Background:  Short-course intrapartum/postpartum ART can reduce the incidence of nevirapine (NVP) resistance in HIV-infected pregnant women who receive a single intrapartum dose; however, the optimal choice and duration of such treatment remains unknown. IMPAACT P1032 is a randomized study of 3 regimens to reduce the incidence of NVP resistance following a single intrapartum 200-mg dose. One arm is a 30-day course of lopinavir/ritonavir (LPV/r, 3 soft gel caps, 400/100 mg twice daily), zidovudine (ZDV, 300 mg twice daily), and didanosine-enteric coated (ddI, 250 mg if body weight <60 kg or 400 mg if >60 kg, once daily), initiated during labor. Previous studies have shown reduced LPV exposure during pregnancy, but there are no data describing LPV pharmacokinetics in the immediate and early postpartum period. Thus, the first 18 women in this arm were scheduled to have LPV pharmacokinetics postpartum assessed to ensure adequate LPV exposure.

Methods:  Within 72 hours after delivery, plasma samples were collected pre-dose and 1, 2, 4, 6, 8, and 12 hours post-dose. Pre-dose, 2- and 4-hour post-dose samples were also collected at 30 days postpartum.  LPV plasma levels were determined by high-performance liquid chromatography (HPLC) and pharmacokinetics parameters by non-compartmental analysis. Target LPV area under the concentration-time curve (AUC) was ≥52 µg·h/mL, the 10th percentile for LPV AUC in nonpregnant adults.

Results:  LPV pharmacokinetic sampling was available in 16 women. Median age (range) was 27 years (18 to 38) and CD4 cell count 464 cells/mm³ (292 to 844). On the day of intensive pharmacokinetic sampling, median weight was 58 kg (44 to 84) and duration of LPV/r intake was 2 days (1 to 4). LPV AUC, C_max and C_min were 99.7 µg·h/mL (66.1 to 180.5), 11.2 µg/mL (8.0 to 17.5) and 4.6 µg/mL (1.7 to 12.5), respectively.  All women had an LPV AUC above the target threshold. At 30 days postpartum, median LPV levels were 9.17 µg/mL (5.3 to 15.0) pre-dose and 13.0 µg/mL (8.8 to 21.3) 4 hours post-dose, significantly higher compared to 6.08 µg/mL (2.3 to 13.6) (p = 0.01) and 10.8 µg/mL (8.0 to 16.8) (p = 0.05) within 72 hours postpartum, respectively. No unexpected serious adverse events were reported in these women.

Conclusions:  Although standard dosing during the third trimester of pregnancy is not sufficient in U.S. women, Thai women initiating standard LPV/r dosing during labor achieved LPV exposure at 72 hours and 30 days postpartum similar to that seen in nonpregnant adults in the United States.