High Risk of Neutropenia in HIV-Infected Children following Treatment with Artesunate plus Amodiaquine for Uncomplicated Malaria in Uganda
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Date
2008
Authors
Gasasira, Anne F.
Kamya, Moses R.
Achan, Jane
Mebrahtu, Tsedal
Kalyango, Joan N.
Ruel, Theodore
Charlebois, Edwin
Staedke, Sarah G.
Kekitiinwa, Adeodata
Rosenthal, Philip J.
Journal Title
Journal ISSN
Volume Title
Publisher
Clinical infectious diseases
Abstract
Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria
in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus
(HIV)–infected populations.
Methods. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected
children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate
plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received
trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines.
Results. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected
children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were
receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious
in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively);
however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9%
vs. 13.2%; Pp.08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus
amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; P !
.001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of
episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, !750 cells/
mm3). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received
antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; Pp.001).
Conclusions. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children
but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use.
Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected
individuals.
Description
Keywords
Neutropenia, HIV-Infected Children, Treatment, Artesunate plus Amodiaquine, Malaria, Uganda
Citation
Gasasira, A. F., Kamya, M. R., Achan, J., Mebrahtu, T., Kalyango, J. N., Ruel, T., ... & Dorsey, G. (2008). High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. Clinical infectious diseases, 46(7), 985-991. DOI: 10.1086/529192