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Background: In a pilot study, the safety, tolerability, and antiviral activity of a once-daily lopinavir/ritonavir (LPV/r)-based regimen appeared comparable to that of a twice-daily LPV/r-based regimen.

Methods:  Study 418, the first trial of an entirely once-daily LPV/r-based regimen, is a prospective, randomized, open-label clinical trial of LPV/r 800/200 mg once daily (n = 115) vs LPV/r 400/100 mg twice daily (n = 75), each dosed with once-daily emtricitabine (FTC) and tenofovir DF (TDF) in antiretroviral-naive patients.

Results:  Median baseline viral load and CD4 count were 4.8 log₁₀ copies/mL and 216 cells/mm³, respectively. Prior to week 48, 17% (once daily) and 20% (twice daily) patients discontinued, primarily due to adverse events (11% once daily, 5% twice daily) or loss to follow-up or non-adherence (2% once daily, 11% twice daily). Virologic responses through 40 to 48 weeks were comparable between arms (see the table below). The 95% CI for the difference in week 40 intent-to-treat NC = F response proportion (once daily minus twice daily) was (-8%, 20%). Genotypic resistance testing was conducted on all samples with HIV RNA >500 copies/mL from week 12 to 24. Results from 14 patients (8 once daily, 6 twice daily) indicated no new primary or active site protease inhibitor mutations. No patient demonstrated tenofovir resistance (K65R mutation in reverse transcriptase) and 3 patients (2 once daily, 1 twice daily) demonstrated FTC resistance (M184V/I mutation). Mean increases in CD4 count from baseline to week 40 were 162 (once daily) and 166 (twice daily) cells/mm³. 

Adverse event and laboratory data to date:  diarrhea (13% once daily, 5% twice daily, p = 0.14) and nausea (10% once daily, 8% twice daily) were the most common moderate or severe, study drug-related adverse effects, and 79% and 77% of patients had maximum total cholesterol or triglycerides values of grade 0 to 1 (<240 mg/dL and <400 mg/dL, respectively). Preliminary week 48 data indicate no significant changes from baseline in LDL:HDL or Total:HDL cholesterol ratios. Complete week 48 efficacy, safety, and resistance data will be presented.

Conclusions:  Through 40 to 48 weeks, a once daily regimen of TDF+FTC+LPV/r resulted in similar virologic responses in antiretroviral-naive patients compared to the same regimen with LPV/r dosed twice daily. Both regimens were well tolerated, and no protease inhibitor or tenofovir resistance has been observed to date.

Keywords: Lopinavir/ritonavir; Once Daily vs Twice Daily; Week 48