Epigenetic landscape in the kick-and-kill therapeutic vaccine BCN02 clinical trial is associated with antiretroviral treatment interruption (ATI) outcome

Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns

“…Furthermore, differences in the host epigenetic landscape exist between elite controllers and viraemic individuals, 35 , 36 and a recent study have observed that DNA methylation patterns are predictive for viral rebound after a kick-and-kill therapeutic intervention. 37 Additionally, DNA methylation levels of some ISGs such as PARP9 , IFI44L and EPSTI1 have been identified to be associated with mortality risk in participants of the Veterans Aging Cohort Study (VACS). 38 All these data suggest that the epigenetic modulation of ISGs and other host genes may play an essential role in HIV pathogenesis.…”

DNA Vaccines: Their Formulations, Engineering and Delivery

“…Vaccines have been shown to have heterologous, or ‘non-specific’ effects, which are additional effects beyond the specific protection against the targeted disease [ 110 , 111 , 112 ]. While the exact mechanisms are only beginning to be understood, there is emerging evidence that epigenetic mechanisms are involved [ 113 ], including DNA imprinting, as has been shown in HIV and BCG vaccine patient analyses [ 114 , 115 ]. The data from the BCG cohorts indicates that many of these ‘non-specific’ effects can be especially useful, having proven benefit in protecting against autoimmune diseases including multiple sclerosis and type 1 diabetes.…”

HIV cure trial mergers: Spotlighting the epigenetics of latency reversal

“…In this issue of eBioMedicine , Oriol-Tordera et al have taken a unique and clever approach to help tackle this limitation. 5 Their new manuscript merges data from two distinct interventional clinical trials where the single-arm BCN02 study (NCT02616874) is the “experimental arm” and the single-arm REDUC study (NCT02092116) is the “control arm”. 6 , 7 This merging of trials is not implying that BCN02 and REDUC are perfectly matched trials.…”

“…In the new manuscript, the REDUC samples serve as a surrogate romidepsin-only control arm for the transcriptomics and whole-genome DNA methylation analyses presented. 5 Inclusion of the romidepsin-only controls helps to disentangle the effects of the romidepsin intervention from the impacts of the vaccination regimen utilized in the BCN02 study.…”

“…One such broad pattern was that hypomethylation in regions of repressed chromatin at the time of intervention was associated with delayed viral rebound following antiretroviral treatment interruption. 5 It remains to be seen whether the described methylation signatures can be used prospectively to predict antiretroviral therapy interruption outcomes.…”