Background: Kaletra is a coformulation of lopinavir (LPV), an HIV protease inhibitor, and ritonavir (r), which provides enhanced LPV plasma conc. A LPV/r dose of 400/100 mg BID yields a LPV mean inhibitory quotient (IQ), or C trough/protein binding (PB)-corrected wt-HIV IC₅₀, > 75.

Methods: ARV-naïve HIV+ subjects (n=38) were randomized to LPV/r 400/100 mg BID or LPV/r 800/200 mg QD, with d4T and 3TC; LPV/r was taken with food. Plasma conc were measured using LC/MS/MS over a dosing interval at week  3; an additional C trough was obtained on week 8, 16, 24, and 48. Noncompartmental pharmacokinetic (PK) parameters were log-transformed and compared using ANOVA with effects for regimen, gender, and race.

Results: Steady-state (week 3) PK parameters (mean ± SD) are presented below:

LPV/r 800/200 mg qd and 400/100 mg BID produced similar LPV C max (p=0.19) and AUC (p=0.68). LPV C trough did not differ over time from week 3 to 48 (p=0.55). C trough and IQ from week 3-48 were lower and more variable in qd vs BID (p<0.01); median IQ was ³ 40 (LPV conc ³ 2.8 mg/mL) for both regimens. The proportion of subjects with viral load (VL) < 50 copies/mL was similar at WK 48 between qd (74%) and BID (79%) by intent-to-treat analysis. No relationship between IQ and VL response was noted, reflecting in part the relatively high drug conc.

Conclusions: LPV/r 800/200 mg qd produced steady-state LPV C max and AUC similar to 400/100 mg BID. Median trough concentrated over 48 weeks exceeded the PB-adjusted IC₅₀ of wt-HIV by 40- and 84-fold in the qd and BID regimens, respectively; C trough was more variable after qd. The clinical efficacy of qd and BID was similar after 48 weeks in these ARV-naïve subjects.