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

Author(s)

Mahnke, Yolanda D. ^[1] ; Song, Kaimei ^[1] ; Sauer, Mariana M. ^[2] ; Nason, Martha C. ^[3] ; Giret, Maria Teresa M. ^{[2, 4]} ; Carvalho, Karina I. ^[2] ; Costa, Priscilla R. ^[2] ; Roederer, Mario ^[1] ; Kallas, Esper G. ^[2]

Affiliation

^[1] NIAID, ImmunoTechnol Sect, VRC, NIH, Bethesda, MD 20892 - USA

^[2] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo - Brazil

^[3] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 - USA

^[4] Univ Florida, Miller Sch Med, Story Lab 2, Miami, FL - USA

• Document type: Journal article
• Source: AIDS; v. 27, n. 5, p. 697-706, MAR 13 2013.
• Web of Science Citations: 7

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 (AU)

• FAPESP's process: 04/15856-9 - Prospective analysis of the virological and immunological characteristics in individuals with recent HIV-1 infection in the cities of São Paulo and Santos
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 06/50096-0 - Characterization of Human Immunodeficiency Virus type 1 (HIV-1) in a cohort of recently infected persons from the State of São Paulo by full genome sequencing
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral