Forty women (87%) had LPV concentrations above the accepted
minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823–4227) ng/mL; n=16] and third [3346 (2813–3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693–6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851–4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the check details LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases. Highly active antiretroviral therapy (HAART) is recommended during pregnancy for the benefit of maternal health and
to decrease the risk of vertical transmission [mother-to-child transmission (MTCT)] of HIV-1 virus to the baby. For treatment of HIV-infected pregnant women, the current British HIV Association (BHIVA) guidelines recommend a ritonavir (RTV)-boosted protease inhibitor (PI) in combination with a dual nucleoside reverse transcriptase find more inhibitor
(NRTI) backbone, preferably containing zidovudine and lamivudine [1]. Lopinavir/ritonavir (LPV/r) is used in pregnancy as it is potent and well tolerated and has no obvious human teratogenic effects [2]. A number of studies report reduced LPV exposure during the later stages of pregnancy (third trimester) in patients receiving standard dosing of the LPV/r soft gel capsule (SGC; 400/100 mg twice daily) [3–6]. Subsequently more favourable LPV concentrations were demonstrated when the SGC dose was increased to 533/133 mg twice daily [7]. In June 2006, the SGC Rucaparib mw formulation was phased out of clinical practice and replaced by a new LPV/r tablet formulation. To date, pharmacokinetic data on the LPV/r tablet in pregnancy are limited to a few conflicting small cohort studies. Data from a therapeutic drug monitoring (TDM) cohort of 25 patients showed LPV concentrations to be subtherapeutic in ∼20% of women during pregnancy [8] whereas others have reported no pregnancy-associated changes in LPV/r tablet pharmacokinetics [9–10]. Comprehensive pharmacokinetic studies on the LPV/r tablet are important as there are currently insufficient data to allow robust recommendations to be made regarding dosing in pregnancy.