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PLoS One. 2013 Dec 13;8(12):e83389. doi: 10.1371/journal.pone.0083389. eCollection 2013.

Validation and calibration of a computer simulation model of pediatric HIV infection.

Author information

  • 1Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
  • 2Division of General Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
  • 3Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Division of General Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; The Center for AIDS Research, Harvard University, Boston, Massachusetts, United States of America.
  • 4The Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • 5Department of Child Health and Pediatrics, Moi University, Eldoret, Kenya.
  • 6Inserm, Unit 897, Institut de Santé Publique et de Développement, Université Bordeaux Segalen 2, Bordeaux, France.
  • 7The Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • 8Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Children's Hospital Boston, Boston, Massachusetts, United States of America ; Department of Pediatrics, Division of Pediatric Infectious Diseases, University of California Los Angeles, Los Angeles, California, United States of America.
  • 9Division of General Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, and Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; The Center for AIDS Research, Harvard University, Boston, Massachusetts, United States of America ; The Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.
  • 10Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Division of General Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; The Center for AIDS Research, Harvard University, Boston, Massachusetts, United States of America ; The Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, United States of America ; The Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America.

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.

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