3.3 Predictions of LAI CAB and LAI RPV in pregnancy
The predicted PK parameters for the monthly and bimonthly dosing regimens of LAI CAB and LAI RPV in pregnant populations are shown in Figure 2. For both dosing regimens of LAI, the Ctroughof CAB at the end of 12 weeks were predicted to be higher than 4*PAIC90 (0 .664 μg/ml) throughout pregnancy. Likewise, the Ctrough of RPV at the end of 12 weeks were predicted to be higher than 50 ng/ml (standard RPV Ctrough target) [19]. However, the Ctrough of RPV at the end of 12 weeks were predicted to be lower than 70 ng/ml in 3.3, 5.8, 5.5 and 1.8% of the pregnant populations in first, second and third trimester and the non-pregnant adult female population respectively (Table S1).
Unlike the LAI RPV monthly dosing, the Ctrough for the bimonthly dosing of LAI RPV was lower than 50 ng/ml (~4*PAEC90 = 48 ng/ml) in 1, 0.5, 2.3 and 0.8% and lower than 70 ng/ml (newly recommended Ctrough target) in 81.5, 89.3, 81 and 33.3% of the pregnant populations in first, second and third trimester and the non-pregnant adult female population respectively (Table S1). However, Ctrough was above the protein-adjusted EC90 for RPV (12 ng/ml) throughout pregnancy for both the monthly and bimonthly dosing regimen of RPV.