 25 months follow-up.
In bi-variate analyses, baseline CD4, pVL and possession of a protective HLA allele correlated significantly with rate of CD4 decline. No relationship was observed between HIV protein-specific CD8 responses and CD4 decline. Results from multivariate models, incorporating baseline CD4 (201–350 and >350), pVL (≤100,000 and >100,000), HLA (protective vs. not), yielded the ability to discriminate CD4 declines over a 10-fold range: the highest rate of decline was observed among individuals with CD4>350, pVL>100,000 with no protective HLA alleles (−59 cells/mm3/year), while the slowest decline was observed in individuals with CD4 201–350, pVL≤100,000 and a protective allele (−6 cells/mm3/year).
The combination of plasma viral load and HLA class I type, but not in vitro HIV protein-specific CD8 responses, differentiates rates of CD4 decline in chronic subtype-C infection better than either marker alone.