Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study

Abstract

Background: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.

Methods: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria.

Findings: The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001).

Interpretation: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings.

Funding: National Institute of Health Fogarty International Center.

Figure 1:. STROBE diagram of record identification and exclusions from the primary analysis

ART=antiretroviral therapy. CALHIV=children and adolescents living with HIV.

Figure 2:. Relationship between continuous variables included in the models and the log odds of the outcome of interest (death within one year of ART initiation)

ART=antiretroviral therapy. WBC=white blood cells.

Figure 3:. Test set receiver operating characteristic curves displaying the AUC for the laboratory-based, exam-based, and advanced HIV continuous models compared with the WHO advanced HIV criteria for the complete cohort (A), children aged 0–11 years (B), and children aged 0–4 years (C)

The receiver operating characteristic curves are supported by the table showing the numerical AUC, 95% CI, and a comparison using the DeLong test of the various models with adjustment for multiple comparisons using the Holm method. AUC=area under the curve.