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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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
The Pediatric Infectious Disease Journal
Abstract
Severe 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.
Description
Keywords
Pharmacokinetics, HIV, Severe acute malnutrition, Children, Lopinavir/Ritonavir
Citation
Owor, 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.0000000000003055