Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients

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.

Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity

“…These five miRNAs were utilized to create a predictive algorithm that could successfully and precisely distinguish INRs from IRs to predict PIR following ART. Furthermore, miR-16-5p might prevent the growth of CD4 + T cells by regulating calcium flow ( 142 ). These prognostic miRNA biomarkers may enhance the early detection of PIR.…”

microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway

“… 31 In addition, miR-16-5p has been documented to predict poor immune response following antiretroviral therapy in HIV-infected patients. 32 Also, Li et al . observed that miR-16-5p was involved in the promoting effects of M1 macrophage-released exosomes on T cell-dependent immune response via PD-L1 in GC.…”

The diverse roles of miRNAs in HIV pathogenesis: Current understanding and future perspectives

“…Approximately 10-40% of HIV-infected patients fail to achieve meaningful or sustained improvement in immune function after ART. Therefore, investigation of potential roles that miRNAs may play in immune recovery during or after antiretroviral therapy (ART) in HIV-1 patients and immunological non-responders (INRs) has already been initiated ( 17 , 19 , 80 ). miRNA sponges are RNA transcripts which include long non coding RNAs (lncRNAs) and circular RNAs (circRNAs), that associate with and sequester miRNAs, thus not allowing them to interact with their target mRNAs ( 81 ).…”

“…Past evidence has demonstrated that miRNAs are involved not only in HIV pathogenesis before treatment, but also in the immune recovery process during antiretroviral therapy (ART), and may serve as biomarkers and even as predictive markers for immune responses after initiation of ART (17)(18)(19). This review aims to summarize major advancements made in the field of miRNAs and HIV.…”