Abstract:
Background: Computer simulation models can project long-term patient outcomes and inform health policy. We
internally validated and then calibrated a model of HIV disease in children before initiation of antiretroviral therapy to
provide a framework against which to compare the impact of pediatric HIV treatment strategies.
Methods: We developed a patient-level (Monte Carlo) model of HIV progression among untreated children <5 years
of age, using the Cost-Effectiveness of Preventing AIDS Complications model framework: the CEPAC-Pediatric
model. We populated the model with data on opportunistic infection and mortality risks from the International
Epidemiologic Database to Evaluate AIDS (IeDEA), with mean CD4% at birth (42%) and mean CD4% decline (1.4%/
month) from the Women and Infants’ Transmission Study (WITS). We internally validated the model by varying
WITS-derived CD4% data, comparing the corresponding model-generated survival curves to empirical survival
curves from IeDEA, and identifying best-fitting parameter sets as those with a root-mean square error (RMSE) <0.01.
We then calibrated the model to other African settings by systematically varying immunologic and HIV mortality-
related input parameters. Model-generated survival curves for children aged 0-60 months were compared, again
using RMSE, to UNAIDS data from >1,300 untreated, HIV-infected African children.
Results: In internal validation analyses, model-generated survival curves fit IeDEA data well; modeled and observed
survival at 16 months of age were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4%
parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4% was 45% at birth and declined by
6%/month (ages 0-3 months) and 0.3%/month (ages >3 months). In calibration analyses, increases in IeDEA-derived
mortality risks were necessary to fit UNAIDS survival data.
Conclusions: The CEPAC-Pediatric model performed well in internal validation analyses. Increases in modeled
mortality risks required to match UNAIDS data highlight the importance of pre-enrollment mortality in many pediatric
cohort studies.
