Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir

Abstract

SummaryThe pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence.

Prediction of area under the concentration–time curve for lopinavir from peak or trough lopinavir concentrations in patients receiving lopinavir–ritonavir therapy

“…Caswell et al 57 performed a population pharmacokinetic study that included sparse samples obtained from at least 23 patients and data from 5 patients who had a complete pharmacokinetic profile established. The visualization of the individual profiles suggested that the C 4hr data would reasonably represent the true peak value.…”

Therapeutic Drug Monitoring in Pregnancy

“…52 TDM is recommended for nonnucleoside reverse transcriptase inhibitors and PIs but not for nucleoside reverse transcriptase inhibitors as the plasma concentrations of nucleoside reverse transcriptase inhibitors correlate poorly with clinical response. 43,49 Exposure to subtherapeutic concentrations of antiretroviral agents during pregnancy could lead to therapeutic failure 43,52 and virological mutations.…”

“…52 TDM is recommended for nonnucleoside reverse transcriptase inhibitors and PIs but not for nucleoside reverse transcriptase inhibitors as the plasma concentrations of nucleoside reverse transcriptase inhibitors correlate poorly with clinical response. 43,49 Exposure to subtherapeutic concentrations of antiretroviral agents during pregnancy could lead to therapeutic failure 43,52 and virological mutations. 43 However, an association between lower antiretroviral plasma concentrations during pregnancy and treatment failure and virological breakthroughs has not been consistently demonstrated, 43,48 and there is a lack of large-scale studies showing that TDM improves clinical outcome.…”

“…43 However, an association between lower antiretroviral plasma concentrations during pregnancy and treatment failure and virological breakthroughs has not been consistently demonstrated, 43,48 and there is a lack of large-scale studies showing that TDM improves clinical outcome. 52 In summary, the pharmacokinetic variations in pregnancy, and in some cases the possibility of nonadherence, suggest a possible role for routine TDM of select medications such as lamotrigine and lithium during pregnancy and especially in women who are not optimally responding to therapy. However, for many medications for which dosing adjustment may be required during pregnancy, a target therapeutic range or concentration has not been defined or an assay is not practically available.…”

Enhanced Eryptosis Following Exposure to Lopinavir

“…The protease inhibitor lopinavir is used for the treatment of HIV infections [1][2][3][4][5][6][7][8][9][10][11][12][13]. Side effects of lopinavir treatment include anemia [14].…”