BACKGROUND:: This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum. METHODS:: Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg. RESULTS:: Twenty-four women were included in the analysis. Darunavir AUC0–12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44–0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55–0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24–2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17–2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0–12 was lower during the third trimester [GMR 0.65 (IQR 0.52–0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22–1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted. CONCLUSIONS:: Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.