No difference in the rate of change in telomere length or telomerase activity in HIV-infected patients after three years of darunavir/ritonavir with and without nucleoside analogues in the MONET trial

PLoS One. 2014 Nov 4;9(11):e109718. doi: 10.1371/journal.pone.0109718. eCollection 2014.

Abstract

Objective: To determine whether nucleos(t)ide reverse transcriptase inhibitors (NRTI) contribute to an accelerated loss in telomere length (TL) in HIV-infected patients on antiretroviral therapy (ART).

Design: Substudy of randomised controlled trial.

Methods: Patients with HIV RNA <50 copies/mL on combination ART (n = 256) were randomised to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 127) or with 2 NRTIs (n = 129) for up to 144 weeks. TL and telomerase activity was quantified on stored peripheral blood mononuclear cells (PBMC; n = 124) using quantitative real time PCR.

Results: Patients in the sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4 years (range 1-20 years). As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no significant association between TL and either the duration of prior NRTI treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).

Conclusion: Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Darunavir
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / genetics
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Nucleosides / chemistry*
  • Nucleosides / pharmacology
  • Nucleosides / therapeutic use
  • RNA, Viral / analysis
  • Ritonavir / pharmacology
  • Ritonavir / therapeutic use*
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Telomerase / metabolism*
  • Telomere / drug effects*
  • Telomere / metabolism*

Substances

  • Anti-HIV Agents
  • Nucleosides
  • RNA, Viral
  • Sulfonamides
  • Telomerase
  • Ritonavir
  • Darunavir