Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092

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dc.contributor.authorOwor, Maxensia
dc.contributor.authorTierney, Camlin
dc.contributor.authorZiemba, Lauren
dc.contributor.authorBrowning, Renee
dc.contributor.authorMoye, John
dc.contributor.authorGraham, Bobbie
dc.contributor.authorReding, Christina
dc.contributor.authorCostello, Diane
dc.contributor.authorNorman, Jennifer
dc.contributor.authorWiesner, Lubbe
dc.contributor.authorHughes, Emma
dc.contributor.authorWhalen, Meghan E.
dc.contributor.authorPurdue, Lynette
dc.contributor.authorMmbaga, Blandina Theophil
dc.contributor.authorKamthunzi, Portia
dc.contributor.authorKawalazira, Rachel
dc.contributor.authorNathoo, Kusum
dc.contributor.authorBradford, Sarah
dc.contributor.authorColetti, Anne
dc.contributor.authorAweeka, Francesca
dc.contributor.authorMusoke, Philippa
dc.date.accessioned2022-03-08T10:46:29Z
dc.date.available2022-03-08T10:46:29Z
dc.date.issued2021
dc.description.abstractSevere acute malnutrition (SAM) may alter the pharmacokinetics (PK), efficacy, and safety of antiretroviral therapy. The phase IV study, IMPAACT P1092, compared PK, safety, and tolerability of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in children with and without SAM. Materials and methods: Children living with HIV 6 to <36 months of age with or without World Health Organization (WHO)-defined SAM received ZDV, 3TC, and LPV/r syrup for 48 weeks according to WHO weight band dosing. Intensive PK sampling was performed at weeks 1, 12, and 24. Plasma drug concentrations were measured using liquid chromatography tandem mass spectrometry. Steady-state mean area under the curve (AUC0–12h) and clearance (CL/F) for each drug were compared. Grade ≥3 adverse events were compared between cohorts. Results: Fifty-two children were enrolled across 5 sites in Africa with 44% (23/52) female, median age 19 months (Q1, Q3: 13, 25). Twenty-five children had SAM with entry median weight-for-height Z-score (WHZ) −3.4 (IQR −4.0, −3.0) and 27 non-SAM had median WHZ −1.0 (IQR −1.8, −0.1). No significant differences in mean AUC0–12h or CL/F were observed (P ≥ 0.09) except for lower 3TC AUC0–12h (GMR, 0.60; 95% CI, 0.4–1.0; P = 0.047) at week 12, higher ZDV AUC0–12h (GMR, 1.52; 1.2–2.0; P = 0.003) at week 24 in the SAM cohort compared with non-SAM cohort. Treatment-related grade ≥3 events did not differ significantly between cohorts (24.0% vs. 25.9%). Conclusion: PK and safety findings for ZDV, 3TC, and LPV/r support current WHO weight band dosing of syrup formulations in children with SAM.en_US
dc.identifier.citationOwor, M., Tierney, C., Ziemba, L., Browning, R., Moye, J., Graham, B., ... & Musoke, P. (2021). Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092. The Pediatric Infectious Disease Journal, 40(5), 446. DOI: 10.1097/INF.0000000000003055en_US
dc.identifier.issn0891-3668/21/4005-0446
dc.identifier.other10.1097/INF.0000000000003055
dc.identifier.urihttps://nru.uncst.go.ug/xmlui/handle/123456789/2555
dc.language.isoenen_US
dc.publisherThe Pediatric Infectious Disease Journalen_US
dc.subjectPharmacokineticsen_US
dc.subjectHIVen_US
dc.subjectSevere acute malnutritionen_US
dc.subjectChildrenen_US
dc.subjectLopinavir/Ritonaviren_US
dc.titlePharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092en_US
dc.typeArticleen_US
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