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 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 μg 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/μl 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) μg h/ml, 8.1 (7.5–8.7) μg/ml and 2.7 (2.4–3.0) μg/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.
aProgram for HIV Prevention and Treatment (PHPT), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
bDepartment of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
cInstitut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France
dNopparat Rajathanee Hospital, Bangkok, Thailand
eSamutsakhon Hospital, Samutsakhon, Thailand
fNakhonpathom Hospital, Nakhonpathom, Thailand
gSamutprakarn Hospital, Samutprakarn, Thailand
hPrapokklao Hospital, Chantaburi, Thailand
iVachira Phuket Hospital, Phuket, Thailand
jDepartment of Health, Ministry of Public Health, Nonthaburi, Thailand.
Received 28 April, 2010
Revised 25 May, 2010
Accepted 6 June, 2010
Correspondence to Tim R. Cressey, Program for HIV Prevention and Treatment (PHPT-IRD174), Department of Medical Technology, Faculty of Associated Medical Sciences, 6th Floor, 110 Inthawaroros Road, Muang Chiang Mai 50200, Thailand. Tel: +66 53 894 431; fax: +66 53 894 220; e-mail: firstname.lastname@example.org