title: HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study.
abstract: BACKGROUND
  The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The present report focuses on lamin A processing, a pathway known to be altered in systemic genetic progeroid syndromes.
  
  
  METHODS
  35 HIV-1 infected patients being treated with first line antiretroviral therapy (ART, mean duration at inclusion: 2.7±1.3 years) containing boosted protease inhibitors (PI/r) (comprising lopinavir/ritonavir in 65% of patients) were recruited together with 49 seronegative age- and sex-matched control subjects (http://clinicaltrials.gov/, NCT01038999). In more than 88% of patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm³. Prelamin A processing in peripheral blood mononuclear cells (PBMCs) from patients and controls was analysed by western blotting at inclusion. PBMCs from patients were also investigated at 12 and 24 months after enrolment in the study. PBMCs from healthy controls were also incubated with boosted lopinavir in culture medium containing various concentrations of proteins (4 to 80 g/L).
  
  
  RESULTS
  Lamin A precursor was not observed in cohort patient PBMC regardless of the PI/r used, the dose and the plasma concentration. Prelamin A was detected in PBMC incubated in culture medium containing a low protein concentration (4 g/L) but not in plasma (60-80 g/L) or in medium supplemented with BSA (40 g/L), both of which contain a high protein concentration.
  
  
  CONCLUSIONS
  Prelamin A processing abnormalities were not observed in PBMCs from patients under the PI/r first line regimen. Therefore, PI/r do not appear to contribute to lamin A-related aging in PBMCs. In cultured PBMCs from healthy donors, prelamin A processing abnormalities were only observed when the protein concentration in the culture medium was low, thus increasing the amount of PI available to enter cells. ClinicalTrials.gov NCT01038999 http://clinicaltrials.gov/ct2/show/NCT01038999.
authors.affiliation: Inserm UMR_S 910, Aix-Marseille Université, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Perrin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cremer
authors.forename: Olivia
authors.initials: O
authors.lastname: Faucher
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Pierre
authors.initials: P
authors.lastname: Dellamonica
authors.forename: Joëlle
authors.initials: J
authors.lastname: Micallef
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
authors.forename: Charlotte
authors.initials: C
authors.lastname: Stretti
authors.forename: Elise
authors.initials: E
authors.lastname: Kaspi
authors.forename: Andrée
authors.initials: A
authors.lastname: Robaglia-Schlupp
authors.forename: Corinne
authors.initials: C
authors.lastname: Nicolino-Brunet
authors.forename: Corine Nicolino-Brunet Catherine
authors.initials: CN
authors.lastname: Tamalet
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.forename: Pierre
authors.initials: P
authors.lastname: Cau
authors.forename: Patrice
authors.initials: P
authors.lastname: Roll
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D034904:Lamin Type A; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism* / Q000821:virology; D008137:Longitudinal Studies; D061466:Lopinavir / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D011498:Protein Precursors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D034904:Lamin Type A; D009687:Nuclear Proteins; D009842:Oligopeptides; D011498:Protein Precursors; D011725:Pyridines; D013449:Sulfonamides; C090764:prelamin A; D061466:Lopinavir; D000069446:Atazanavir Sulfate; C095108:amprenavir; D019438:Ritonavir