Acceptability of a Patient Portal (Opal) in HIV Clinical Care: A Feasibility Study.

Opal (opalmedapps.com), a patient portal in use at the Cedars Cancer Centre of the McGill University Health Centre (MUHC) (Montreal, Canada), gives cancer patients access to their medical records, collects information on patient-reported outcome measures (PROMs), and has demonstrated patient satisfaction with care. This feasibility study aims to evaluate Opal's potential acceptability in the context of HIV care. People living with HIV (PLWH) and their healthcare providers (HCPs) completed cross-sectional surveys from August 2019 to February 2020 at large HIV centers, including the Chronic Viral Illness Service of the MUHC, and other HIV clinical sites in Montreal and Paris, France. This study comprised 114 PLWH (mean age 48 years old, SD = 12.4), including 74% men, 24% women, and 2% transgender or other; and 31 HCPs (mean age 46.5 years old, SD = 11.4), including 32% men, 65% women, and 3% other. Ownership of smartphones and tablets was high (93% PLWH, 96% HCPs), and participants were willing to use Opal (74% PLWH, 68% HCPs). Participants were interested in most Opal functions and PROMs, particularly PROMs capturing quality of life (89% PLWH, 77% HCPs), experience of healthcare (86% PLWH, 97% HCPs), and HIV self-management (92% PLWH, 97% HCPs). This study suggests Opal has high acceptability and potential usefulness as perceived by PLWH and HCPs.

The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection.

BACKGROUND: IL-37 is a member of the IL-1 family with potent anti-inflammatory effects. Little is known about regulation of the cytokine and of its signaling co-receptor SIGIRR in HIV infection. OBJECTIVES: Our main objective was to investigate how production of the cytokine and expression of SIGIRR on immune cells is regulated in HIV infection. METHODS: The study was conducted using biological samples from a cross section of HIV-infected individuals. Concentrations of IL-37, TNF-α and soluble form of SIGIRR in serum samples were determined by ELISA. The expression of SIGIRR on immune cells was determined by flow cytometry. IL-37 isoform-specific transcripts were determined in PBMC by RT-PCR using isoform-specific primers. The effects of exogenous IL-37 on HIV replication in human phytohaemagglutinin (PHA) blasts were determined in in-vitro assays. RESULTS: The cytokine concentrations tended to decrease in treatment-naive HIV-infected individuals. They were higher in treated HIV-infected individuals compared with those from treatment-naive ones. Higher concentrations of the cytokine were observed in sera from LTNP. The expression of SIGIRR on immune cells was decreased in HIV-infected individuals. On the other hand, its soluble form increased in the sera in these individuals. The trend was reversed in the patients undergoing antiretroviral treatment. Soluble SIGIRR attenuated anti-inflammatory effects of the cytokine. Serum IL-37 and soluble SIGIRR concentrations correlated with certain clinical parameters of the patients. Furthermore, recombinant human IL-37 inhibited HIV replication in human PHA blasts. CONCLUSION: The IL-37/SIGIRR axis is functionally compromised in HIV-infected individuals. Targeting the axis may alleviate inflammation and decrease HIV replication in this viral infection.

A protective role of IL-37 in cancer: a new hope for cancer patients.

IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes. Both precursor and cleaved forms of IL-37 are secreted. They bind IL-18Rα chain (also used by IL-18 as a receptor subunit) and recruit Toll/IL-1R (TIR)-8 for transducing intracellular signaling. TIR-8 is a member of the IL-1 receptor family (IL-1RF) and was previously known as an orphan receptor. IL-37 suppresses activation of NF-κB and MAPK and activates Mer-PTEN-DOK pathway. It negatively regulates signaling mediated by TLR agonists, proinflammatory cytokines, and IL-1RF ligands. It also affects cell metabolism by inhibiting mTOR, GSK-3α/ß, and activating AMPK. Despite having the ability to dampen host's immune responses, the cytokine has been shown to exert antitumor effects, and it has been suggested that it may act as a prognostic marker in a variety of human cancers. Recent studies have suggested that IL-37 may represent a novel therapeutic tool in patients with cancer. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its anti-cancer effects, and suggest guidelines for future research.