Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging

Edwin Leeansyah, Paul Urquhart Cameron, Ajantha Solomon, Gayani Surekha Tennakoon, Pushparaj Velayudham, Maelenn Gouillou, Tim Denis Spelman, Anna Clare Hearps, Christopher Kit Fairley, Devilliers Smit, Anna Pierce, Jude Armishaw, Suzanne Mary Crowe, David A Cooper, Kersten K Koelsch, Jun-Ping Liu, John Chuah, Sharon R Lewin

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Abstract

Human immunodeficiency virus (HIV)-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of telomerase activity.Methods. Telomerase activity and telomere length (TL) were measured by quantitative polymerase chain reaction in vitro in activated peripheral blood mononuclear cells (PBMCs) cultured with NRTI and ex vivo in PBMCs from uninfected patients exposed to NRTI and from HIV-infected patients on NRTI-containing cART.Results. Lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir significantly inhibited telomerase activity in activated PBMCs in vitro. Tenofovir was the most potent inhibitor of telomerase activity and caused greatest shortening of TL in vitro at the therapeutic concentration of 0.3 ?M. PBMCs from HIV-infected patients receiving NRTI-containing cART (n = 39) had significantly lower telomerase activity than HIV-uninfected patients (n = 47; P =. 011) and HIV-infected patients receiving non-NRTI-containing cART (n = 11; P
Original languageEnglish
Pages (from-to)1157 - 1165
Number of pages9
JournalJournal of Infectious Diseases
Volume207
Issue number7
DOIs
Publication statusPublished - 2013

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