Abstract Background Advanced HIV infection remains a major risk factor for opportunistic infections despite the availability of effective antiretroviral therapy (ART). Cytomegalovirus (CMV) viremia and JC virus-associated progressive multifocal leukoencephalopathy (PML) are well-recognized complications of severe immunosuppression, but their simultaneous occurrence is exceedingly rare and often fatal. Recognition of this overlap is crucial for timely diagnosis and multidisciplinary management. Case A 34-year-old man with advanced HIV and prolonged ART nonadherence (∼3 years) presented with progressive weakness, weight loss, cough, and dyspnea. He was febrile, tachycardic, and hypoxic (SpO288%). Initial labs showed hemoglobin 9.8 g/dL, platelets 448 K, and LDH 329 U/L. Chest CT revealed bilateral centrilobular nodularity and consolidation, while head CT showed vasogenic edema. Brain MRI demonstrated bilateral basal ganglia and white-matter T2 hyperintensities without enhancement or diffusion restriction. Repeat MRI revealed marked progression with confluent, non-enhancing T2 hyperintensities involving the deep and frontal subcortical white matter, basal ganglia, thalami, midbrain, splenium of the corpus callosum, cerebellar dentate nuclei, and temporal lobes. CSF analysis showed 10 WBC/µL (lymphocytic) with a negative meningitis/encephalitis panel. Bronchoalveolar lavage grew Candida glabrata and Candida albicans; PJP PCR was negative. JC virus DNA was detected, and CMV viremia measured 46,744 IU/mL.He was treated with ART, broad-spectrum antimicrobials, antifungal therapy, and COVID-19-directed management. Despite aggressive therapy, his neurological status declined, and he was transitioned to comfort care Discussion This case illustrates the rare coexistence of CMV viremia and JC virus-associated PML in advanced HIV with multisystem opportunistic infections. Rapid radiologic progression highlighted the diffuse CNS involvement typical of PML. Diagnostic and therapeutic challenges stemmed from overlapping infections, evolving immune status, and the potential for immune reconstitution inflammatory syndrome (IRIS) after ART initiation. Despite prompt recognition and treatment, the outcome remained poor, underscoring the devastating course of PML in the setting of advanced AIDS. Conclusion This case underscores the need for heightened vigilance for concurrent opportunistic infections in patients with poor ART adherence. Comprehensive early diagnostic evaluation, timely ART reinitiation, and sustained adherence support remain essential to preventing catastrophic outcomes from multifocal opportunistic disease. Keywords: AIDS; HIV nonadherence; CMV viremia; JC virus; PML; fungal pulmonary infection; multisystem opportunistic infection This abstract is funded by: none
Ashfaq et al. (Fri,) studied this question.