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This work was supported by ViiV Healthcare. A.E.-C. is supported by a PFIS fellowship from Instituto de Salud Carlos III-Fondo Social Europeo (FI17/00194). R.DM and J.C. are supported by a Rio Hortega fellowship from Instituto de Salud Carlos III-Fondo Social Europeo (CM17/00064 and CM19/00059).

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

Publicado en:JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 77 (4): 1125-1132 - 2022-03-31 77(4), DOI: 10.1093/jac/dkab492

Autores: Rodriguez-Centeno, Javier; Esteban-Cantos, Andres; Montejano, Rocio; Stella-Ascariz, Natalia; De Miguel, Rosa; Mena-Garay, Beatriz; Saiz-Medrano, Gabriel; Alejos, Belen; Jimenez-Gonzalez, Maria; Bernardino, Jose, I; Cadinanos, Julen; Castro-Alvarez, Juan M.; Rodes, Berta; Arribas, Jose R.;

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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.

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