Lopinavir exposure with an increased dose during pregnancy

Abstract

Background: Use of standard adult lopinavir/ritonavir (LPV/RTV) dosing (400/100 mg) during the third trimester of pregnancy results in reduced LPV exposure. The goal of this study was to determine LPV exposure during the third trimester of pregnancy and 2 weeks postpartum with a higher LPV/RTV dose.

Methods: The Pediatric AIDS Clinical Trials Group Protocol 1026s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving LPV/RTV 400/100 mg twice daily during the second trimester and 533/133 mg twice daily during the third trimester through 2 weeks postpartum. Intensive steady state 12-hour pharmacokinetic profiles were performed during the third trimester and at 2 weeks postpartum and were optional during the second trimester. LPV and RTV were measured by reverse-phase high-performance liquid chromatography with a detection limit of 0.09 microg/mL.

Results: Twenty-six HIV-infected pregnant women were studied. Median LPV area under the plasma concentration-time curve (AUCs) for the second trimester, third trimester, and postpartum were 57, 88, and 152 microg.h.mL, respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 microg/mL.

Conclusions: The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 microg.h.mL) in nonpregnant adults taking standard doses. However, the AUC on this increased dose at 2 weeks postpartum was considerably higher. These data suggest that the higher LPV/RTV dose should be used in third trimester pregnant women; that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced; and that postpartum LPV/RTV dosing can be reduced to standard dosing by 2 weeks after delivery.

FIGURE 1

Median LPV concentrations during second trimester, third trimester, and postpartum. Median LPV concentration-time curves ± SE during the second trimester (solid line, n = 8), third trimester (coarse dashed line, n = 26), and postpartum (fine dashed line, n = 22).

FIGURE 2

LPV plasma concentrations during pregnancy and two weeks postpartum. Solid lines represent individual LPV profiles during the second trimester (A, n = 17), third trimester (B, n = 26), and postpartum (C, n = 23). The broken lines represent the typical (50th percentile) concentrations in nonpregnant historical subjects.

FIGURE 3

LPV AUC second trimester, third trimester, and two weeks postpartum. Changes in LPV AUC from the second trimester to the third trimester to postpartum (n = 24). The solid line indicates typical value (50th percentile) AUC in nonpregnant adults of 83 µg·h⁻¹·mL⁻¹.