A Phase 1/2 Randomized, Placebo-Controlled Trial Of Romidespin In Persons With Hiv-1 On Suppressive Antiretroviral Therapy

Background. Romidepsin (RMD) is a histone deacetylase inhibitor reported to reverse HIV-1 latency. We sought to identify doses of RMD that were safe and induced HIV-1 expression.Methods. Enrollees had HIV-1 RNA <40 copies/mL on antiretroviral therapy. Measurements included RMD levels, plasma viremia by single-copy HIV-1 RNA assay, HIV-1 DNA, cell-associated unspliced HIV-1 RNA (CA-RNA), acetylation of histone H3-lysine-9 (H3K9ac(+)), and phosphorylation of transcription factor P-TEFb. Wilcoxon tests were used for comparison.Results. In the single-dose cohorts 1-3, 43 participants enrolled (36 participants 0.5, 2, 5 mg/m(2) RMD; 7 placebo) and 16 enrolled in the multidose cohort 4 (13 participants 5 mg/m(2) RMD; 3 placebo). One grade 3 event (neutropenia) was possibly treatment related. No significant changes in viremia were observed in cohorts 1-4 compared to placebo. In cohort 4, pharmacodynamic effects of RMD were reduced proportions of CD4(+) T cells 24 hours after infusions 2-4 (median, -3.5% to -4.5%) vs placebo (median, 0.5% to 1%; P <= .022), and increased H3K9ac(+) and phosphorylated P-TEFb in CD4 (+) T cells vs placebo (P <= .02).Conclusions. RMD infusions were safe but did not increase plasma viremia or unspliced CA-RNA despite pharmacodynamic effects on CD4(+) T cells.