Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults

• Published in: Journal of antimicrobial chemotherapy Vol. 77; no. 4; pp. 1125 - 1132
• Main Authors: Rodríguez-Centeno, Javier, Esteban-Cantos, Andrés, Montejano, Rocío, Stella-Ascariz, Natalia, De Miguel, Rosa, Mena-Garay, Beatriz, Saiz-Medrano, Gabriel, Alejos, Belén, Jiménez-González, María, Bernardino, Jose I., Cadiñanos, Julen, Castro-Alvarez, Juan M., Rodés, Berta, Arribas, Jose R.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 31.03.2022
• Subjects: Adult; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes; HIV Infections; Humans; Telomerase - metabolism; Telomere - metabolism; Tenofovir - therapeutic use
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkab492

Abstract Objectives To evaluate whether the negative impact of tenofovir on telomere length (TL) is due to immune reconstitution interference or inhibition of telomerase. Methods One hundred and twenty-eight long-term aviraemic HIV adults treated with tenofovir-containing (n = 79) or tenofovir-sparing regimens (n = 49) were recruited to compare the following: TL in whole blood, PBMCs, CD4+ T cells and CD8+ T cells by quantitative PCR (qPCR); telomerase activity in PBMCs, CD4+ cells and CD8+ T cells using the TRAPeze RT Telomerase Detection Kit; and T cell maturational subset distribution by flow cytometry. Results In an adjusted analysis, participants treated with tenofovir for at least 4 years had shorter TL in CD8+ T cells (P = 0.04) and lower telomerase activity in CD4+ (P = 0.012) and CD8+ T cells (P = 0.023). Tenofovir treatment was also associated with lower proportions of recent thymic emigrant (RTE) CD4+ cells (P = 0.031) and PD1 marker expression (P = 0.013). Conclusions In long-term aviraemic HIV adults, the inhibition of telomerase by tenofovir could explain telomere shortening in CD8+ T cells. There is no telomere shortening in the CD4+ compartment and the decrease in telomerase activity could be explained both by the inhibition by tenofovir and by the lower proportion of RTE CD4+cells.