December 16, 2005
Although once-daily (QD) antiretroviral regimens have become more common, it has been difficult to prove that adherence on such regimens is better than with regimens that are given twice daily (BID). Furthermore, the association between level of adherence with once-daily or twice-daily regimens and virologic outcome is not clear.
This analysis of a once-daily versus twice-daily lopinavir/ritonavir (LPV/r, Kaletra) study evaluated medication compliance and its relationship to treatment success.
Study M02-418 compared the safety, tolerability, antiviral efficacy and pharmacokinetics of lopinavir/ritonavir soft-gel capsules, administered QD (800/200 mg, 6 capsules QD) or BID (400/100 mg, 3 capsules BID), with 300 mg tenofovir (TDF, Viread) and 200 mg emtricitabine (FTC, Emtriva) (both QD) in antiretroviral-naive, HIV-1-infected patients.
As reported previously, the results of this study showed that QD and BID lopinavir/ritonavir were virologically non-inferior, although the once-daily treatment group had an increased incidence of diarrhea. During the study, compliance was assessed by MEMS caps, which electronically recorded lopinavir/ritonavir bottle openings for trial participants.
Adherence included three measures:
In all three analyses, which were conducted over 96 weeks of follow-up, the once-daily treatment arm showed better adherence than the twice-daily group. For example, in the first of these measures -- the percentage of prescribed doses taken -- 97.2% (baseline to week 4) to 92.8% (weeks 84-96) of the QD group took their prescribed doses, versus 92.2% (baseline to week 4) to 80.8% (weeks 84-96) for the BID group. More marked differences were seen in percentage of days with correct number of doses and percentage of doses taken within timing intervals.
In another study, which is of relevance to those who are starting lopinavir/ritonavir-based therapy with the new tablet formulation, 15 healthy volunteers participated in a crossover study of 800 mg/200 mg lopinavir/ritonavir once-daily soft-gel capsules versus 800 mg/200 mg lopinavir/ritonavir tablets.
The pharmacokinetic analysis of the study showed that concentrations of lopinavir and ritonavir were generally similar or slightly higher using the new tablet formulation, with approximately 17% greater bioavailability for the tablet. Importantly, the tablet formulation demonstrated a lower incidence of adverse effects, in particular diarrhea.
Taken in aggregate, these two studies demonstrate that adherence with a once-daily lopinavir/ritonavir-based regimen is likely to be better than a twice-daily lopinavir/ritonavir-based regimen. Furthermore, the tablet formulation will reduce the main disincentive to converting to QD therapy, namely the higher incidence of diarrhea. Studies of once-daily lopinavir/ritonavir in this new tablet formulation in both treatment-naive and treatment-experienced studies are either currently underway or planned.
Abstract: New tablet formulation of lopinavir/ritonavir is bioequivalent to the capsule at a dose of 800/200 mg (Poster H-1894)
Authored by: T Zhu, Y Chiu, T Doan, C Klein, M Chang, S Brun, G Hanna, W Awni
Affiliations: Abbott Lab., Abbott Park, IL
View poster: Download PDF
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