Romidepsin (RMD) is a histone deacetylase inhibitor (HDACi) able to induce HIV transcription in vitro and in vivo. Its effects on the brain during cure strategies are unknown. We investigated cognitive, neuroimaging, and functional outcomes in the BCN02-Romi Study, a trial that assessed the effects of an HIVconsv vaccine in combination with RMD in early-treated HIV-infected persons (clinicaltrials.gov: NCT02616874).
The BCN02-Romi Study tested a kick&kill strategy that combined 2 administrations of an HIVconsv vaccine (pre and post RMD, weeks 0 and 9), with 3 weekly infusions of RMD (5mg/m2; weeks 3, 4, and 5), a monitored antiretroviral pause (MAP, starting at week 17), and a 24-week period after the reinitiation of cART. Inclusion in the BCN02-Neuro Substudy was offered to the 15 individuals recruited in the BCN02-Romi Study and 11 accepted to participate (Intervention Group, IG, n=11). Early-treated but not vaccinated individuals were recruited as controls (Control Group, CG, n=10). CNS assessments were performed before RMD administration (Pre), after final RMD administration (Post), and after MAP + 24-week cART reinitiation (Final). Study variables comprised cognitive functioning (NPZ6), 3T magnetic resonance imaging (voxel-wise whole-brain structural changes), and functional outcomes (daily functioning, adverse events, and emotional symptoms). Study endpoints were based on between-arm differences in change from Pre to Post and Final assessments.
Global cognitive functioning was comparable between groups at the 3 study timepoints (mean NPZ6 [SD]): Pre: IG: 0.28 (0.64), CG: 0.28 (0.63), p=0.98; Post: IG: 0.42 (0.54), CG: 0.31 (0.61), p=0.66; Final: IG: 0.41 (0.59), CG: 0.55 (0.76), p=0.69. Analysis of change confirmed these results (mean NPZ6 change [SD]): Post: IG: 0.13 (0.31), CG: 0.03 (0.32), p=0.45; Final: IG: 0.15 (0.43), CG: 0.27 (0.35), p=0.56. Neuroimaging analyses did not find differences between groups at any timepoint (all p values >0.10). No differences were also observed in daily functioning outcomes, CNS adverse events, or emotional symptoms.
No detrimental effects of a kick&kill strategy with RMD were observed on cognitive functioning, neuroimaging, or functional outcomes in this small study. The HIV cure approach investigated, including the use of an HIVconsv vaccine, administration of RMD, and cART interruption with posterior 24-week therapy reinitiation, appears to be safe for the brain.