Peer-reviewed article
Risk and Protective Factors Associated With HIV-Related Mortality in Children Receiving Antiretroviral Therapy: A Model-Based Meta-Regression.
Jiawei He, Reshma Kassanjee, Amanda Movo, Magdalene K Walters, Edmond Brewer et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This meta-regression analysis of 67 cohort studies examined what country-level factors are associated with HIV-related death in children receiving antiretroviral therapy. The study found that access to improved water, pneumococcal vaccine coverage, and maternal education were the three strongest protective factors linked to lower mortality. The findings suggest that integrated public health strategies addressing water, vaccination, and maternal education—alongside HIV treatment—may help reduce deaths among children living with HIV in resource-limited settings.
Key points
- A 10% increase in improved water access was associated with 17% lower odds of HIV-related mortality (OR 0.83)
- A 10% increase in pneumococcal conjugate vaccine third-dose coverage was associated with 2% lower odds of mortality (OR 0.980)
- A 10% increase in maternal education was associated with lower odds of mortality (OR 0.997)
- Protective associations were stronger with 20% increases in these three factors
- Mortality disparities between resource-limited and resource-rich settings remain substantial despite ART access
Limitations
This is a country-level ecological analysis using aggregated data, so it cannot identify causal mechanisms or individual-level risk factors. The analysis depends on the quality and completeness of data from the 67 included cohort studies, which may vary by setting.
Abstract
IMPORTANCE: Mortality among children and young adolescents receiving antiretroviral therapy (ART) remains substantially higher in resource-limited settings compared with resource-rich regions. The role of modifiable risk and protective factors in explaining this global variation remains poorly understood. OBJECTIVE: To identify and quantify country-level modifiable risk and protective factors associated with HIV-related mortality among children and young adolescents receiving ART. DESIGN, SETTING, AND PARTICIPANTS: This model-based meta-regression analysis linked HIV-related mortality data from cohort studies included in a published systematic review of children and adolescents (aged 0-14 years) receiving ART, with biomedical, behavioral, and structural factors from the Global Burden of Diseases, Injuries, and Risk Factors study 2023. Data were analyzed using penalized regression (ridge regression with cross-validation) and an ensemble machine-learning algorithm (XGBoost). Study data were analyzed from August 2024 to October 2025. EXPOSURES: Country-level modifiable covariates, including access to improved water, vaccine coverage against different pathogens, maternal education, underweight proportion, and oral rehydration coverage. MAIN OUTCOMES AND MEASURES: Measures included the odds ratios (ORs) of HIV-related mortality while receiving ART associated with modifiable factors, simulations of hypothetical 10% and 20% increases in covariates, and variable importance via Shapley Additive Explanation (SHAP) values. RESULTS: HIV-related mortality data from 67 cohort studies were included in this analysis. Access to improved water, pneumococcal conjugate vaccine third-dose (PCV3) coverage, and maternal education demonstrated the strongest independent associations with HIV-related mortality while receiving ART. A 10% increase in improved water access, PCV3 coverage, and maternal education was associated with lower odds of mortality (OR, 0.83; 95% CI, 0.826-0.843; OR, 0.980; 95% CI, 0.972-0.987; and OR, 0.997; 95% CI, 0.996-0.998, respectively). At 20% increases, these protective associations with HIV-related mortality were stronger (OR, 0.695; 95% CI, 0.682-0.711; OR, 0.959; 95% CI, 0.945-0.974; and OR, 0.994; 95% CI, 0.992-0.997, respectively). SHAP-based analyses consistently ranked these 3 factors as most predictive of HIV-related mortality. CONCLUSIONS AND RELEVANCE: Findings of this model-based meta-regression analysis show that improved water access, PCV3 coverage, and maternal education were associated with lower HIV-related mortality among children receiving ART, underscoring the need for integrated public health strategies beyond ART alone. Interventions to strengthen water infrastructure, vaccination programs, and maternal education may help reduce global survival disparities among children and adolescents living with HIV and receiving ART.