TERT single nucleotide polymorphism rs2736098 but not rs2736100 is associated with telomere length in HIV-infected patients on cART.

BACKGROUND: Continuous application of "combination antiretroviral therapy" (cART) has transformed Human immunodeficiency virus (HIV) infection into a manageable chronic disease; however, due to lasting inflammation and cumulative toxicity, progressive pathophysiological changes do occur and potentially lead to accelerated aging, among others, contributing to telomere shortening. The single nucleotide polymorphisms (SNP) rs2736100 and rs2736098 are particularly important for human telomerase (TERT) gene expression. The objective of this study was to evaluate the effects of clinical parameters and single nucleotide polymorphisms in TERT (rs2736100 and rs2736098) on telomere length in HIV-infected patients. METHODS AND RESULTS: This cross-sectional study included 176 patients diagnosed with HIV infection. Relative telomere length (RTL) was determined by real-time polymerase chain reaction (qPCR), whereas genotyping was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis (PCR-RFLP). The mean age of the patients (p = .904), time since HIV diagnosis (p = .220), therapy-related variables such as the cART regimen (0.761), and total cART duration (p = .096) did not significantly affect RTL. TERT rs2736100 genotype showed no association with RTL. However, TERT rs2736098 heterozygotes (GA) had significantly longer telomeres (P = .049) than both homozygotes (GG and AA). CONCLUSIONS: Our findings support the fact that cellular aging in HIV-infected patients is influenced by the TERT rs2736098 polymorphism.

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

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.

Expression of CYP2B6 Enzyme in Human Liver Tissue of HIV and HCV Patients.

Background and Objectives: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections present significant public health challenges worldwide. The management of these infections is complicated by the need for antiviral and antiretroviral therapies, which are influenced by drug metabolism mediated by metabolic enzymes and transporters. This study focuses on the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in patients with HIV, HCV, and HIV/HCV co-infection, aiming to assess their potential association with the choice of therapy, patohistological and clinical parameters of liver damage such as the stage of liver fibrosis, serum levels of ALT and AST, as well as the grade of liver inflammation and other available biochemical parameters. Materials and Methods: The study included 54 patients who underwent liver biopsy, divided into HIV-infected, HCV-infected, and co-infected groups. The mRNA levels of CYP2B6, CYP3A4, and ABCB1 was quantified and compared between the groups, along with the analysis of liver fibrosis and inflammation levels. Results: The results indicated a significant increase in CYP2B6 mRNA levels in co-infected patients, a significant association with the presence of HIV infection with an increase in CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression was observed in patients using lamivudine. Conclusions: This study provides insight into gene expression of CYP2B6 CYP3A4, and ABCB1 in HIV, HCV, and HIV/HCV co-infected patients. The absence of correlation with liver damage, inflammation, and specific treatment interventions emphasises the need for additional research to elucidate the complex interplay between gene expression, viral co-infection, liver pathology, and therapeutic responses in these particular patients population.