Candidate host epigenetic marks predictive for HIV reservoir size, responsiveness to latency reversal, and viral rebound.
AIDS
; 35(14): 2269-2279, 2021 11 15.
Article
en En
| MEDLINE
| ID: mdl-34482353
ABSTRACT
OBJECTIVE:
This study aimed to identify candidate host epigenetic biomarkers predicting latency reversal agents (LRA) efficacy and HIV-1 rebound kinetics during analytical treatment interruption (ATI).DESIGN:
Retrospective longitudinal epigenetic profiling study from 13 people with HIV (PWH) on virologically suppressive antiretroviral therapy (ART) that participated in a LRA (HDAC inhibitor) clinical trial (NCT01680094) and a subsequent optional ATI to monitor for viral recrudescence after ART cessation.METHODS:
Genome-wide DNA methylation (DNAm) in purified CD4+ T cells was measured at single-nucleotide resolution using the Infinium MethylationEPIC array. HIV-1 DNA and RNA measures were previously assessed by PCR-based methods and the association of DNAm levels at regulatory sites of the human genome were examined with reservoir size, responsiveness to LRA, and time to viral rebound following ATI.RESULTS:
A distinct set of 15 candidate DNAm sites in purified CD4+ T cells at baseline pre-LRA and pre-ATI significantly correlated with time to viral rebound. Eight of these DNAm sites occurred in genes linked to HIV-1 replication dynamics including (SEPSECS, cg19113954), (MALT1, cg15968021), (CPT1C, cg14318858), (CRTAM, cg10977115), (B4GALNT4, cg04663285), (IL10, cg16284789), (TFPI2, cg19645693), and (LIFR, cg26437306); with the remaining sites at intergenic regions containing regulatory elements. Moreover, baseline DNAm states related to total HIV-1 DNA levels and the fold change in unspliced cell-associated HIV RNA following LRA treatment.CONCLUSION:
Preexisting host epigenetic states may determine HIV-1 rebound kinetics and reservoir maintenance. These findings suggest integrating a suite of DNA methylation markers to improve optimal participant selection and drug regimen in future HIV cure clinical trials.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2021
Tipo del documento:
Article