Another protease inhibitor looks set to move to once daily dosing, according to the findings of 48 week study presented on Wednesday at the Ninth Annual Retroviruses Conference in Seattle. Lopinavir/ritonavir (Kaletra) dosed once daily appears to be just as effective as lopinavir/ritonavir dosed twice daily in treatment-naïve patients.
Thirty eight patients were randomised to receive either 800 mg of lopinavir and 200 mg of ritonavir once daily, or the standard dose of lopinavir/ritonavir (400/100 mg), together with d4T and 3TC.
After 48 weeks, the proportions with viral load below 50 copies was similar in each group: 74% in the once daily group and 79% in the twice daily group by intent to treat analysis. No differences in adverse events or lipid elevations were observed between the two groups, and adherence was similar in each group.
The only notable difference between the two doses was observed when the ratio of the lopinavir trough level to the lopinavir IC50 was calculated. The IC50 is the drug concentration needed to inhibit virus replication by 50% when compared with no drug at all, so the ratio of trough level to IC50 shows the safety margin between the minimum drug level reached during the day and the drug concentration at which a high risk of resistance can be expected. This ratio has been called the Inhibitory Quotient (IQ).
The ratio of trough level to IC50 for once daily lopinavir dosing was 40, with a range of 3.6 to 220 observed in the 19 individuals who received once daily lopinavir. In contrast, the ratio in those who received twice daily dosing was 84, with a range of 36 to 174 observed in the 19 individuals who received twice daily dosing. However, no relationship between IQ and viral load suppression was noted in this study.
Eron J et al. Once-daily vs twice-daily Kaletra (Lopinavir/Ritonavir) in antiretroviral-naïve HIV+ patients: 48-week follow-Up. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 409, 2002.