Improving HIV Surveillance Data for Public Health Action in Washington, DC: A Novel Multiorganizational Data-Sharing Method

Background: The National HIV/AIDS Strategy calls for active surveillance programs for human immunodeficiency virus (HIV) to more accurately measure access to and retention in care across the HIV care continuum for persons living with HIV within their jurisdictions and to identify persons who may need public health services. However, traditional public health surveillance methods face substantial technological and privacy-related barriers to data sharing. Objective: This study developed a novel data-sharing approach to improve the timeliness and quality of HIV surveillance data in three jurisdictions where persons may often travel across the borders of the District of Columbia, Maryland, and Virginia. Methods: A deterministic algorithm of approximately 1000 lines was developed, including a person-matching system with Enhanced HIV/AIDS Reporting System (eHARS) variables. Person matching was defined in categories (from strongest to weakest): exact, very high, high, medium high, medium, medium low, low, and very low. The algorithm was verified using conventional component testing methods, manual code inspection, and comprehensive output file examination. Results were validated by jurisdictions using internal review processes. Results: Of 161,343 uploaded eHARS records from District of Columbia (N=49,326), Maryland (N=66,200), and Virginia (N=45,817), a total of 21,472 persons were matched across jurisdictions over various strengths in a matching process totaling 21 minutes and 58 seconds in the privacy device, leaving 139,871 uniquely identified with only one jurisdiction. No records matched as medium low or low. Over 80% of the matches were identified as either exact or very high matches. Three separate validation methods were conducted for this study, and they all found ≥90% accuracy between records matched by this novel method and traditional matching methods. Conclusions: This study illustrated a novel data-sharing approach that may facilitate timelier and better quality HIV surveillance data for public health action by reducing the effort needed for traditional person-matching reviews without compromising matching accuracy. Future analyses will examine the generalizability of these findings to other applications

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 \u27ALT-803\u27, 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