Reduced lopinavir exposure during pregnancy

Abstract

LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated.

The relation between treatment outcome and efavirenz, atazanavir or lopinavir exposure in the NORTHIV trial of treatment-naïve HIV-1 infected patients

“…Yet, even though it is rare that adherent patients with LPV/r 400/100 mg b.i.d. have troughs below this level, the issue of the-hitherto undefined-lower efficacy target of LPV is of substantial importance in a range of clinical situations, such as in relation to the higher oral clearance seen in pregnancy, and the consequent question of the appropriate dose of LPV under these circumstances [38]. In our view, the question of the minimal effective concentration for LPV in treatmentnaïve patients remains unanswered.…”

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

“…[13][14][15] In the PROMISE trial, the lopinavir-ritonavir dose was increased during the third trimester because pharmacokinetic studies showed decreased lopinavir-ritonavir levels with standard doses in late pregnancy. 16,17 The ART regimens in the PROMISE trial were protease inhibitor-based because nevirapinebased ART was contraindicated in women with a CD4 count of more than 250 cells per cubic millimeter, and efavirenz, the other available nonnucleoside reverse-transcriptase inhibitor (NNRTI), was contraindicated in pregnancy at that time. There are inconsistent findings regarding protease inhibitor-based ART and preterm delivery.…”

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

“…5,6 It has been suggested that concentrations of lopinavir below 1000 ng/mL are not adequate for suppression of wild-type virus, 8 and although studies have not provided a cut-off value, there have been positive correlations between lipid profiles 9 and liver enzyme elevation 10 and lopinavir pharmacokinetics. There is currently a lack of pharmacokinetic data in HIVinfected pregnant women and as such 'therapeutic' levels of lopinavir are based on data obtained from a Caucasian male cohort (University of Liverpool, unpublished data).…”

“…Days on LPV/r at sampling 19 Hours since last dose 12 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) VL at trough sampling (copies/mL) 182 (40-252,000)…”