Lopinavir/r levels reduced during pregnancy

Pregnancy can alter the pharmacokinetics (PK) of antiretrovirals and it is well known that optimal exposure during pregnancy is essential both for maternal health and preventing mother to child transmission.

In an oral late breaker, Alice Stek presented preliminary findings from a small sub study of PACTG 1026 – an ongoing study of PK in HIV-infected women.

This study compared data from intensive PK profiles (over 12 hours) performed at 30-36 weeks gestation obtained from 12 women receiving lopinavir/ritonavir 400/100mg twice daily to non-pregnant controls and to post partum measurements at 6-12 weeks (available for 4 women). Maternal and cord blood samples were also obtained at delivery.

Target LPV AUC was >10th percentile (52mcg*hr/mL) and the investigators reported that 10 of the 12 women did not reach this target – the average antepartum LPV AUC was 44+- 17mcg*hr/mg (95%CI 34-54). Of the 4 women for which post partum evaluations were available 1/4 did not reach the target LPV AUC. Maternal and cord blood samples were available for 5 maternal infant pairs and these revealed an average foetal exposure of 23% of maternal LPV concentration indicating that only small amounts of LPV appear to cross the placenta.

Findings from this small study suggest lower LPV exposure during the third trimester of pregnancy compared to non-pregnant controls and to post partum exposure. Dr Stek explained that this ongoing study would be modified to enrol women in the second trimester to investigate increased dosing of LPV/r in pregnancy.

Stek A, Mirochnick M, Capparelli E et al. Reduced lopinavir exposure during pregnancy: preliminary pharmacokinetic results from PACTG 1026. XV Intl AIDS Conference, Bangkok. Abstract LbOrB08