Intersecting Epidemics: Immune Dysregulation Associated with HIV and Tuberculosis Syndemic contribute to Increased risk of hypertensive disease in Sub-Saharan Africa

Pheletso Letuka^1,2Michael Z. Zulu^2,3*

• ¹Division of Cardiology, Cape Heart Institute, University of Cape Town, Cape Town, South Africa
• ²SAMRC Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, University of Cape Town, Cape Town, South Africa
• ³Department of Virology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa

Hypertension (HTN) is a chronic medical condition characterized by systolic blood pressure of ≥ 140 mmHg and diastolic blood pressure > 80 mmHg upon repeated measurements. It is one of the most common non-communicable diseases affecting 30% of the global population. Sub-Saharan Africa (SSA) has a high burden of infectious diseases, which contribute to the increased prevalence of hypertension. Furthermore, SSA has the highest number of people living with chronic infectious diseases, such as human immunodeficiency virus (HIV) and tuberculosis (TB). The pathogenesis of these conditions is associated with chronic, low-grade inflammation and immune activation that complicates various homeostatic functions, leading to increased risk of non-communicable diseases among this population. Furthermore, persistent immune activation leads to endothelial dysfunction, arterial stiffness, and altered vascular tone, which contribute to elevated and treatment-refractory blood pressure. However, immunological factors that contribute to the development and pathogenesis of hypertension remain poorly understood. Antiretroviral therapy and anti-TB medications further complicate this landscape by inducing metabolic disturbances and modulating drug metabolism, which affects the efficacy of anti-hypertensive medications. There is a paucity of data and studies reporting on immune dysregulation associated with HTN amongst people living with chronic infections such as HIV and TB. This review aims to highlight this gap in knowledge and the need for more translational research studies to improve health outcomes in hypertensive individuals living with HIV and TB in SSA. Understanding these intertwined immunological and pathophysiological mechanisms is crucial to developing targeted interventions for managing HTN, especially in this vulnerable population.