Development and validation of plasma miRNA biomarker signature panel for the detection of early HIV-1 infection.

Authors:
Santanu Biswas
Santanu Biswas
Bose Institute
India
Mohan Haleyurgirisetty
Mohan Haleyurgirisetty
Laboratory of Molecular Virology
Indira Hewlett
Indira Hewlett
New York University School of Medicine
United States
Krishnakumar Devadas
Krishnakumar Devadas
Laboratory of Molecular Virology

EBioMedicine 2019 May 18;43:307-316. Epub 2019 Apr 18.

Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA. Electronic address:

Background: Accurate laboratory diagnosis of HIV is essential to reduce the risk of HIV-positive individuals transmitting HIV-1 infection. The goal of this study was to identify and assess a panel of host derived plasma miRNAs that could to serve as a prognostic and predictive biomarker to detect early/acute HIV-1 infection.

Methods: A total of 372 microRNAs were analyzed in nine plasma samples from HIV-1 infected individuals in the early phase of infection and three healthy controls using the miRNA PCR-array. Seventeen microRNAs were selected and validated in 80 plasma samples from HIV-1 infected individuals in the early phase of infection (20 each of eclipse stage, RNA+ stage, Ag + stage, and Ag + Ab+ stage of HIV-1 patients) and 25 healthy controls. Using the validation study results a plasma miRNA panel was developed and evaluated to detect early/acute HIV-1 infection in 49 blinded samples.

Finding: We identified an miRNA panel (P) containing four differentially expressed miRNAs (miR-16-5p, miR-20b-5p, miR-195-5p, and miR-223-3p) that could distinguish early HIV-1 infection from healthy controls with high AUC (1·000[1·00-1·00]), sensitivity (100%), and specificity (100%).We also found that miR-223-3p demonstrates 100% sensitivity and specificity (AUC 1·00[1·00-1·00]) and could distinguish eclipse stage of HIV-1 infection from healthy controls. To detect eclipse stage of HIV-1 infection we also developed a four-miRNA based (miR-16-5p, miR-206, let-7 g-3p, and miR-181c-3p) panel (P) with AUC 0·999 (0·995-1·000), 100% sensitivity and 95·8% specificity.

Interpretation: The miRNA panel, P is a potential biomarker for detecting early/acute stage of HIV-1infection and could help initiate early antiretroviral treatment, thus preventing the spread of HIV-1 infection.

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Source
http://dx.doi.org/10.1016/j.ebiom.2019.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557912PMC
May 2019
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