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Significance The latent reservoir for HIV-1 is a major barrier to curing the infection. Current cure strategies are focused on eliminating the reservoir through a two-step “shock and kill” approach involving the use of small-molecule latency-reversing agents (LRAs) followed by immune interventions to kill infected cells. Numerous candidate LRAs have been identified in studies using in vitro models of latency, but none have been shown to reduce the reservoir in vivo. We show here that many candidate LRAs work through an unexpected pathway involving the transcription factor HSF1, a result with implications for developing effective combinations of LRAs for use in HIV cure strategies.

HSF1 inhibition attenuates HIV-1 latency reversal mediated by several candidate LRAs In Vitro and Ex Vivo