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Effect of Pitavastatin on Epigenetic Aging Biomarkers in People With HIV: Pilot Substudy of the REPRIEVE Trial
Michael J Corley1, Maya Watanabe2, Alina P S Pang1
1Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
Insights
Pitavastatin may slow biological aging in people with HIV (PWH). The REPRIEVE trial found pitavastatin prevented an increase in the pace of aging over 24 months, unlike placebo. Further research is recommended.
Area of Science:
- Epigenetics
- Gerontology
- Immunology
Background:
- People with HIV (PWH) experience accelerated biological aging and increased cardiovascular disease (CVD) risk.
- The REPRIEVE trial showed pitavastatin reduced cardiovascular events in PWH on antiretroviral therapy (ART).
- The effect of statin therapy on epigenetic aging in PWH remains unclear.
Purpose of the Study:
- To investigate whether pitavastatin can modulate epigenetic aging in PWH.
- To assess changes in epigenetic aging biomarkers over 24 months in PWH receiving pitavastatin or placebo.
Main Methods:
- DNA methylation profiles from peripheral blood mononuclear cells (PBMCs) were analyzed in 99 REPRIEVE participants.
- Epigenetic aging was measured using PCGrimAge and DunedinPACE clocks.
- Changes in epigenetic age were compared between the pitavastatin and placebo groups over 24 months.
Main Results:
- All participants exhibited epigenetic age acceleration at baseline.
- While PCGrimAge did not differ significantly between groups, DunedinPACE (pace of aging) increased in the placebo arm but not the pitavastatin arm.
- A significant difference in the change of DunedinPACE was observed between the pitavastatin and placebo groups (P = .049).
Conclusions:
- This pilot study suggests that pitavastatin may prevent an increase in the biological pace of aging in PWH.
- Epigenetic age acceleration is prevalent in PWH at trial entry.
- Further research is warranted to explore statin therapy as an intervention for accelerated aging in PWH.
Background:
People with human immunodeficiency virus (HIV, PWH) exhibit increased cardiovascular disease (CVD) risk and accelerated biological aging. REPRIEVE demonstrated that pitavastatin reduced major adverse cardiovascular events (MACE) in antiretroviral therapy (ART)-treated PWH with low-to-moderate traditional cardiovascular risk. It remains unknown whether statin therapy can modulate epigenetic aging in PWH.
Methods:
We assessed epigenetic aging biomarkers using DNA methylation profiles from peripheral blood mononuclear cells (PBMCs) in a subset of 99 randomly selected US REPRIEVE participants (65 pitavastatin, 34 placebo) at baseline and 24 months. The primary outcomes were changes in second- and third-generation epigenetic clocks PCGrimAge (trained on mortality risk) and DunedinPACE (trained on rate of age-related multi-organ decline).
Results:
Median chronological age was 57.0 (Q1, Q3: 56, 58) years and 100% of participants demonstrated epigenetic age acceleration, measured by the difference in PCGrimAge and chronological age (median difference 7.08 years [Q1, Q3: 4.69, 9.64]) at entry. Over 24 months, PCGrimAge remained accelerated with no significant differences between treatment arms (P = .89). However, the median pace of aging by the DunedinPACE increased in the placebo arm (0.036, Q1, Q3 [-0.018, 0.10], P = .021) but not in the pitavastatin arm (0.001, Q1, Q3 [-0.031, 0.036], [P = .77]), treatment group difference (P = .049).
Conclusions:
In this pilot study of REPRIEVE, epigenetic age acceleration was demonstrated at trial entry. The biological pace of aging increased over 24 months in the placebo group as compared to the statin group. These preliminary findings suggest pitavastatin may prevent an increase in the pace of biological aging in PWH and support further research into statin therapy as a potential intervention to mitigate accelerated aging.
Clinical Trials Registration:
NCT02344290 (date of initial registration: 22 January 2015).
