title: Treatment Failures and Excess Mortality Among HIV-Exposed, Uninfected Children With Pneumonia.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-exposed, uninfected (HIV-EU) children are at increased risk of infectious illnesses and mortality compared with children of HIV-negative mothers (HIV-unexposed). However, treatment outcomes for lower respiratory tract infections among HIV-EU children remain poorly defined.
  
  
  METHODS
  We conducted a hospital-based, prospective cohort study of N = 238 children aged 1-23 months with pneumonia, defined by the World Health Organization. Children were recruited within 6 hours of presentation to a tertiary hospital in Botswana. The primary outcome--treatment failure at 48 hours--was assessed by an investigator blinded to HIV exposure status.
  
  
  RESULTS
  Median age was 6.0 months; 55% were male. One hundred fifty-three (64%) children were HIV-unexposed, 64 (27%) were HIV-EU, and 20 (8%) were HIV-infected; the HIV exposure status of 1 child could not be established. Treatment failure at 48 hours occurred in 79 (33%) children, including in 36 (24%) HIV-unexposed, 30 (47%) HIV-EU, and 12 (60%) HIV-infected children. In multivariable analyses, HIV-EU children were more likely to fail treatment at 48 hours (risk ratio [RR]: 1.83, 95% confidence interval [CI]: 1.27-2.64, P = .001) and had higher in-hospital mortality (RR: 4.31, 95% CI: 1.44-12.87, P = .01) than HIV-unexposed children. Differences in outcomes by HIV exposure status were observed only among children under 6 months of age. HIV-EU children more frequently received treatment with a third-generation cephalosporin, but this did not reduce the risk of treatment failure in this group.
  
  
  CONCLUSIONS
  HIV-EU children with pneumonia have higher rates of treatment failure and in-hospital mortality than HIV-unexposed children during the first 6 months of life. Treatment with a third-generation cephalosporins did not improve outcomes among HIV-EU children.
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana Divisions of Global Health Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, North Carolina.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Kelly
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wirth
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana Divisions of Global Health Infectious Diseases, The Children's Hospital of Philadelphia, Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Steenhoff
authors.affiliation: Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, North Carolina.
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Tonya
authors.initials: T
authors.lastname: Arscott-Mills
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Sefelani C
authors.initials: SC
authors.lastname: Boiditswe
authors.affiliation: University of Botswana School of Medicine, Gaborone.
authors.forename: Mohamed Z
authors.initials: MZ
authors.lastname: Patel
authors.affiliation: Divisions of Hospital Medicine and Infectious Diseases, Cincinnati Children's Hospital Medical Center, Ohio.
authors.forename: Samir S
authors.initials: SS
authors.lastname: Shah
authors.affiliation: Divisions of Global Health Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Finalle
authors.affiliation: Ministry of Health, Gaborone, Botswana.
authors.forename: Ishmael
authors.initials: I
authors.lastname: Makone
authors.affiliation: Divisions of Global Health Infectious Diseases, The Children's Hospital of Philadelphia, Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Feemster
mesh_terms: D001902:Botswana; D005260:Female; D015658:HIV Infections; D006679:HIV Seropositivity / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D008297:Male; D011014:Pneumonia / Q000401:mortality* / Q000628:therapy*; D011446:Prospective Studies; D062606:Tertiary Care Centers; D017211:Treatment Failure
keywords: HIV-exposed; pneumonia; treatment outcomes; uninfected