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

Clin Infect Dis. 2008 Apr 1;46(7):985-91. doi: 10.1086/529192.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

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


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