New signatures of poor CD4 cell recovery after suppressive antiretroviral therapy in HIV-1-infected individuals: involvement of miR-192, IL-6, sCD14 and miR-144

Francisco Hernández-Walias,Santiago Moreno,María J Ruiz-De-León,Alejandro Vallejo,Isaac Rosado-Sánchez,Esther Vázquez,Manuel Leal,Yolanda M Pacheco,Francesc Vidal,Julià Blanco

doi:10.1038/s41598-020-60073-8

Abstract

Up to 40% of newly diagnosed cases of HIV-1 infection are late diagnoses, with a profound decrease in CD4 cell counts in many cases. One-third of these individuals do not achieve optimal CD4 cell recovery (OR) after suppressive antiretroviral treatment (ART). This retrospective/longitudinal study of poor recovery (PR) included 79 HIV-1-infected individuals with CD4 count <200 cells/mm3 (25 PR and 54 OR) before ART. After suppressive ART, 21 PR and 24 OR individuals were further analysed, including paired samples. Selected miRs and plasma inflammatory markers were determined to investigate their potential predictive/diagnostic value for poor recovery. miR-192, IL-6 and sCD14 were independently associated with CD4 recovery before ART (p = 0.031, p = 0.007, and p = 0.008, respectively). The combination of these three factors returned a good discrimination (predictive value for PR) value of 0.841 (AUC, p < 0.001). After suppressive ART, miR-144 was independently associated with CD4 recovery (p = 0.017), showing a moderate discrimination value of 0.730 (AUC, p = 0.008) for PR. Our study provides new evidence on the relationship between miRs and HIV-1 infection that could help improve the management of individuals at HIV-1 diagnosis. These miRs and cytokines signature sets provide novel tools to predict CD4 cell recovery and its progression after ART.

Highlights

Diagnosed cases of HIV-1 infection include individuals with a late diagnosis who often have a low level of CD4 cell counts
This retrospective/longitudinal study of adult HIV-1-infected individuals was performed with samples at antiretroviral treatment (ART) onset and after 96 weeks of suppressive ART collected from the Spanish AIDS Research Network Cohort (CoRIS) through its HIV Biobank (Spain)[20,21], and the HIV-1-infected individuals Cohort of the University Hospital Ramon y Cajal (Madrid, Spain)
To find predictive biomarkers at ART onset to identify earlier those HIV-1-infected individuals who will have poor CD4 cell recovery after suppressive ART is crucial for the good management of HIV-1-infected individuals[4,26]

Summary

Introduction

Diagnosed cases of HIV-1 infection include individuals with a late diagnosis who often have a low level of CD4 cell counts. Disease presence and progression have been associated with an increase of both exosome release and their molecular content. These molecules could influence the homeostasis cell balance, promoting hematopoietic stem cells and, by modifying the levels of soluble cytokines, regulate the immune system[12,13,14]. Since exosomes can modulate immune responses and might affect HIV-1 pathogenesis, we conducted this longitudinal study to quantify selected miRs and soluble inflammatory markers in HIV-1-infected individuals at ART onset and after 96 weeks under suppressive ART to investigate their potential predictive and diagnostic value of poor CD4 cell recovery

Methods

Results

Conclusion