Lopinavir Exposure With an Increased Dose During Pregnancy

Background: Use of standard adult lopinavir/ritonavir (LPV/RTV) closing (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 all 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 mu g/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 respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 mu g/mL. Conclusions: The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 mu g.h(-1).mL(-1)) 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 closing by 2 weeks after delivery.