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
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