title: Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia.
abstract: OBJECTIVE
  To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin.
  
  
  METHODS
  This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331).
  
  
  RESULTS
  Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months.
  
  
  CONCLUSIONS
  HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1.
authors.affiliation: Department of Paediatrics and Child Health, King Edward Hospital, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Prakash
authors.initials: P
authors.lastname: Jeena
authors.forename: Donald M
authors.initials: DM
authors.lastname: Thea
authors.forename: William B
authors.initials: WB
authors.lastname: MacLeod
authors.forename: Noel
authors.initials: N
authors.lastname: Chisaka
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fox
authors.forename: H M
authors.initials: HM
authors.lastname: Coovadia
authors.forename: Shamim
authors.initials: S
authors.lastname: Qazi
mesh_terms: D000658:Amoxicillin / Q000627:therapeutic use*; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000188:drug therapy; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D015337:Multicenter Studies as Topic; D010406:Penicillins / Q000627:therapeutic use*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D013019:South Africa / Q000453:epidemiology; D017211:Treatment Failure; D015024:Zambia / Q000453:epidemiology
chemical_list: D010406:Penicillins; D000658:Amoxicillin