Association between Combination Antiretroviral Therapy and Telomere Length in People Living with Human Immunodeficiency Virus

Author:

Bukic Ena1ORCID,Milasin Jelena2ORCID,Toljic Bosko2ORCID,Jadzic Jelena3ORCID,Jevtovic Djordje4,Obradovic Bozana1ORCID,Dragovic Gordana1ORCID

Affiliation:

1. Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade Faculty of Medicine, 11000 Belgrade, Serbia

2. Department of Human Genetics, School of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia

3. Center of Bone Biology, University of Belgrade Faculty of Medicine, 11000 Belgrade, Serbia

4. Infective and Tropical Diseases Hospital, University of Belgrade Faculty of Medicine, 11000 Belgrade, Serbia

Abstract

Long-term exposure to combination antiretroviral therapy (cART) may be associated with accelerated ageing. Telomere length is considered to be reliable aging biomarker. The aim of this study was to compare patients’ relative telomere length (RTL) between and within different cART classes and to estimate the impact of certain HIV-related variables on RTL. The study was conducted in 176 HIV-infected male patients receiving cART, with ≤50 copies HIV RNA/mL plasma. RTL was determined from mononuclear cells by quantitative polymerase chain reaction. Standard statistical tests and unsupervised machine learning were performed. The mean RTL was 2.50 ± 1.87. There was no difference (p = 0.761) in RTL between therapeutic groups: two nucleoside reverse transcriptase inhibitors as the backbone treatment, combined with either integrase inhibitor, protease inhibitor, or non-nucleoside reverse transcriptase inhibitor (NNRTI). Machine learning results suggested duration of HIV infection, CD4+ T-cell count, and cART, including NNRTI, as potentially significant variables impacting RTL. Kendall’s correlation test excluded duration of HIV infection (p = 0.220) and CD4+ T-cell count (p = 0.536) as significant. The Mann–Whitney test confirmed that cART containing NNRTI impacted RTL (p = 0.018). This was the first study to show that patients using efavirenz within cART had significantly shorter telomeres than patients using nevirapine.

Funder

the Ministry of Education and Science of the Republic of Serbia

Publisher

MDPI AG

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology

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