Early immunologic and virologic predictors of clinical HIV-1 disease progression

Abstract

Objective: 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 Sao 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. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:697-706