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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

2009; Lippincott Williams & Wilkins; Volume: 50; Issue: 5 Linguagem: Inglês

10.1097/qai.0b013e31819c2937

1944-7884

Joseph Gathe, Barbara A. da Silva, Daniel E. Cohen, Mona Loutfy, Daniel Podzamczer, Rafael Rubio, Sara Gibbs, T. David Marsh, Christian Naylor, Linda Fredrick, Barry Bernstein,

HIV/AIDS Research and Interventions

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 0.999) or when analyzed by baseline CD4+ T-cell count (<50, 50 to <200, and ≥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.