Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART
Abstract
HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 13, 2021
- Source ID
- 10.1371/journal.ppat.1009785
Entities
People
- Alina P.S. Pang
- Andrew C. Belden
- Carlo Sacdalan
- Denise Hsu
- Donn Colby
- Eugène Kroon
- Kyu S. Cho
- Lishomwa Ndhlovu
- Merlin L Robb
- Michael J. Corley
- Nisakorn Ratnaratorn
- Nitiya Chomchey
- Robert Paul
- Sandhya Vasan
- Serena Spudich
- The Search010/rv254 And Search013/rv304 Study Groups
- Victor G Valcour
Organizations
- Gilead Sciences
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Merck & Co.
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Mental Health
- United States Department of Defense
- ViiV Healthcare