Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 77(2022), 4 vom: 31. März, Seite 1125-1132 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rodríguez-Centeno, Javier [VerfasserIn] |
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| Links: |
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| Themen: |
99YXE507IL |
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| Anmerkungen: |
Date Completed 01.04.2022 Date Revised 02.06.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkab492 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM335798594 |
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| 100 | 1 | |a Rodríguez-Centeno, Javier |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 02.06.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a OBJECTIVES: To evaluate whether the negative impact of tenofovir on telomere length (TL) is due to immune reconstitution interference or inhibition of telomerase | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a 99YXE507IL |2 NLM | |
| 650 | 7 | |a Telomerase |2 NLM | |
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| 700 | 1 | |a Esteban-Cantos, Andrés |e verfasserin |4 aut | |
| 700 | 1 | |a Montejano, Rocío |e verfasserin |4 aut | |
| 700 | 1 | |a Stella-Ascariz, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a De Miguel, Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Mena-Garay, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Saiz-Medrano, Gabriel |e verfasserin |4 aut | |
| 700 | 1 | |a Alejos, Belén |e verfasserin |4 aut | |
| 700 | 1 | |a Jiménez-González, María |e verfasserin |4 aut | |
| 700 | 1 | |a Bernardino, Jose I |e verfasserin |4 aut | |
| 700 | 1 | |a Cadiñanos, Julen |e verfasserin |4 aut | |
| 700 | 1 | |a Castro-Alvarez, Juan M |e verfasserin |4 aut | |
| 700 | 1 | |a Rodés, Berta |e verfasserin |4 aut | |
| 700 | 1 | |a Arribas, Jose R |e verfasserin |4 aut | |
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