A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

Consumers and Carers Versus Pharmacy Staff: Do Their Priorities for Australian Pharmacy Services Align?

Background Health professionals, including pharmacists, are encouraged to meet the needs of their consumers in an efficient and patient-centred manner. Yet, there is limited information as to what consumers with chronic conditions need from pharmacy as a healthcare destination or how well pharmacy staff understand these needs. Objective The aim of this study was to identify service user priorities for ideal community pharmacy services for consumers with chronic conditions and their carers, and compare these priorities with what pharmacy staff think these groups want. Methods The nominal group technique was undertaken with pharmacist, pharmacy support staff, consumer and carer groups in four Australian regions between December 2012 and April 2013. Participant ideas and priorities for ideal services or care were identified, and contextual insight was obtained by thematic analysis. Results Twenty-one nominal group sessions are accepted, including 15 consumer and carer, four pharmacist and two pharmacy support staff groups. Pharmacy staff views generally aligned with consumer priorities, such as access, affordability, patient-centred care and continuity and coordinated care, yet diverged with respect to consumer information or education on medication and services. Fundamentally, consumers and carers sought streamlined access to information and medication, in a coordinated, patient-centred approach. Alleviating financial burden was a key consumer priority, with a call for the continuation and extension of medication subsidies. Conclusion Overall, pharmacy staff had a reasonable understanding of what consumers would prioritise, but further emphasis on the importance, delivery, or both, of consumer information is needed. Greater consideration is needed from policy makers regarding the financial barriers to accessing medication for consumers with chronic conditions