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

Abstract

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%; 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.

• Authors: 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, Grant Dorsey
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 46 Issue 7 Pg. 985-91 (Apr 01 2008) ISSN: 1537-6591 [Electronic] United States
• PMID: 18444813 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Anti-HIV Agents
• Antimalarials
• Artemisinins
• Sesquiterpenes
• Amodiaquine
• Artesunate
• Trimethoprim, Sulfamethoxazole Drug Combination

Topics

• Amodiaquine (adverse effects, therapeutic use)
• Anti-HIV Agents (therapeutic use)
• Antimalarials (adverse effects, therapeutic use)
• Artemisinins (adverse effects, therapeutic use)
• Artesunate
• Chemoprevention
• Child
• Child, Preschool
• Drug Therapy, Combination
• HIV Infections (complications, drug therapy)
• Humans
• Infant
• Malaria (complications, drug therapy)
• Neutropenia
• Sesquiterpenes (adverse effects, therapeutic use)
• Treatment Outcome
• Trimethoprim, Sulfamethoxazole Drug Combination (therapeutic use)
• Uganda