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

J Infect Dis. 2018 Oct 5;218(10):1531-1540. doi: 10.1093/infdis/jiy364.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dideoxynucleosides / pharmacology
  • Dideoxynucleosides / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / genetics
  • HIV Infections* / virology
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors* / pharmacology
  • Reverse Transcriptase Inhibitors* / therapeutic use
  • Telomerase
  • Telomere / drug effects*
  • Tenofovir / pharmacology
  • Tenofovir / therapeutic use
  • Viral Load

Substances

  • Dideoxynucleosides
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • Telomerase
  • abacavir