Longitudinal Changes in Epigenetic Age Acceleration in Aviremic Human Immunodeficiency Virus-Infected Recipients of Long-term Antiretroviral Treatment

J Infect Dis. 2022 Jan 18;225(2):287-294. doi: 10.1093/infdis/jiab338.


Background: Human immunodeficiency virus (HIV) infection induces epigenetic age acceleration (EAA), but it remains unclear whether epigenetic aging continues to accelerate during successful antiretroviral therapy (ART) and prolonged virological suppression.

Methods: We longitudinally analyzed 63 long-term aviremic HIV-infected adults. Using blood DNA methylation patterns, we calculated EAA measures based on 3 epigenetic clocks (Horvath's clock, PhenoAge, and GrimAge). We recorded the emergence of serious AIDS-related and non-AIDS-related events throughout the study to assess its association with EAA.

Results: All participants were on stable ART and were virologically suppressed. After 4 years of follow-up, PhenoAge-EAA and GrimAge-EAA showed no differences, whereas Horvath-EAA slightly decreased (median difference, -0.53 years; P = .015). Longitudinal changes in EAA measures were independent of changes in CD4 cell counts, the ART regimen, or other HIV-related factors. Nineteen percent of participants experienced a serious clinical event during the study. Horvath-EAA was significantly higher at baseline in participants with clinical events (P = .027). After adjusting for confounders, we found a trend toward an association of higher levels of all EAA measures at baseline with serious clinical events.

Conclusions: Epigenetic aging did not accelerate in long-term aviremic HIV-infected adults after 4 years of successful ART. EAA measures deserve further study as potential tools for predicting clinical events.

Keywords: HIV infection; aging; antiretroviral therapy; epigenetic age acceleration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / genetics*
  • Anti-Retroviral Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / methods*
  • Epigenesis, Genetic*
  • Epigenomics
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged


  • Anti-Retroviral Agents