High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda

Gasasira, AF; Kamya, MR; Achan, J; Mebrahtu, T; Kalyango, JN; Ruel, T; Charlebois, E; Staedke, SG; Kekitiinwa, A; Rosenthal, PJ; Havlir, D; 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). pp. 985-991. ISSN 1058-4838 DOI: https://doi.org/10.1086/529192

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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%;). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus P = .08 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/mm(3)). 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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Malaria Centre
PubMed ID: 18444813
Web of Science ID: 253817800004
URI: http://researchonline.lshtm.ac.uk/id/eprint/8040


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