Elvitegravir (EVG), an integrase strand transfer inhibitor, is significantly metabolized by CYP3A and UGT 1A1/3, and must be administered with a pharmacokinetic (PK) booster. It has not been studied in pregnant women or infants. This study described EVG/cobicistat (COBI) exposure during pregnancy compared to postpartum and in infant washout samples after delivery.
IMPAACT protocol P1026s is an ongoing, nonrandomized, open-label, parallel-group, multi-center, international and domestic, phase-IV prospective study of antiretroviral PK in HIV-infected pregnant women. Intensive steady-state 24 hour PK profiles of EVG/COBI following 150/150 mg once-daily dosing were performed during the 2nd trimester (2T), 3rd trimester (3T) and 6-12 weeks postpartum (PP). Infant EVG washout samples were collected if birth weight > 1000 grams and there were no severe malformations or medical conditions. EVG/COBI were measured by validated LC-MS/MS with a quantitation limit of 10 ng/mL. A two-tailed Wilcoxon signed rank test (α = 0.10) was employed for paired within-subject comparison.
Twenty-nine subjects from the US were enrolled – 19 black, 3 white, 6 Hispanic, 1 Asian/Pacific Islander with a median age of 29 years at 3T (range 19 – 48). EVG/COBI PK data were available for 16, 20 and 15 women in 2T, 3T and PP, respectively. EVG exposure was lower and clearance was higher in the 2T and 3T compared to PP (Table 1). COBI exposure was lower and clearance higher in the 2T and 3T compared to postpartum, significantly for 3T. Washout EVG/COBI PK data were available for 18 infants; EVG elimination half-life was 7.4 hours (range 4.3 – 13); COBI was undetectable in all infant samples. Viral load at delivery was < 50 copies/mL for 14 of 19 women (74%). Median infant gestational age at birth was 38.8 weeks. Congenital anomalies were reported in 2 infants. Twenty of 26 infants were HIV-negative based on best available data, and 6 are indeterminate or pending thus far.
EVG/COBI exposure are substantially lower in pregnancy compared to postpartum. Infant EVG elimination half-life was similar to postpartum maternal subjects and historical non-pregnant adult controls. More PK, safety and outcome data in pregnant women are needed before EVG/COBI can be recommended for use during pregnancy.