Reduced Lopinavir Exposure during Pregnancy: A Case Control Study
Gilles Peytavin*1, S Pierre-François2, B Cassard1, P de Truchis3, C Winter4, B Visseaux1, F Damond1, R Tubiana5, L Mandelbrot6, and S Matheron1
1Hosp Bichat-Claude Bernard, Paris, France; 2Zobda Quitman Hosp, Fort de France, France; 3Hosp Raymond Poincare, Garches, France; 4Hosp Montreuil, France; 5Hosp Pitie-Salpetriere, Paris, France; and 6Hosp L Mourier, Colombes, France
Background: ART in HIV-infected pregnant
women is primarily indicated to prevent HIV vertical transmission and is
stopped after delivery in most cases. Therefore, the effect of the
physiological changes associated with pregnancy on drug pharmacokinetics is
difficult to assess in a pharmacokinetic ante- and post-partum comparison. Our objective was to describe
lopinavir (LPV) plasma concentrations and virological outcomes in HIV-infected
Methods: This was a prospective, multi-center case/control study enrolling 100 consecutive
HIV-infected pregnant women who received LPV/ritonavir
(r or RTV) 400/100 mg twice dialy and 2 nucleoside
reverse transcriptase inhibitors (NRTI). CD4 cell count and plasma HIV RNA
(median, IQR 25 to 75) were available at delivery. LPV Cmin was
determined using high performance liquid chromatography (HPLC) coupled with
photodiode array-ultraviolet (PDA-UV) detection (limit of quantitation
30 ng/mL) during the second or third trimester. LPV Cmin
were matched to results of non-pregnant women (control group) according to age,
stable LPV/r 400/100 mg twice daily treatment and plasma viral load <200
copies/mL at the time of pharmacokinetic assay.
Statistical analysis was performed using Mann Whitney and spearman tests.
Results: We enrolled 101 pregnant women
(aged 32 years, 28 to 35). At delivery, CD4 counts were 416/mm3 (334
to 529) and plasma viral load <200 copies/mL in
85%. At second and third trimester, LPV Cmin were 3806 ng/mL (2765 to 5640; n
= 27) and 3274 ng/mL (1792 to 4501; n = 74), respectively (p = 0.055). No drug adjustments were
performed in these patients. LPV Cmin at second and third trimester
were statistically correlated to plasma viral load at delivery (p = 0.0005). There was also a
statistical correlation between LPV and RTV Cmin. In patients with
plasma viral load <200 copies/mL, LPV Cmin was statistically higher in the control
group (5122 ng/mL; 3440 to 7496; n = 107) than at second and third trimester in pregnant patients (p = 0.03 and p <0.0001).
Conclusions: LPV exposure during pregnancy is
lower than in non-pregnant women, particularly during the third trimester.
Inadequate viral suppression observed at delivery may be predicted by low LPV Cmin.
In such cases, a dose increase of LPV/r should be proposed in these patients.