Lopinavir exposure with an increased dose during pregnancy

Area of Science:

• Pharmacokinetics
• HIV/AIDS Treatment
• Maternal-Fetal Health

Background:

• Standard lopinavir/ritonavir (LPV/RTV) adult dosing results in lower drug exposure during the third trimester of pregnancy.
• Understanding drug pharmacokinetics in pregnant populations is crucial for effective HIV management.

Purpose of the Study:

• To assess lopinavir (LPV) exposure in pregnant women during the third trimester and postpartum using an escalated LPV/RTV dose.
• To inform optimal antiretroviral dosing strategies during and after pregnancy.

Main Methods:

• Prospective pharmacokinetic study (Pediatric AIDS Clinical Trials Group Protocol 1026s) in 26 HIV-infected pregnant women.
• Administered escalated LPV/RTV (533/133 mg twice daily) in the third trimester and postpartum.
• Measured LPV and RTV plasma concentrations using high-performance liquid chromatography.

Main Results:

• Median LPV area under the curve (AUC) was 88 microg.h/mL in the third trimester and 152 microg.h/mL postpartum.
• Median minimum LPV concentrations were 4.1 microg/mL (third trimester) and 8.3 microg/mL (postpartum).
• Third-trimester AUC approximated levels seen in nonpregnant adults on standard doses.

Conclusions:

• The escalated LPV/RTV dose (533/133 mg) is recommended for third-trimester pregnant women to achieve therapeutic LPV exposure.
• Consideration of the escalated dose in the second trimester, particularly for protease inhibitor-experienced patients, is warranted.
• Standard LPV/RTV dosing can be resumed by two weeks postpartum.