Résumé
Objective: To evaluate the pharmacokinetics and HIV viral load response following initiation during the third trimester of pregnancy of zidovudine plus standard-dose lopinavir boosted with ritonavir (LPV/r), twice daily, until delivery for the prevention of mother-to-child transmission of HIV.
Design: Prospective study nested within a multicenter, three-arm, randomized, phase III prevention of mother-to-child transmission of HIV trial in Thailand (PHPT-5, ClinicalTrials.gov Identifier: NCT00409591).
Methods: Women randomized to receive 300mg zidovudine and 400/100mg LPV/r twice daily from 28 weeks' gestation, or as soon as possible thereafter, until delivery had intensive steady-state 12-h blood sampling performed. LPV/r pharmacokinetic parameters were calculated using noncompartmental analysis. Rules were defined a priori for a LPV/r dose escalation based on the proportion of women with an LPV area under the concentration-time curve (AUC) below 52 mu g h/ml (10th percentile for LPV AUC in nonpregnant adults). HIV-1 RNA response was assessed during the third trimester.
Results: Thirty-eight women were evaluable; at entry, median (range) gestational age was 29 (28-36) weeks, weight 59.5 (45.0-91.6) kg, CD4 cells count 442 (260-1327) cells/mu l and HIV-1 RNA viral load 7818 (<40-402 015) copies/ml. Geometric mean (90% confidence interval) LPV AUC, C(max) and C(min) were 64.6 (59.7-69.8) mu g h/ml, 8.1 (7.5-8.7) mu g/ml and 2.7 (2.4-3.0) mu g/ml, respectively. Thirty-one of 38 (81%) women had an LPV AUC above the AUC target. All women had a HIV-1 viral load less than 400 copies/ml at the time of delivery.
Conclusion: A short course of zidovudine plus standard-dose LPV/r initiated during the third trimester of pregnancy achieved adequate LPV exposure and virologic response. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins