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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
HIV Infection as an Independent Factor Accelerating Epigenetic Ageing in Men Treated with Integrase Inhibitors: A
Mateusz Bożejko1, Małgorzata Małodobra-Mazur2, Andrzej Gnatowski3
1Department of Infectious Diseases, Liver Disease and Acquired Immune Deficiencies, Wroclaw Medical University, Koszarowa 5, 51-149 Wroclaw, Poland.
HIV infection accelerates epigenetic ageing, causing DNA hypomethylation and increased DNMT1 gene expression even with successful integrase inhibitor-based treatment. This highlights a persistent aging factor in treated individuals.
Area of Science:
- Epigenetics
- Virology
- Gerontology
Background:
- Published studies indicate HIV infection accelerates epigenetic aging.
- Epigenetic alterations, including DNA methylation changes, are implicated in aging processes.
- Integrase inhibitor (INSTI)-based combined antiretroviral therapy (cART) is a standard treatment for HIV.
Purpose of the Study:
- To determine if HIV infection independently causes DNA hypomethylation and accelerates epigenetic aging in men on INSTI-based cART.
- To investigate the association between HIV infection, DNA methylation patterns, and methyltransferase gene expression.
- To differentiate the effects of HIV from lifestyle factors on epigenetic aging.
Main Methods:
- Comparative study of 48 men living with HIV on INSTI-based cART and 50 uninfected controls.
- Analysis of global and site-specific DNA methylation levels.
- Examination of methyltransferase gene expression (DNMT1, DNMT3a, DNMT3b).
- Inclusion of lifestyle factor questionnaires and basic laboratory blood tests.
- Application of statistical and machine learning methods for data analysis.
Main Results:
- HIV infection showed a strong association with global DNA hypomethylation.
- Higher expression of the methyltransferase gene DNMT1 was significantly associated with HIV infection.
- No association was found with DNA methylation levels of specific genes (CNOT2, DPP6, FOXG1, NPTX2) or expression of DNMT3a and DNMT3b.
- Lifestyle factors were considered and controlled for in the analysis.
Conclusions:
- HIV infection is an independent factor accelerating epigenetic aging in men on successful INSTI-based cART.
- Global DNA hypomethylation and increased DNMT1 expression are key epigenetic alterations linked to HIV in this cohort.
- The findings underscore the long-term epigenetic impact of HIV despite effective treatment.
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