AEGiS-15IAC: [LbOrB08] REDUCED LOPINAVIR EXPOSURE DURING PREGNANCY: PRELIMINARY PHARMACOKINETIC RESULTS FROM PACTG 1026

15th International AIDS Conference

Bangkok, Thailand — July 11-July 16, 2004

[LbOrB08] REDUCED LOPINAVIR EXPOSURE DURING PREGNANCY: PRELIMINARY PHARMACOKINETIC RESULTS FROM PACTG 1026

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrB08

A Stek¹, M Mirochnick², E Capparelli³, B Best³, S K Burchett⁴, C Hu⁵, J Gardella⁶, C Elgie⁷, J Schiffhauer⁷, E Smith⁸, J Read⁹, R Tuomala¹⁰
¹University of Southern California School of Medicine , Los Angeles, United States; ²Boston University, Boston, United States; ³University of California San Diego, San Diego, United States; ⁴Children's Hospital Boston, Boston, United States; ⁵Harvard School of Public Health, Boston, United States; ⁶PACTG, Silver Spring, United States; ⁷Frontier Science and Technology Research Foundation, Amherst, United States; ⁸NIAID, Bethesda, United States; ⁹NICHD, Bethesda, United States; ¹⁰Brigham and Women's Hospital, Boston, United States

BACKGROUND: Optimal antiretroviral (ARV) exposure during pregnancy is critical for prevention of MTCT and for maternal health. Pregnancy can alter the pharmacokinetics (PK) of ARVs. The objective of this analysis is to describe lopinavir/ritonavir (LPV/r) PK during pregnancy.

METHODS: PACTG 1026s is an on-going, prospective, non-blinded study of ARV PK in HIV-infected women that includes a cohort receiving LPV/r 400/100mg twice daily. Intensive steady-state 12-hour PK profiles were obtained antepartum at 30-36 weeks gestation and postpartum at 6-12 weeks. Maternal and umbilical cord blood PK samples were obtained at delivery. LPV was measured by reverse-phase HPLC with a detection limit of 0.05 mcg/mL. Target LPV AUC was >10th percentile LPV AUC (>52mcg*hr/mL) in non-pregnant historical controls (mean 80mcg*hr/mL).

RESULTS: As of April 2004, 12 women completed antepartum PK evaluations (6 black, 4 Hispanic, 1 Asian, 1 white). Median age was 30 yrs, weight 82 kg. Average antepartum LPV AUC was 44 ± 17 mcg*hr/mL (95% CI 34-54) and trough concentration (Cmin) was 2.0 ± 0.9 mcg/mL (95% CI 1.4-2.5). Four women completed postpartum PK evaluations; average LPV AUC was 77 ± 21 mcg*hr/mL (95% CI 56-98) and Cmin was 4.2 ± 1.5 mcg/mL (95% CI 2.7-5.7). The average ratio of antepartum/postpartum LPV AUC was 0.67±0.19 (95%CI 0.50-0.84). Ten of 12 pregnant and 1of 4 postpartum women did not meet our target LPV AUC. In the 5 sets of maternal and cord blood samples obtained, cord blood LPV concentration averaged 0.55 ± 0.24 mcg/mL and the ratio of cord blood/maternal LPV concentration averaged 0.23 ± 0.18.

CONCLUSIONS: LPV exposure during the third trimester of pregnancy is lower compared to postpartum and non-pregnant historical controls. Small amounts of LPV cross the placenta. Low level exposure to LPV during pregnancy could lead to inadequate viral suppression and viral resistance. The PK, safety, and efficacy of increased LPV/r dosing regimens during pregnancy should be investigated.

040711
LbOrB08