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Impact of Nucleos(t)ide Reverse Transcriptase Inhibitors on Blood Telomere Length Changes in a Prospective Cohort of Aviremic HIV–Infected Adults

2018; Oxford University Press; Volume: 218; Issue: 10 Linguagem: Inglês

10.1093/infdis/jiy364

1537-6613

Rocío Montejano, Natalia Stella-Ascariz, Susana Monge, José Ignacio Bernardino, Ignacio Valero, Marisa Montes, Eulalia Valencia, Luz Martín‐Carbonero, V. Moreno, Juan González‐García, Javier Rodríguez-Centeno, Berta Rodés, Andrés Esteban-Cantos, Belén Alejos, Rosa de Miguel Buckley, Francisco Arnalich, Rosario Perona, José Ramón Arribas,

Telomeres, Telomerase, and Senescence

Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. A prospective cohort of human immunodeficiency virus (HIV)–infected participants with suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF. A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides [of whom 69 were receiving abacavir], 25 were receiving a nucleos[t]ide reverse transcriptase inhibitor [N{t}RTI]–sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside. In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.