title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: ImmunoTechnology Section, NIAID, NIH, Bethesda, MD, USA. mahnkey@mail.nih.gov
authors.forename: Yolanda D
authors.initials: YD
authors.lastname: Mahnke
authors.forename: Kaimei
authors.initials: K
authors.lastname: Song
authors.forename: Mariana M
authors.initials: MM
authors.lastname: Sauer
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.forename: Maria Teresa M
authors.initials: MT
authors.lastname: Giret
authors.forename: Karina I
authors.initials: KI
authors.lastname: Carvalho
authors.forename: Priscilla R
authors.initials: PR
authors.lastname: Costa
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallás
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D015415:Biomarkers; D001938:Brazil; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D019562:Viral Load / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051997:ADP-ribosyl Cyclase 1