Guinevere Q. Lee

In this session, four speakers presented: a new class of latency reversal agent, the efficacy of DART in mice and safety data in human, the efficacy of combined SMAC mimetic and antibodies in macaques, and considerations when using the latest FDA-approved attachment inhibitor fostemsavir in cure-related studies.

Marion Pardons (HIV Cure Research Center, Belgium) presented a novel HIV latency reversal compound Tat#1 which mimics HIV transcription-transactivator Tat. Unlike existing classes of latency reversal agents which alter host transcriptome profiles, Tat#1 did not significantly alter the host transcription profiles upon treatment, reactivates HIV, and did not impact cell viability. Jeffrey Nordstrom (MacroGenics Inc.) presented mice and human phase 1 trial data on DART molecules MGD014 (A32) and/or MGD020 (7B2). Treatment reduced cell-associated viral RNA and delayed viral rebound in mice, and in human was safe and serum levels was above the in vitro half maximal effective concentration (EC50) and did not activate T cells. Amir Dashti (Emory) showed that latency reversal agent AZD5582 was able to active SIV RNA production in 100% of treated macaques and the extent of on-treatment viremia directly correlated with pre-therapy viral load, and when combined with antibodies treatment reduced SIV DNA load in tissue and blood. Marianne Boutin (Université de Montréal) showed that temsavir, the active metabolite of a recently FDA-approved ARV fostemsavir (FTR), impacted Env conformation at the surface of virions and infected cells, and reduced the capacity of bnAbs to mediate ADCC, which should be considered if used in cure-related studies.

New methods and combinations of methods are being actively evaluated in cure research. This session showcased promising new approaches to target the reservoir via “shock and kill.” Understanding the strength and limitations of each new technology is key to designing effective strategies in future studies.