Abstract
BackgroundApproximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition.MethodsA total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro.ResultsExpression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux.ConclusionWe established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients.
Highlights
Most people infected with the human immunodeficiency virus (HIV) who receive antiretroviral therapy (ART) respond well to treatment, and are able to maintain an undetectable viral load [1]
To determine specific miRNAs with predictive capacity for the response to ART, a total of 307 people with HIV infection on ART were enrolled, and sorted into groups corresponding to the four phases of our study
In the first phase, 444 miRNAs were tested among seven immune non-responders (INRs), seven immune responders (IRs), and five negative control individuals (NCs)
Summary
Most people infected with the human immunodeficiency virus (HIV) who receive antiretroviral therapy (ART) respond well to treatment, and are able to maintain an undetectable viral load [1]. Previous research has shown that immunological, genetic, and viral factors are related to a poor immune response to ART, such as defective bone marrow and thymus functions, chronic immune activation and inflammation, polymorphisms in the CD14 and toll-like receptor genes, and accumulation of lipid metabolites in plasma [8,9,10] Some clinical indicators, such as age [11], baseline or nadir CD4+ T cell counts [12, 13], activated programmed cell death protein 1 (PD-1)+ CD4+ T cells [14], metabolomic signatures [15], and gene polymorphisms [16], are predictors for recovery of CD4+ T cells after ART. 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART) These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition
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