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

Authors:
  • BSBarbara A da Silva
    Barbara A da Silva
  • DCDaniel E Cohen
    Daniel E Cohen
  • MLMona R Loutfy
    Mona R Loutfy
  • DPDaniel Podzamczer
    Daniel Podzamczer
  • RRRafael Rubio
    Rafael Rubio
  • SGSara Gibbs
    Sara Gibbs
  • TMTheresa Marsh
    Theresa Marsh
  • CNChristian Naylor
    Christian Naylor
  • LFLinda Fredrick
    Linda Fredrick
  • BBBarry Bernstein
    Barry Bernstein
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Abstract
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. 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. At week 48, 77% of once-daily-dosed subjects vs. 76% of twice-daily-dosed subjects had 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 ( 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. 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.
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