title: 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.
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).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.
authors.affiliation: Department of Infectious Diseases, Monash University and Alfred Health, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors.forename: Ajantha
authors.initials: A
authors.lastname: Solomon
authors.affiliation: Department of Infectious Diseases, Monash University and Alfred Health, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors.forename: Surekha
authors.initials: S
authors.lastname: Tennakoon
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Edwin
authors.initials: E
authors.lastname: Leeansyah
authors.affiliation: Hospital la Paz, IdiPAZ, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Arribas
authors.affiliation: Janssen, High Wycombe, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.affiliation: Janssen, Tilburg, Netherlands.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Van Delft
authors.affiliation: Janssen, Neuss, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Moecklinghoff
authors.affiliation: Department of Infectious Diseases, Monash University and Alfred Health, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069454:Darunavir; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D012367:RNA, Viral; D013449:Sulfonamides; D019098:Telomerase; D019438:Ritonavir; D000069454:Darunavir