Identification of a circulating long non-coding RNA signature panel in plasma as a novel biomarker for the detection of acute/early-stage HIV-1 infection

• Published in: Biomarker research 2024-06, Vol.12 (1), p.61-15, Article 61
• Main Authors: Biswas, Santanu, Nagarajan, Namrata, Hewlett, Indira, Devadas, Krishnakumar
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Acute HIV-1; AIDS; Analysis; Antibodies; Antigens; Antiretroviral therapy; Antiviral agents; ART HIV-1; Biomarkers; Cardiovascular disease; Disease transmission; Drug resistance; Early HIV-1; Ethylenediaminetetraacetic acid; Health aspects; Hepatitis; Highly active antiretroviral therapy; HIV; HIV (Viruses); HIV testing; Human immunodeficiency virus; Immunoassay; Infections; Life sciences; Medical research; Medicine, Experimental; Non-coding RNA; Plasma; Plasma lncRNA biomarker and diagnosis; RNA; Seroconversion; Therapeutic targets
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-024-00597-7

Individuals with acute / early HIV-1 infection are often unaware that they are infected with HIV-1 and may be involved in high-risk behavior leading to transmission of HIV-1. Identifying individuals with acute / early HIV-1 infection is critical to prevent further HIV-1 transmission, as diagnosis can lead to several effective HIV-1 prevention strategies. Identification of disease-stage specific non-viral host biomarkers would be useful as surrogate markers to accurately identify new HIV-1 infections. The goal of this study was to identify a panel of host derived plasma long non-coding RNAs (lncRNAs) that could serve as prognostic and predictive biomarkers to detect early/acute HIV-1 infection. A total of 84 lncRNAs were analyzed in sixteen plasma samples from HIV-1 infected individuals and four healthy controls using the lncRNA PCR-array. Twenty-one lncRNAs were selected and validated in 80 plasma samples from HIV-1 infected individuals [HIV-1 infected patients in the eclipse stage (n = 20), acute stage (n = 20), post-seroconversion p31 negative stage (n = 20), and post-seroconversion p31 positive stage (n = 20) of infection] and 20 healthy controls. The validation study results were used to develop a plasma lncRNA panel that was evaluated in the panel test phase to detect early/acute HIV-1 infection in 52 independent samples. We identified a lncRNA panel (P ) containing eight lncRNAs (DISC2, H19, IPW, KRASP1, NEAT1, PRINS, WT1-AS and ZFAS1) that could distinguish HIV-1 infection from healthy controls with high AUC 0·990 (95% CI 0.972-1.000), sensitivity (98.75%), and specificity (95%). We also found that P and P demonstrates 100% sensitivity and specificity (AUC 1·00; 95%CI:1·00-1·00) and could distinguish eclipse stage and acute stage of HIV-1 infection from healthy controls respectively. Antiretroviral treatment (ART) cumulatively restored the levels of lncRNAs to healthy controls levels. lncRNA expression changes significantly in response to HIV-1 infection. Our findings also highlight the potential of using circulating lncRNAs to detect both the eclipse and acute stages of HIV-1 infection, which may help to shorten the window period and facilitate early detection and treatment initiation. Initiating ART treatment at this stage would significantly reduce HIV-1 transmission. The differentially expressed lncRNAs identified in this study could serve as potential prognostic and diagnostic biomarkers of HIV-1 infection, as well as new therapeutic targets.