title: A once-daily lopinavir/ritonavir-based regimen is noninferior to twice-daily dosing and results in similar safety and tolerability in antiretroviral-naive subjects through 48 weeks.
abstract: BACKGROUND
  Lopinavir/ritonavir (LPV/r)-dosed twice daily has demonstrated durable efficacy in antiretroviral-naive and protease inhibitor (PI) -experienced patients. Study M05-730 compared LPV/r tablets dosed once daily vs. twice daily in antiretroviral-naive subjects.
  
  
  METHODS
  Six hundred sixty-four subjects were randomized to LPV/r soft gel capsules (SGCs) once daily, SGC twice daily, tablets once daily, and tablets twice daily, all with tenofovir and emtricitabine once daily. At week 8, all SGC-treated subjects were switched to tablets, maintaining randomized dose frequency. The primary efficacy analysis used an intent-to-treat, noncompleter = failure approach to assess noninferiority of the LPV/r once-daily group compared with the twice-daily group.
  
  
  RESULTS
  At week 48, 77% of once-daily-dosed subjects vs. 76% of twice-daily-dosed subjects had HIV-1 RNA <50 copies per milliliter (P = 0.715; 95% confidence interval for difference: 5% to 8%). Response rates were numerically similar between the once-daily and twice-daily groups among subjects with baseline HIV-1 RNA > or = 100,000 copies per milliliter (75% once daily vs. 74.6% twice daily; P > 0.999) or when analyzed by baseline CD4+ T-cell count (<50, 50 to <200, and > or = 200 cells/mm3). Rates of discontinuation and adverse events, including diarrhea, were similar between arms. Among subjects with protocol-defined virologic rebound through week 48, no new PI resistance mutations were detected.
  
  
  CONCLUSIONS
  At 48 weeks, the antiviral response in the LPV/r once-daily group was noninferior to the twice-daily group when coadministered with tenofovir and emtricitabine in antiretroviral-naive subjects. Efficacy was comparable between the once-daily and twice-daily groups regardless of baseline HIV-1 RNA or CD4+ T-cell count. Safety and tolerability of once-daily and twice-daily dosing was also comparable. No new PI resistance mutations were detected upon virologic rebound.
authors.affiliation: Therapeutic Concepts, Houston, TX, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gathe
authors.forename: Barbara A
authors.initials: BA
authors.lastname: da Silva
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Cohen
authors.forename: Mona R
authors.initials: MR
authors.lastname: Loutfy
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Rafael
authors.initials: R
authors.lastname: Rubio
authors.forename: Sara
authors.initials: S
authors.lastname: Gibbs
authors.forename: Theresa
authors.initials: T
authors.lastname: Marsh
authors.forename: Christian
authors.initials: C
authors.lastname: Naylor
authors.forename: Linda
authors.initials: L
authors.lastname: Fredrick
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D002214:Capsules; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013607:Tablets
chemical_list: D002214:Capsules; D011744:Pyrimidinones; D013607:Tablets; D061466:Lopinavir; D019438:Ritonavir