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MicroRNAs (miRNAs/miRs) may serve as therapeutic agents or targets in diseases in which the expression of proteins plays an important role. The aim of the present study was to compare the expression levels of specific miRNAs, as well as their correlation with markers of response to antiretroviral (ARV) therapy, in patients with human immunodeficiency virus type 1 (HIV-1) infection with and without resistance to highly active antiretroviral therapy (HAART). Methods: miRNA assays were performed on plasma samples obtained from 20 HIV-1-positive patients. A total of ten patients were divided into two groups: HAART-responsive and HAART-resistant (n=5 per group). Commercial arrays were subsequently used to identify 84 miRNAs. A total of three differentially expressed miRNAs were selected and analyzed by quantitative PCR (qPCR). Five other patients were subsequently added to each group for a new relative expression analysis. The absolute expression level of the two miRNAs was obtained and compared using the Student’s t test. Receiver operating characteristic (ROC) curves were used to identify patients with antiretroviral therapy (ART) resistance. Results: The array analysis revealed that miR-15b-5p, miR-16-5p, miR-20a-5p, miR-26a-5p, miR-126-3p and miR-150-5p were down-regulated in patients with HAART-resistance comparing with HAART-responsive. The expression levels of miR-16-5p, miR-26a-5p and miR-150-5p were confirmed using qPCR. The area under the ROC curve was 1.0 for the three miRNAs. Conclusions: The lower expression levels of miR-16-5p and miR-26a-5p in patients with HAART-resistance suggested that these may serve as potential biomarkers for the identification of HAART-responsive patients.

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.

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HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain–blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer’s and Parkinson’s disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.

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