To identify early determinants of HIV-1 disease progression, which could potentially enable individualized patient treatment, and provide correlates of progression applicable as reference phenotypes to evaluate breakthrough infections in vaccine development.Design:
High-throughput technologies were employed to interrogate multiple parameters on cryopreserved, retrospective peripheral blood mononuclear cell (PBMC) samples from 51 individuals from São Paulo, Brazil, obtained within 1 year of diagnosing early Clade B HIV-1 infection. Fast Progressors, Slow Progressors, and Controllers were identified based on a 2-year clinical follow-up.Methods:
Phenotypic and functional T-cell parameters were tested by flow cytometry and qPCR to identify potential early determinants of subsequent HIV-1 disease progression.Results:
Major differences were observed between Controllers and Progressors, especially in cell-associated viral load (CAVL), the differentiation pattern and CD38 expression of CD8+ T cells, and the cytokine pattern and activation phenotype of HIV-1-specific CD8+ T cells. Despite remarkably few other differences between the two Progressor groups, the CAVL had predictive power independent of plasma viral load.Conclusion:
Analysis of three parameters (% CD38+ CD8+ T cells, total CAVL, % CCR5+ CD8+ T cells) was sufficient to predict subsequent disease progression (P < 0.001). Use of such prognostic correlates may be crucial when early CD4+ T-cell counts and plasma viral load levels fail to discriminate among groups with differing subsequent clinical progression.