Background: Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating central nervous system disorder caused by JC virus reactivation in immunocompromised individuals, particularly those with advanced HIV. Although rare, its occurrence alongside pulmonary tuberculosis (TB) poses significant diagnostic and therapeutic challenges. Case Presentation: We report the case of a 34-year-old male who presented with prolonged fever, Productive cough, significant weight loss, and progressive neurological decline. He was diagnosed with advanced HIV infection (CD4 count: 95 cells/μL) and pulmonary TB, confirmed by sputum CBNAAT. Neuroimaging revealed lesions suggestive of PML, later confirmed by cerebrospinal fluid analysis detecting JC virus DNA. The patient was initiated on antitubercular therapy, followed by antiretroviral therapy after stabilization. Systemic improvements included increased appetite and weight gain of 8kg; however, neurological recovery remained limited. Conclusion: This case underscores the complexity of managing advanced HIV with concurrent opportunistic infections like PML and TB. Early diagnosis using advanced imaging and molecular diagnostics, along with multidisciplinary management strategies, is critical for optimizing outcomes. However, neurological prognosis in PML remains poor, highlighting the need for innovative therapeutic approaches targeting JC virus and enhancing myelin repair.
On behalf of all authors, the corresponding author states that there is no conflict of interest.

Keywords:Progressive Multifocal Leukoencephalopathy; JC virus; HIV/AIDS; Opportunistic infections; Antiretroviral therapy; Immune reconstitution