Journal Article

High Risk of Neutropenia in HIV-Infected Children following Treatment with Artesunate plus Amodiaquine for Uncomplicated Malaria in Uganda

Anne F. Gasasira, Moses R. Kamya, Jane Achan, Tsedal Mebrahtu, Joan N. Kalyango, Theodore Ruel, Edwin Charlebois, Sarah G. Staedke, Adeodata Kekitiinwa, Philip J. Rosenthal, Diane Havlir and Grant Dorsey

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 46, issue 7, pages 985-991
Published in print April 2008 | ISSN: 1058-4838
Published online April 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/529192
High Risk of Neutropenia in HIV-Infected Children following Treatment with Artesunate plus Amodiaquine for Uncomplicated Malaria in Uganda

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Background. 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%; P=.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%; Pt;.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, t;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%; P=.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.

Journal Article.  4103 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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