title: Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in HIV-positive pregnant women.
abstract: A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 μg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 μg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.).
authors.affiliation: Laboratório de Pesquisa Clínica em DST/AIDS, Instituto de Pesquisa Clínica Evandro Chagas (IPEC), Fundação Oswaldo Cruz (Fiocruz), Manguinhos, Rio de Janeiro, Brazil.
authors.forename: Marilia
authors.initials: M
authors.lastname: Santini-Oliveira
authors.forename: Rita de Cássia Elias
authors.initials: Rde C
authors.lastname: Estrela
authors.forename: Valdiléa Gonçalves
authors.initials: VG
authors.lastname: Veloso
authors.forename: Vitória Berg
authors.initials: VB
authors.lastname: Cattani
authors.forename: Carolyn
authors.initials: C
authors.lastname: Yanavich
authors.forename: Luciane
authors.initials: L
authors.lastname: Velasque
authors.forename: Thiago Silva
authors.initials: TS
authors.lastname: Torres
authors.forename: Luana Monteiro Spindola
authors.initials: LM
authors.lastname: Marins
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Pilotto
authors.forename: Esaú Custódio
authors.initials: EC
authors.lastname: João
authors.forename: José Carlos Saraiva
authors.initials: JC
authors.lastname: Gonçalves
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D061466:Lopinavir; D019438:Ritonavir