The Lancet Global Health: Untangling the complex relationship between HIV-exposure and TB in children: A narrative review Children who are HIV-exposed but uninfected (CHEU) face a higher risk of illness and death compared to children with no HIV exposure, despite advances in preventing mother-to-child HIV transmission. This increased vulnerability is especially pronounced for infectious diseases like tuberculosis (TB), which remains a leading cause of death in children globally. With the number of CHEU growing due to successful antiretroviral programs, understanding their heightened susceptibility to TB has develop into a critical focus of global health research. In 2022, there were an estimated 16 million CHEU worldwide, with approximately one million additional children added each year. The majority of these children reside in sub-Saharan Africa, where both HIV and TB burdens are highest. Although effective antiretroviral therapy has dramatically reduced the number of children acquiring HIV through vertical transmission, it has not eliminated the increased health risks faced by those who are exposed to HIV in utero or during birth but remain uninfected. Research indicates that CHEU experience altered immune development, which may impair their ability to control TB infection. These immunological differences, combined with potential socioeconomic and environmental factors, contribute to their increased risk of TB disease progression and worse outcomes following exposure to Mycobacterium tuberculosis. Studies show that CHEU are more likely to develop TB infection and progress to active TB disease than HIV-unexposed children, even when accounting for variables such as malnutrition or crowded living conditions. A narrative review published in The Lancet Global Health by researchers from LMU University Hospital Munich highlights these concerns, emphasizing that even as much is known about the epidemiology of HIV exposure in children, significant gaps remain in understanding the biological mechanisms linking HIV exposure to increased TB susceptibility. The review calls for longitudinal studies to better define the immune profiles of CHEU and to evaluate whether current TB prevention strategies, such as bacille Calmette-Guérin (BCG) vaccination or isoniazid preventive therapy, are sufficient for this population. Experts stress that addressing TB in CHEU requires integrated approaches that combine HIV care platforms with TB screening, preventive therapy, and vaccine research tailored to the unique needs of this group. As the population of CHEU continues to expand, particularly in high-burden settings, targeted interventions are essential to reduce preventable morbidity, and mortality. Ongoing research priorities include identifying biomarkers of TB risk in CHEU, optimizing preventive regimens, and evaluating novel vaccine candidates. Public health programs must also ensure that HIV-exposed infants receive timely follow-up care, including TB exposure assessment and symptom screening, to enable early detection and treatment. The growing population of HIV-exposed but uninfected children represents both a success of global HIV prevention efforts and a new challenge in child health. Ensuring their protection against tuberculosis is not only a medical imperative but a matter of health equity, particularly in regions where HIV and TB epidemics overlap. By investing in targeted research and integrated service delivery, the global health community can improve outcomes for millions of vulnerable children.
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