Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years.
Level 3 - non-randomized controlled study
Longitudinal cohort study with repeated within-subject follow-up across untreated and treated disease phases.
PubMed 37148893 · doi:10.1016/S2666-7568(23)00037-5
What was done
In a 17-year longitudinal study within the Swiss HIV Cohort Study, researchers evaluated epigenetic ageing in 80 people with HIV across four time points (T1 to T2 separated by ≥3 years of untreated infection; T3 to T4 separated by ≥3 years of suppressive antiretroviral therapy [ART]). Epigenetic age acceleration (EAA) and ageing rates were assessed in peripheral blood mononuclear cells (PBMCs) using five epigenetic clocks: Horvath, Hannum, SkinBlood, PhenoAge, and GrimAge.
What was found
During untreated HIV infection (median observation 8.08 years), mean annual EAA increased by 0.47 years (95% CI 0.37 to 0.57) for Horvath, 0.43 years (0.30 to 0.57) for Hannum, 0.36 years (0.27 to 0.44) for SkinBlood, 0.69 years (0.51 to 0.86) for PhenoAge, and 0.10 years (0.02 to 0.19) for GrimAge, corresponding to total ageing of 1.36–1.69 biological years per calendar year for the first four clocks. During suppressive ART (median observation 9.8 years), mean annual EAA decreased by -0.35 years (-0.44 to -0.27) for Horvath, -0.39 years (-0.50 to -0.27) for Hannum, -0.26 years (-0.33 to -0.18) for SkinBlood, -0.49 years (-0.64 to -0.35) for PhenoAge, and -0.05 years (-0.12 to 0.02) for GrimAge, corresponding to 0.51–0.74 biological years per calendar year. HIV-related, antiretroviral, immunological variables, and a polygenic risk score contributed minimally to EAA.
Why it matters
This study provides long-term within-individual evidence that untreated HIV infection accelerates biological ageing, whereas sustained viral suppression on ART decelerates it, emphasizing the importance of prompt and continuous ART initiation.
Limits
The sample size was modest (80 participants) and demographically homogenous (65% male, 95% White), limiting generalizability. There was no HIV-negative comparator group. Epigenetic ageing was assessed only in PBMCs, which may not capture tissue-specific epigenetic dynamics.
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- supports HIV-positive individuals exhibit 5 to 7 years of epigenetic age acceleration in blood, which is reversed by 4 to 5 years following antiretroviral therapy.