AEGiS-13CROI [710]: Adequate Lopinavir Exposure Achieved with a Higher Dose during the Third Trimester of Pregnancy

13th Conference on Retroviruses and Opportunistic Infections

Denver, Colorado - February 5-8, 2006

ADEQUATE LOPINAVIR EXPOSURE ACHIEVED WITH A HIGHER DOSE DURING THE THIRD TRIMESTER OF PREGNANCY

Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 710

Mark Mirochnick¹, A Stek², E Capparelli³, B Best³, D Holland³, J Connor³, S Burchett⁴, C Hu⁵, E Smith⁶, J Read⁷, and PACTG 1026s Protocol Team
¹Boston Univ Sch of Publ Hlth, MA, US; ²David Geffen Sch of Med, Univ of California, Los Angeles Med Ctr, US; ³Univ of California, San Diego, US; ⁴Children’s Hosp, Boston, MA, US; ⁵Harvard Sch of Publ Hlth, Boston, MA, US; ⁶NIAID, NIH, DHHS, Bethesda, MD, US; and ⁷Natl Inst Child Hlth and Devt, NIH, DHHS, Bethesda, MD, US

BACKGROUND: Use of standard adult lopinavir/ritonavir (LPV/r) dosing (400 mg/100 mg) during the third trimester of pregnancy results in reduced LPV exposure. Optimal ART exposure during pregnancy is critical for prevention of HIV mother to child transmission (MTCT) and for maternal health. The goal of this analysis was to determine LPV exposure during the third trimester of pregnancy and 2 weeks postpartum with a higher LPV/r dose.

METHODS: PACTG 1026s is an ongoing, prospective, non-blinded study of ART pharmacokinetics in HIV-infected pregnant women that includes a cohort receiving LPV/r 400 mg/100 mg twice daily during the second trimester, and 533 mg/133 mg twice daily during the third trimester through 2 weeks postpartum. Intensive steady-state 12-hour pharmacokinetic profiles were performed during the third trimester and at 2 weeks postpartum, and were optional during the second trimester. Maternal and umbilical cord blood samples were obtained at delivery. LPV was measured by reverse-phase high-performance liquid chromatography (HPLC) with a detection limit of 0.05 µg/mL. Target LPV AUC was > estimated 10^th percentile LPV AUC (>52µg*hr/mL) in non-pregnant historical controls taking the standard dose (mean AUC=80µg*hr/mL).

RESULTS: As of September 2005, LPV pharmacokinetic data were available for 23 women (7 black, 10 Hispanic, 5 white, 1 other; median age 31.9 years, median delivery weight, 79.1 kg). AUC and C_min were significantly lower in third trimester compared with postpartum (p <0.005). Mean cord blood LPV concentration was 1.1±0.7 µg/mL and the mean ratio of cord blood/maternal delivery LPV concentration was 0.24±0.12 (n = 15).

	2nd Trimester	3rd Trimester	2 Weeks Postpartum
LPV/r dose (mg)	400/100 twice daily	533/133 twice daily	533/133 twice daily
Mean AUC ±SD (µg*h/mL)	57.9 ± 21.6	85 ± 28.2	145.8 ± 50.0
Met AUC target/Total	5/8	20/23	17/18
Mean C_min ± SD (µg/mL)	2.4 ± 1.6	4.5 ± 2.4	8.7 ± 4.5

CONCLUSIONS: The higher LPV/r dose (533 mg/133 mg) provided adequate LPV exposure during the third trimester, but resulted in excessive AUC at 2 weeks postpartum. LPV AUC was low with standard dosing (400 mg/100 mg) during the second trimester. These data suggest that the higher LPV/r dose should be used in third trimester pregnant women, that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced, and that postpartum LPV/r dosing can be reduced to standard dosing by 2 weeks after delivery.

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2006-02-05
710

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