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

Mahnke, Yolanda D.a; Song, Kaimeia; Sauer, Mariana M.b; Nason, Martha C.c; Giret, Maria Teresa M.b,d; Carvalho, Karina I.b; Costa, Priscilla R.b; Roederer, Marioa; Kallás, Esper G.b

AIDS:
doi: 10.1097/QAD.0b013e32835ce2e9
Basic Science
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 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.

Author Information

aImmunoTechnology Section, VRC, NIAID, NIH, Bethesda, Maryland, USA

bDivision of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil

cBiostatistics Research Branch, NIAID, NIH, Bethesda, Maryland

dTwo Story Lab, Miller School of Medicine, University of Florida, Miami, Florida, USA.

Correspondence to Yolanda D. Mahnke, PhD, 40 Convent Drive, Rm 5608, Bethesda, MD 20892, USA. Tel: +1 301 594 8655; fax: +1 301 480 2788; e-mail: mahnkey@mail.nih.gov

Received 31 August, 2012

Revised 1 November, 2012

Accepted 21 November, 2012

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© 2013 Lippincott Williams & Wilkins, Inc.