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

SIMPLE SUMMARY: Inevitable aging is accompanied by progressive decline in vital functions. People living with HIV infection may experience accelerated aging caused by constant state of inflammation and long-term use of medications that keep HIV infection under control. Human chromosomes end with telomeres—structures that shorten at a steady rate during life. Various harmful influences can contribute to telomere shortening. When telomere length reaches its minimum, the cell dies. If large numbers of cells die, the organism will age rapidly. By monitoring the length of telomeres, it is possible to estimate whether any harmful effect leads to premature aging, decline in the body’s vital functions, and the occurrence of diseases associated with aging. The goal of our study was to identify which medication, used to treat HIV infection, together with changes in the organism, caused by HIV infection, could lead to eventual changes in telomere length. The results of this research could potentially indicate the need to avoid the prescription of efavirenz, which in our study was associated with shorter telomeres, so shortening can be prevented in patients who have never used efavirenz or stopped in patients who already use it. 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.