title: In vitro susceptibility and virological outcome to darunavir and lopinavir are independent of HIV type-1 subtype in treatment-naive patients.
abstract: BACKGROUND
  The effect of HIV type-1 (HIV-1) subtype on in vitro susceptibility and virological response to darunavir (DRV) and lopinavir (LPV) was studied using a broad panel of primary isolates, and in recombinant clinical isolates from treatment-naive, HIV-1-infected patients in the Phase III trial, AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS).
  
  
  METHODS
  Patients received DRV/ritonavir (DRV/r) 800/100 mg once daily (n=343) or LPV/ritonavir (LPV/r) 800/200 mg total daily dose (n=346), plus a fixed daily dose of emtricitabine and tenofovir disoproxil fumarate.
  
  
  RESULTS
  DRV demonstrated high antiviral activity against a broad panel of HIV-1 major group (M) and outlier group (O) primary isolates in peripheral blood mononuclear cells, with a median 50% effective concentration (EC(50)) of 0.52 nM. Most (61%) patients in ARTEMIS harboured HIV-1 subtype B; other prevalent subtypes were C (13%) and CRF01_AE (17%); 9% harboured other subtypes. Median EC(50) values (interquartile range) for DRV were 1.79 nM (1.3-2.6) for subtype B, 1.12 nM (0.8-1.4) for C and 1.27 nM (1.0-1.7) for CRF01_AE. Virological response to DRV/r (HIV-1 RNA<50 copies/ml [intent-to-treat, time-to-loss of virological response algorithm]) was 81%, 87% and 85% for patients with subtype B, C and CRF01_AE infections, respectively. Similar results were observed in the LPV/r treatment group.
  
  
  CONCLUSIONS
  In vitro susceptibility to DRV was comparable across HIV-1 subtypes in a broad panel of primary isolates and in recombinant clinical isolates. Once daily DRV/r 800/100 mg and LPV/r 800/200 mg were highly effective in ARTEMIS irrespective of the HIV-1 subtype studied, confirming their broad anti-HIV-1 activity.
authors.affiliation: Tibotec BVBA, Mechelen, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Dierynck
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Erkki
authors.initials: E
authors.lastname: Lathouwers
authors.forename: Carline
authors.initials: C
authors.lastname: Vanden Abeele
authors.forename: Tom
authors.initials: T
authors.lastname: Van De Casteele
authors.forename: Sabrina
authors.initials: S
authors.lastname: Spinosa-Guzman
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: de Béthune
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
mesh_terms: D000218:Adamantane / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000494:pharmacology; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D061466:Lopinavir; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D019888:Nelfinavir / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D019562:Viral Load
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D011753:Pyrones; D013449:Sulfonamides; D061466:Lopinavir; D000069446:Atazanavir Sulfate; C095108:amprenavir; D019469:Indinavir; D009439:Neuraminidase; D019888:Nelfinavir; D019258:Saquinavir; D000218:Adamantane; D000069454:Darunavir; C107201:tipranavir