Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

Gabriela Turk,Jimena Salido,María Holgado,César Trifone,Macarena Hormanstorfer,María Ruiz,Romina Coloccini,Yanina Ghiglione,Juliana Falivene,Omar Sued,Natalia Laufer,María Figueroa,Roberto Rabinovich,María Pando,Pedro Pury,María Gherardi,Luis Giavedoni,Horacio Salomón,María Caruso

doi:10.3390/v10010034

Abstract

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

Highlights

Human Immunodeficiency Virus (HIV) infection causes an irreversible deterioration of the immune system leading to the development of AIDS in the vast majority of infected persons.Following virus transmission, acute/early phase of infection is characterized by a high-level peak of viremia, rapid loss of CD4+ T-cells in both peripheral blood and mucosal lymphoid tissues, and, in some cases, clinical symptoms [1,2]
In 2008, an ongoing multicenter Argentine observational cohort of subjects diagnosed during primary HIV infection, named Grupo Argentino de Seroconversión study group, was created in Argentina
For the purposebecause of this study we early choseafter to include the following variables in in this new analysis: immune activation its level infection was associated with this new analysis: immune activation because its level early after infection was associated with disease disease progression [31], HIV‐specific T‐cell specificity because progression [31], HIV-specific T-cell specificity because we have shown that early Gag immunodominance was associated with slow rates of disease progression [28]

Summary

Introduction

Human Immunodeficiency Virus (HIV) infection causes an irreversible deterioration of the immune system leading to the development of AIDS in the vast majority of infected persons.Following virus transmission, acute/early phase of infection is characterized by a high-level peak of viremia, rapid loss of CD4+ T-cells in both peripheral blood and mucosal lymphoid tissues, and, in some cases, clinical symptoms [1,2]. Emergence of HIV-specific CD8+ T-cell response is associated with the drop of plasma viremia to a stable level; known as the viral set-point [3]. Within this general framework, it is known that the rate of disease progression after acquiring the infection is very variable among individuals, allowing the identification of different subgroups: rapid progressors, typical progressors, viremic controllers or elite controllers [4]. Finding a reliable biomarker able to predict the rate of disease progression after acute/early HIV infection remains an important challenge. The HIV treatment guidelines recommended by the United States, the World Health Organization, the International AIDS Society and the European AIDS

Objectives

Methods

Conclusion