Missed Opportunities When We Focus only on Risk: Using the Concerns Based Conversation Starter to Identify Potential PrEP Candidates.

Collection and use of self-reported HIV sexual risk-behaviors to identify pre-exposure prophylaxis (PrEP) candidates is common practice in PrEP providing and referral services. Critiques of this strategy highlight overreliance on self-report and contribution to ongoing PrEP stigma. As an alternative (or complimentary) approach, we evaluated a 5-item Concerns Based Conversation Starter (CBCS) that could be used to identify individuals who could benefit from PrEP. The CBCS was included in the 2019 cycle of the American Men's Internet Survey. Item responses were characterized overall and in relation to CDC risk-based PrEP indication and reported willingness to use PrEP. In total, 1606 HIV-negative men who have sex with men not on PrEP were evaluated. Of these, 50% were below the age of 25, 11% Black, 16% Latino, and 64% White. Across the sample, 61% (986) met risk-based criteria for PrEP indication, 80% (1278) were identified by the CBCS, and 52% (835) were flagged by both. The CBCS uniquely identified 28% (443) for follow-up PrEP discussions that would have been missed by a risk-based only approach. Only 9% (151) of the sample had risk-based indication but did not report concerns. Over half of those flagged by the CBCS expressed willingness to use PrEP. The CBCS identified more people than a risk-based indication approach, with most also reporting an interest in using PrEP. A small percentage of risk-indicated participants were 'missed' by the CBCS. As PrEP options and access points expand, implementation tools like the CBCS can facilitate more wide-scale, values-focused PrEP implementation.

Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells.

The E3 ubiquitin ligase Cbl-b has been characterized as an intracellular checkpoint in T cells; however, the function of Cbl-b in primary human NK cells, an innate immune anti-tumor effector cell, is not well defined. In this study, we show that the expression of Cbl-b is significantly upregulated in primary human NK cells activated by IL-15, IL-2, and the human NK cell-sensitive tumor cell line K562 that lacks MHC class I expression. Pretreatment with JAK or AKT inhibitors prior to IL-15 stimulation reversed Cbl-b upregulation. Downregulation of Cbl-b resulted in significant increases in granzyme B and perforin expression, IFN-γ production, and cytotoxic activity against tumor cells. Collectively, we demonstrate upregulation of Cbl-b and its inhibitory effects in IL-15/IL-2/K562-activated human NK cells, suggesting that Cbl-b plays a negative feedback role in human NK cells.