title: Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children.
abstract: BACKGROUND
  Artemisinin combination therapy has become the standard of care for uncomplicated malaria in most of Africa. However, there is limited data on the safety and tolerability of these drugs, especially in young children and patients co-infected with HIV.
  
  
  METHODS
  A longitudinal, randomized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4-22 months in Tororo, Uganda. Participants were randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes. Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment. This study was registered in ClinicalTrials.gov (registration # NCT00527800).
  
  
  RESULTS
  A total of 122 children were randomized to AL and 124 to DP, resulting in 412 and 425 treatments, respectively. Most adverse events were rare, with only cough, diarrhoea, vomiting, and anaemia occurring in more than 1% of treatments. There were no differences in the risk of these events between treatment groups. Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms. Retreatment for malaria within 17-28 days was associated with an increased risk of vomiting in the DP treatment arm (HR = 6.47, 95% CI 2.31-18.1, p < 0.001). There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis.
  
  
  CONCLUSIONS
  Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00527800; http://clinicaltrials.gov/ct2/show/NCT00527800.
authors: Oregon Health and Science University, Portland, USA. katraks@ohsu.edu
authors: Shereen
authors: S
authors: Katrak
authors: Anne
authors: A
authors: Gasasira
authors: Emmanuel
authors: E
authors: Arinaitwe
authors: Abel
authors: A
authors: Kakuru
authors: Humphrey
authors: H
authors: Wanzira
authors: Victor
authors: V
authors: Bigira
authors: Taylor G
authors: TG
authors: Sandison
authors: Jaco
authors: J
authors: Homsy
authors: Jordan W
authors: JW
authors: Tappero
authors: Moses R
authors: MR
authors: Kamya
authors: Grant
authors: G
authors: Dorsey
mesh_terms: D000962:Antimalarials / Q000009:adverse effects*; D000077549:Artemether; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects*; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D011804:Quinolines / Q000009:adverse effects*; D012307:Risk Factors; D016896:Treatment Outcome; D014454:Uganda; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000077549:Artemether; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines