title: 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.affiliation: Department of Internal Medicine, Makerere University, Mulago Hospital, Kampala, Uganda. agasasira@berkeley.edu
authors.forename: Anne F
authors.initials: AF
authors.lastname: Gasasira
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.forename: Tsedal
authors.initials: T
authors.lastname: Mebrahtu
authors.forename: Joan N
authors.initials: JN
authors.lastname: Kalyango
authors.forename: Theodore
authors.initials: T
authors.lastname: Ruel
authors.forename: Edwin
authors.initials: E
authors.lastname: Charlebois
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Staedke
authors.forename: Adeodata
authors.initials: A
authors.lastname: Kekitiinwa
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Diane
authors.initials: D
authors.lastname: Havlir
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D000077332:Artesunate; D018890:Chemoprevention; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007223:Infant; D008288:Malaria / Q000150:complications* / Q000188:drug therapy*; D009503:Neutropenia; D012717:Sesquiterpenes / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents; D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000655:Amodiaquine; D000077332:Artesunate; D015662:Trimethoprim, Sulfamethoxazole Drug Combination