Determinants of HIV related mortality in African children on antiretroviral therapy: clinical and immunological insights from a systematic review and meta-analysis

BACKGROUND: The HIV epidemic in Africa is still a serious public health concern, particularly for children who are more vulnerable to its negative consequences. Various studies carried out in different African nations have shown associations between these variables and increased mortality risk in children receiving antiretroviral therapy. However, the magnitude and consistency of these effects across different settings in Africa remain unclear, with a few studies reporting nonsignificant effects of advanced disease stage and immunological factors on mortality. This review is the first to provide a thorough analysis of the determinants of HIV-related mortality in children. METHODS: This review followed the PRISMA guidelines, and relevant studies were obtained from the PubMed, CINAHL, EMBASE, and Google Scholar databases. Study selection, data extraction, and quality evaluation were carried out separately by two reviewers. A heterogeneity-based meta-analysis was conducted using random effect models. A sub group analysis was done based on age group and country. RESULTS: A total of 36 studies involving 198,957 study participants were included in the review. Advanced disease stage (WHO III/IV) (HR 3.45; 95% CI 2.17-5.48), TB coinfection (HR 2.12; 95% CI 1.53-2.92), opportunistic infections (HR 2.04; 95% CI 1.59-2.62), immunosuppression (HR 2.50; 95% CI 2.01-3.11), and poor medication adherence (HR 3.36; 95% CI 2.10-5.38) and lack of cotrimoxazole use (HR 2.2; 95% CI 1.14-4.26) were significantly associated with a greater risk of HIV-related mortality. CONCLUSION: This review revealed key clinical, immunological, and treatment-related predictors of HIV-related mortality in children in Africa, including advanced disease stage, TB co-infection, immunosuppression, poor adherence, and lack of cotrimoxazole use. To reduce HIV-related child mortality in Africa, health policies should strengthen pediatric HIV care through context-specific service delivery. This includes early identification of advanced disease, management of opportunistic infections, access to cotrimoxazole prophylaxis, and age-appropriate adherence support, especially in under-resourced settings

• Epidemiology and Determinants of Health
  • Epidemiology
• Population(s)
  • Children or Youth (less than 18 years old)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Treatment
• Co-infections
  • Tuberculosis
  • Other
• Health Systems
  • Governance arrangements
  • Delivery arrangements