HIV-Associated TB Among Children and Adolescents in TB/HIV High Burden Settings: Trends and Risk Factors in the Era of Increasing ART Coverage

Abstract

Background: Children and adolescents living with human immune-deficiency virus (C/ALHIV) have increased tuberculosis (TB) risk compared to HIV-negative peers. Anti-retroviral therapy (ART) reduces TB risk among adults living with HIV, but data is limited in C/ALHIV. Methods: Patient data from seven pediatric HIV centers that adhere to national guidelines in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda were analyzed. Standardized HIV and TB classification and outcomes were reported following WHO guidelines. A Bayesian mixed effects model assessed association between ART coverage and TB period prevalence. Findings: The analytic period (2013-2017) encompassed 57,525 patient-years and captured 1,217 cases of HIV-associated child and adolescent TB. Favorable TB outcomes were associated with increased length of time in care and early ART initiation. Severe immunosuppression at TB diagnosis was associated with death. The TB incidence was 2,017/100,000 patient-years. With every 10% increase in C/ALHIV receiving ART, there was a 2.33% (95% Credible interval; 0.58%-4.40%) reduction in TB prevalence. Clinics with lower TB prevalence experienced less dramatic declines in TB incidence. Interpretation: These findings support continued need to advocate for policies and implement practices that optimize integrated pediatric and adolescent HIV and TB services. Although ART use is associated with decreased TB prevalence among C/ALHIV, novel TB interventions are likely required to achieve TB elimination and HIV epidemic control in TB/HIV high-burden settings. Funding Statement: This material has been supported by the U.S. President’s Emergency Plan for AIDS Relief through the United States Agency for International Development (USAID) under the terms of USAID Award Number AID-674-A-16-00003. In addition, funds were leveraged from Texas Children’s Hospital to support completion of this research and dissemination of findings. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: No individual participant consent was required for this retrospective analysis of programmatic data. Approval was obtained from all necessary ethical bodies in each country including the Baylor College of Medicine Children’s Foundation or Trust, the national ethics committees in each country, and the Baylor College of Medicine Institutional Review Board.