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Treatment Failures and Excess Mortality Among HIV-Exposed, Uninfected Children With Pneumonia
Matthew S Kelly1, Kathleen E Wirth2, Andrew P Steenhoff3
1Botswana-UPenn Partnership, Gaborone, Botswana Divisions of Global Health Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, North Carolina.
Insights
Human immunodeficiency virus (HIV)-exposed, uninfected (HIV-EU) infants under 6 months face higher pneumonia treatment failure and mortality. Standard cephalosporin treatment did not improve outcomes in this vulnerable group.
Area of Science:
- Pediatrics
- Infectious Diseases
- Public Health
Background:
- Human immunodeficiency virus (HIV)-exposed, uninfected (HIV-EU) children face increased risks of infections and mortality.
- Treatment outcomes for lower respiratory tract infections in HIV-EU children are not well-defined.
Purpose of the Study:
- To investigate treatment outcomes for pneumonia in HIV-EU children.
- To compare treatment failure and mortality rates between HIV-EU and HIV-unexposed children.
Main Methods:
- A prospective cohort study of 238 children aged 1-23 months with WHO-defined pneumonia in Botswana.
- Primary outcome: treatment failure at 48 hours, assessed by a blinded investigator.
- Secondary outcome: in-hospital mortality.
Main Results:
- HIV-EU children had higher treatment failure rates (47% vs. 24%) and in-hospital mortality (RR: 4.31) compared to HIV-unexposed children.
- These disparities were significant only in children under 6 months of age.
- Third-generation cephalosporin use did not reduce treatment failure risk in HIV-EU children.
Conclusions:
- HIV-EU children under 6 months with pneumonia experience worse outcomes, including higher treatment failure and mortality.
- Current antibiotic regimens, including third-generation cephalosporins, may not be sufficient for this population.
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.
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