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

Javier Rodríguez-Centeno, Andrés Esteban-Cantos, Rocío Montejano, Natalia Stella-Ascariz, Rosa De Miguel, Beatriz Mena-Garay, Gabriel Saiz-Medrano, Belén Alejos, María Jiménez-González, Jose I. Bernardino, Julen Cadiñanos, Juan M. Castro-Alvarez, Berta Rodés, Jose R. Arribas

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)1125-1132
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume77
Issue number4
DOIs
StatePublished - 1 Apr 2022
Externally publishedYes

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