Pharmacokinetics and Safety of FPV/r in Pregnant HIV+ Women
Pharmacokinetics and Safety of FPV/r in Pregnant HIV+ Women
Steady-state pharmacokinetics in pregnant women prescribed ritonavir-boosted fosamprenavir (FPV) to prevent HIV transmission were assessed in the second trimester, third trimester, and postpartum. Compared with postpartum, geometric mean amprenavir (APV, FPVs active metabolite) area under the plasma concentration–time curves were 35% lower in the second trimester and 25% lower in the third trimester. Maternal APV concentrations were 9- to 15-fold above the mean APV protein-adjusted 50% inhibitory concentration for wild-type HIV. Median ratio of cord blood/maternal APV levels was 0.27, and all infants were HIV negative. FPV/ritonavir during pregnancy was well tolerated and led to virologic suppression.
The number of women of reproductive age living with HIV infection is increasing in worldwide and many of these women desire to have children. As guidelines evolve to initiate treatment at higher CD4 T-cell levels, the number of pregnant HIV-infected women receiving antiretroviral therapy can be expected to increase. The use of combination antiretroviral therapy during pregnancy has reduced the HIV transmission rate from approximately 20%–30% to <2% in developed countries. However, physiologic changes occurring during pregnancy can greatly alter the pharmacokinetics of antiretroviral drugs. Plasma concentrations of most protease inhibitors (PIs) have been reported to decrease during pregnancy. Increased doses are sometimes needed to ensure maintenance of virologic suppression in pregnancy with atazanavir, lopinavir/ritonavir (RTV), and saquinavir. This underscores the importance of optimizing treatment choices during pregnancy so as to prevent mother-to-child HIV transmission (p-MTCT) while minimizing the risks to both the mother and fetus.
The primary objective of this study was to assess the pharmacokinetics of fosamprenavir (FPV) boosted by RTV in pregnancy in the second and third trimesters compared with postpartum and to determine the transplacental transfer via cord blood/maternal amprenavir (APV) ratios.
Abstract and Introduction
Abstract
Steady-state pharmacokinetics in pregnant women prescribed ritonavir-boosted fosamprenavir (FPV) to prevent HIV transmission were assessed in the second trimester, third trimester, and postpartum. Compared with postpartum, geometric mean amprenavir (APV, FPVs active metabolite) area under the plasma concentration–time curves were 35% lower in the second trimester and 25% lower in the third trimester. Maternal APV concentrations were 9- to 15-fold above the mean APV protein-adjusted 50% inhibitory concentration for wild-type HIV. Median ratio of cord blood/maternal APV levels was 0.27, and all infants were HIV negative. FPV/ritonavir during pregnancy was well tolerated and led to virologic suppression.
Introduction
The number of women of reproductive age living with HIV infection is increasing in worldwide and many of these women desire to have children. As guidelines evolve to initiate treatment at higher CD4 T-cell levels, the number of pregnant HIV-infected women receiving antiretroviral therapy can be expected to increase. The use of combination antiretroviral therapy during pregnancy has reduced the HIV transmission rate from approximately 20%–30% to <2% in developed countries. However, physiologic changes occurring during pregnancy can greatly alter the pharmacokinetics of antiretroviral drugs. Plasma concentrations of most protease inhibitors (PIs) have been reported to decrease during pregnancy. Increased doses are sometimes needed to ensure maintenance of virologic suppression in pregnancy with atazanavir, lopinavir/ritonavir (RTV), and saquinavir. This underscores the importance of optimizing treatment choices during pregnancy so as to prevent mother-to-child HIV transmission (p-MTCT) while minimizing the risks to both the mother and fetus.
The primary objective of this study was to assess the pharmacokinetics of fosamprenavir (FPV) boosted by RTV in pregnancy in the second and third trimesters compared with postpartum and to determine the transplacental transfer via cord blood/maternal amprenavir (APV) ratios.
