A previously healthy 29-year-old man presents with lower extremities weakness, left worse than right, weight loss, and behavioral changes noted in the last year. He unintentionally lost 30 pounds. He noticed increased frequency of urination, feet numbness, and inability to walk. His family reports apathy, isolation, and limited verbal communication. He stopped working. He was cachectic, with diffuse muscle wasting, lower extremities weakness, left foot drop, hyperreflexia, and left Babinski sign. He had hyperpigmented lesions on his back and a penile ulcer. Laboratory testing revealed mild anemia, hypoalbuminemia, elevated inflammatory markers, positive HIV-1Ab, a CD4+ T-cell count of 33 cells/μL, HIV viral load >100,000 copies/mL, RPR+, FTA+, TP-PA+. CT scan of the chest showed bilateral thick-walled irregular cystic structures, ground-glass opacities, and pulmonary nodules, most likely infectious. MRI of the cervical and thoracic spine showed non-enhancing lesions with increased signal at C3, C5-C6, T1-T2, T3-T4, and T5-T6. MRI of the brain revealed non-enhancing hyperintensity in both frontal lobes, corona radiata, posterior limbs of internal capsule, cerebral peduncles, and pons, and hypointense lesions in bilateral precentral gyri. CSF had normal opening pressure, protein, glucose, LDH, and cell count. CSF-PCR was positive for HIV-1 with 44,687 copies/mL, high CSF IgG, and myelin basic protein. The paraneoplastic, autoimmune, demyelination panels, and fluorescent treponemal antibody in CSF were negative.He was diagnosed with HIV-VM with concomitant syphilis infection and treated with IVIG and highly active antiretroviral therapy.