Early immunologic and virologic predictors of clinical HIV-1 disease progression
Mahnke, Y.D.; Song, K.; Sauer, M.M.; Nason, M.C.; Giret, M.T.M.; Carvalho, K.I.; Costa, P.R.; Roederer, M.; Kallás, E.G.
Aids 27(5): 697-706
2013
ISSN/ISBN: 1473-5571 PMID: 23211771 DOI: 10.1097/qad.0b013e32835ce2e9Document Number: 576796
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. 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. Phenotypic and functional T-cell parameters were tested by flow cytometry and qPCR to identify potential early determinants of subsequent HIV-1 disease progression. 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. 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.