743
Lopinavir Drug Monitoring in 36 Pregnant Women
Marie-Aude Khuong-Josses*1, A Boussaïri1, C Palette2, and D Méchali1
1Hosp Delafontaine, Saint-Denis, France and 2Ctr Hosp de Versailles, Le Chesnay, France
Background: Reduced lopinavir (LPV) exposure during pregnancy has been reported. However, whether the trough concentration (Cmin)
threshold is achieved at standard adult LPV/ritonavir (LTV/r) dosing (400 mg/100 mg) during the
third trimester is controversial.
Methods: At our outpatient HIV clinic, 36 HIV-infected pregnant women received
LPV/r 400/100 mg twice daily as part of a triple regimen. Drug plasma levels
were measured as part of routine clinical practice around 2 weeks after the
start of therapy or during the second or third trimester of pregnancy in women
on treatment before the pregnancy. LPV was measured by reverse-phase high
performance liquid chromatography/diode array detector (HPLC/DAD) with a limit
of 0.05 mg/L.
CD4
T-cell count and HIV plasma viral load were measured.
Results: LPV pharmacokinetic data were available for 36 women (33 black, 3 white; median age 32 years; median
weight 66
kg). The nucleoside reverse
transcriptase inhibitor (NRTI) backbone
was zidovudine (ZDV) + lamivudine
(3TC) in 29 (80%).
Median
gestation at LPV/r initiation was 25 weeks (range 10 to 34). Trough levels were
performed in the second trimester (n =
23) and in the third trimester (n = 19).
Average LPV trough concentration (Cmin)
was 5.30±2.73 mg/L (range 0.05 to 10.6). LPV Cmin
was below the recommended level (3 mg/L) in 3 women, all with adherence issues.
The mean trough LPV level in the second trimester was 6.13 mg/L and 5.10 mg/L
in the third trimester with no significant difference. In
women with detectable viral load (starting ART), median HIV viral load
decreased from 4.30 log10 to 1.84 log10, after a median
16 days from the start of the therapy. No correlation was found between
LPV Cmin and viral load decline. Of the 25
women with HIV plasma viral load at the time of delivery, 17 had undetectable
HIV viral load (<50 copies/mL), 22 had HIV viral
load <200 copies/mL and 3 had >200 copies/mL (280, 453, and 22,148 copies/mL).
Conclusions: In this cohort study, standard dosages of
plasma LPV seem to provide adequate levels of exposure and viral suppression. New tablet
formulation LPV/r should be
appropriate and may improve treatment adherence.
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