Browsing by Author "Aweeka, Francesca"

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    Antiretroviral Agents and Prevention of Malaria in HIV-Infected Ugandan Children
    (The New England Journal of Medicine, 2012) Achan, Jane; Kakuru, Abel; Ikilezi, Gloria; Ruel, Theodore; Clark, Tamara D.; Nsanzabana, Christian; Charlebois, Edwin; Aweeka, Francesca; Dorsey, Grant; Rosenthal, Philip J.; Havlir, Diane; Kamya, Moses R
    Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV infected children would be lower among children receiving lopinavir–ritonavir– based antiretroviral therapy (ART) than among those receiving nonnucleosidereverse transcriptase inhibitor (NNRTI)–based ART.
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    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, 2021) Owor, Maxensia; Tierney, Camlin; Ziemba, Lauren; Browning, Renee; Moye, John; Graham, Bobbie; Reding, Christina; Costello, Diane; Norman, Jennifer; Wiesner, Lubbe; Hughes, Emma; Whalen, Meghan E.; Purdue, Lynette; Mmbaga, Blandina Theophil; Kamthunzi, Portia; Kawalazira, Rachel; Nathoo, Kusum; Bradford, Sarah; Coletti, Anne; Aweeka, Francesca; Musoke, Philippa
    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.
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    Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda
    (Antimicrobial agents and chemotherapy, 2010) Mwesigwa, Julia; Parikh, Sunil; McGee, Bryan; German, Polina; Drysdale, Troy; Kalyango, Joan N.; Clark, Tamara D.; Dorsey, Grant; Lindegardh, Niklas; Annerberg, Anna; Rosenthal, Philip J.; Kamya, Moses R.; Aweeka, Francesca
    The World Health Organization recommends the use of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. The two most widely adopted ACT regimens are artemether (AR)- lumefantrine (LR) (the combination is abbreviated AL) and amodiaquine (AQ)-artesunate (AS). Pharmacokinetic (PK) data informing the optimum dosing of these drug regimens is limited, especially in children. We evaluated PK parameters in Ugandan children aged 5 to 13 years with uncomplicated malaria treated with AL (n 20) or AQ-AS (n 21), with intensive venous sampling occurring at 0, 2, 4, 8, 24, and 120 h following administration of the last dose of 3-day regimens of AL (twice daily) or AQ-AS (once daily). AS achieved an estimated maximum concentration in plasma (Cmax) of 51 ng/ml and an area under the concentration-time curve from time zero to infinity (AUC0– ) of 113 ng h/ml; and its active metabolite, dihydroartemisinin (DHA), achieved a geometric mean Cmax of 473 ng/ml and an AUC0– of 1,404 ng h/ml. AR-DHA exhibited a Cmax of 34/119 ng/ml and an AUC0– of 168/382 ng h/ml, respectively. For LR, Cmax and AUC0– were 6,757 ng/ml and 210 g h/ml, respectively. For AQ and its active metabolite, desethylamodiaquine (DEAQ), the Cmaxs were 5.2 ng/ml and 235 ng/ml, respectively, and the AUC0– s were 39.3 ng h/ml and 148 g h/ml, respectively. Comparison of the findings of the present study to previously published data for adults suggests that the level of exposure to LR is lower in children than in adults and that the level of AQ-DEAQ exposure is similar in children and adults. For the artemisinin derivatives, differences between children and adults were variable and drug specific. The PK results generated for children must be considered to optimize the dosing strategies for these widely utilized ACT regimens.