Emerging role of LncRNAs MMP2-AS1, FAM222A-AS1, and XIST as potential biomarkers in HIV patients receiving antiretroviral therapy

Long non-coding RNAs (lncRNAs) play crucial roles in immune regulation and viral pathogenesis. However, their expression patterns and clinical relevance in HIV infection remain incompletely understood. This study aimed to validate differentially expressed lncRNAs in HIV-infected individuals and evaluate their potential roles in distinguishing viremic and ART-suppressed patients. Transcriptomic analysis was performed on the GSE235038 dataset from the gene expression omnibus. Differentially expressed lncRNAs were identified using GEO2R (log₂FC > 2/< −2, p < 0.05). lncRNAs MMP2-AS1, FAM222A-AS1, and XIST were experimentally validated in a Pakistani clinical cohort (195 HIV patients and 51 healthy controls) using quantitative real-time PCR. ROC curve analysis was used to assess the diagnostic performance of lncRNAs. Competing endogenous RNA (ceRNA) networks were constructed, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. Significant lncRNA dysregulation was observed associated with HIV infection and ART status. MMP2-AS1 was upregulated in viremic patients, whereas FAM222A-AS1 and XIST were markedly downregulated. qRT-PCR validation confirmed these expression patterns. MMP2-AS1 and FAM222A-AS1 exhibited strong diagnostic performance in distinguishing viremic patients from healthy controls, XIST showed high discriminatory ability suggesting a potential association with treatment response. ceRNA network analysis revealed interactions with immune and signaling pathways related to miRNAs and mRNAs. Functional enrichment highlighted pathways involved in immune regulation, transcriptional control, and signal transduction. Distinct lncRNAs expression is associated with HIV disease activity and ART response. MMP2-AS1 and FAM222A-AS1 show potential as diagnostic biomarkers, while XIST may serve as a treatment-response–associated marker. However, interpretation of XIST requires consideration of its sex-specific expression and validation in balanced cohorts.