Pharmacokinetics and virologic response of zidovudine/lopinavir/ritonavir initiated during the third trimester of pregnancy.
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.


METHODS
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 300 mg zidovudine and 400/100 mg 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 microg 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/microl and HIV-1 RNA viral load 7818 (<40-402 015) copies/ml. Geometric mean (90% confidence interval) LPV AUC, Cmax and Cmin were 64.6 (59.7-69.8) microg h/ml, 8.1 (7.5-8.7) microg/ml and 2.7 (2.4-3.0) microg/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.


CONCLUSIONS
A short course of zidovudine plus standard-dose LPV/r initiated during the third trimester of pregnancy achieved adequate LPV exposure and virologic response.
Cressey
Tim R
TR
Department of Medical Technology, Chiang Mai University, Thailand. tim@phpt.org
Jourdain
Gonzague
G
Rawangban
Boonsong
B
Varadisai
Supang
S
Kongpanichkul
Rucha
R
Sabsanong
Prapan
P
Yuthavisuthi
Prapap
P
Chirayus
Somnuk
S
Ngo-Giang-Huong
Nicole
N
Voramongkol
Nipunporn
N
Pattarakulwanich
Somsak
S
Lallemant
Marc
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061466:Lopinavir; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013785:Thailand / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D015215:Zidovudine; D019438:Ritonavir