How Acceptable Is A Wireless Pill Bottle That Monitors and Texts In Response To Missed Doses: Focus Groups With Young African American MSM Living With HIV

Abstract Background African American MSM (AAMSM) living with HIV are less likely to have viral suppression than other racial groups. Wisepill, a wireless pill bottle, transmits a cellular signal to a server when opened and is designed to measure antiretroviral therapy (ART) adherence. The objective of this study was to explore the acceptability of a proposed intervention in these young AAMSM using the Wisepill device opening data to trigger a real-time text alert that ART may not have been taken during a planned time to either the user, a trusted social contact, or a healthcare worker, depending on the duration of consecutively missed doses (1 dose, 3 doses, 7 doses, respectively). Methods From December 2016 – May 2017, AAMSM living with HIV age 18–34 years (N = 25) participated in a study that included five focus groups (n = 23) and one on one interviews (n = 2). We performed theory-based discussion grounded in the Technology Acceptance Model. Specifically, we explored usefulness, convenience, concerns, and intention to use. Results Fifty-two percent missed at least one dose in the 4 days prior to the focus group meeting. Almost all participants (94%) favored the idea of a wireless pill bottle monitor and linked text message notification that ART may have been missed. The device was considered convenient for use at home or in a backpack, but too large for a pocket. Stigma and privacy were common concerns. For example, participants did not want to carry the device with them if the pills would “sound like a walking pharmacy” and did not want a text message that said, “You missed your HIV meds.” They preferred text message notifications that ranged from emoji icons to cryptic short texts and wanted to receive an email as a backup plan. Most believed that the device appearance would not gain unwanted attention. Thirty percent of the participants identified a partner as a social contact to whom the 3-day missed dose reminders would be sent whereas others designated their mother, aunt, brother, friend, pastor, and case-manager. Conclusion An adherence intervention using a wireless pill bottle monitoring device linked to text notifications was acceptable to most of the young AAMSM in this study. Acceptability may be enhanced by personalization of the responsive text messages and a backup email option. Disclosures J. E. Haberer, Merck: Consultant, Consulting fee; Natera: Shareholder, Stock ownershi

A triaged real-time alert intervention to improve antiretroviral therapy adherence among young African American men who have sex with men living with HIV: focus group findings

Abstract Background Among persons living with HIV, poorer antiretroviral therapy adherence has been reported in African Americans and disproportionate mortality reported in young African American men who have sex with men (AAMSM) compared to whites. We report the results of focus groups with young AAMSM living with HIV that explore their opinions about the acceptability and feasibility of a triaged real-time missed dose alert intervention to improve treatment adherence. The purpose of this study is to develop a theory-driven triaged real-time adherence monitoring intervention to promote HIV medication adherence in young AAMSM. Methods We performed five focus groups and two individual interviews among young HIV-positive AAMSM (n = 25) in Chicago guided by the Technology Acceptance Model and explored perceptions regarding the monitoring concept including device issues and concerns about inclusion of support persons whose involvement is triggered by sustained missed doses. The purpose was to inform the development of this intervention in this population. Results Generally, the participants found the proposed intervention acceptable and useful. Privacy was a major concern for participants especially with attention to possible disclosure of their HIV status by receiving a medication-related text that someone else might view and could lead to unwanted attention. There was concern that the device could be confused with a taser. Approximately half of the men already had a close personal contact that helped them with medication taking. Some participants acknowledged that the notification might lead to friction. Conclusions A triaged real-time alert intervention to improve treatment adherence is acceptable and feasible among young AAMSM living with HIV

Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders

Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology

Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation

Abstract Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks

Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia.

The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted