Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults. (19th January 2022)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 77:Number 4(2022)
• Page Start: 1125
• Page End: 1132
• Publication Date: 2022-01-19
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkab492
• Languages: English
• ISSNs: 0305-7453

Abstract

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.