The Depsipeptide Romidepsin Reverses HIV-1 Latency in Vivo

Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (art) has been proposed as a step towards curing hiv-1 infection. however,until now,approaches to reverse hiv-1 latency in humans have yielded mixed results. here,we report a proof-of-concept phase ib/iia trial where 6 aviremic hiv-1 infected adults received intravenous 5 mg/m2 romidepsin (celgene) once weekly for 3 weeks while maintaining art. lymphocyte histone h3 acetylation,a cellular measure of the pharmacodynamic response to romidepsin,increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. concurrently,hiv-1 transcription quantified as copies of cell-associated un-spliced hiv-1 rna increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03). plasma hiv-1 rna increased from <20 copies/ml at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/ml following the second infusion,p = 0.04). importantly,romidepsin did not decrease the number of hiv-specific t cells or inhibit t cell cytokine production. adverse events (all grade 1–2) were consistent with the known side effects of romidepsin. in conclusion,romidepsin safely induced hiv-1 transcription resulting in plasma hiv-1 rna that was readily detected with standard commercial assays demonstrating that significant reversal of hiv-1 latency in vivo is possible without blunting t cell-mediated immune responses. these finding have major implications for future trials aiming to eradicate the hiv-1 reservoir. trial registration: clinicaltrials.gov ntc02092116 © 2015 søgaard et al.