Impact of nucleos(t)ide reverse transcriptase inhibitors on blood telomere length changes in a prospective cohort of aviremic HIV-infected adults

[Background]: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown.[Methods]: 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.[Results]: 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.[Discussion]: 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.This work was supported by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (grants PI13/01467 and PI14/01495 [supported by the European Regional Development Fund], Rio Hortega fellowship [to R. d. M.], and predoctoral fellowship [to N. S.-A.]).Peer reviewe