Empirical Tuberculosis Treatment in Human Immunodeficiency Virus (HIV)-Associated Fever of Unknown Origin: A Case-Based Rationale

Fever of unknown origin (FUO) in people living with human immunodeficiency virus (PLHIV) is clinically defined as recurrent fever lasting more than four weeks in the outpatient setting or more than three days during hospitalization, despite a thorough diagnostic evaluation. This evaluation typically includes a comprehensive medical history, physical examination, imaging studies (such as chest radiography), and an extensive range of laboratory tests, including complete blood counts, blood and urine cultures, and metabolic panels. Among the many possible causes, tuberculosis (TB) stands out as a leading concern, given its disproportionate burden in PLHIV. However, whether to initiate empirical anti-tubercular therapy in HIV-positive patients presenting with FUO remains a matter of clinical debate. The variability in regional TB prevalence and resource availability makes universal recommendations difficult to apply. In this context, we review the available evidence supporting the use of empirical TB treatment in PLHIV with FUO, aiming to guide clinical decision-making in settings where diagnostic certainty is elusive.