A 28-year-old male with a history of HIV/AIDS and cryptococcal meningitis is admitted for management of severe, persistent headache. The headache is bilateral and throbbing, similar to previous episodes secondary to flares of cryptococcal meningitis. He reports Excedrin provides him with one hour of relief. Additionally, he reports neck rigidity and photophobia. He was started on Biktarvy five months ago. At presentation, his CD4 count is 88. Lumbar puncture (LP) showed opening pressure of 32mmHg and cerebral spinal fluid (CSF) showed pleocytosis, elevated protein, with positive cryptococcal antigen. His existing fluconazole consolidation therapy was increased to 800mg daily.

For pain control, serial LPs were performed with persistently high opening pressure. Initial pain medication regimen consisted of IV Dilaudid 1mg q4h, PO Oxycodone 5mg q6h, and Ibuprofen 800mg q6h. Two weeks into hospitalization, the patient was determined to fit criteria for C-IRIS due to persistent pleocytosis and elevated protein in the CSF despite active antifungal treatment. Prednisone was started. The patient reported slight improvement in mental status and headache but complained of not tolerating PO oxycodone well due to nausea. The regimen was subsequently switched to IV Dilaudid 0.5mg q6h, PO Dilaudid 2mg q4h, with unchanged Ibuprofen. Overnight, the patient become agitated, complaining of severe pain and reporting that PO Dilaudid provided no relief and requested more IV medication. After careful and thorough patient education about IV opiate tapering in anticipation of transition to outpatient care, a compromise was reached. The IV Dilaudid dose was kept at 0.5mg but with frequency increased to q4h. Lidocaine patches were also applied to the patient’s neck and back. The patient reported improved pain control in following days and tolerated spacing out IV Dilaudid back to q6h. The patient then reported wanting to go back on PO oxycodone instead of PO Dilaudid due to tolerance concerns. The patient responded well to prednisone, with serial LPs showing normalization of opening pressure and cell counts. On hospital day 39, patient demonstrated appropriate mental status and good pain control. He was subsequently discharged with PO Oxycodone 7.5mg- Acetaminophen 325mg q8h among other medications and instructed to follow up in clinic in one week.

C-IRIS refers to a set of inflammatory conditions that result in paradoxical worsening of cryptococcal infection weeks to months after initiation of HIV therapy. It can occur in over 10% of HIV patients and carries significant risk for mortality. In addition to prednisone therapy, patients often require extensive pain management due to exacerbation of meningitis symptoms. While patients may initially require high doses of IV opiates, discharge planning and PO pain medication transition should be planned from hospital day one. This challenging process often involves comprehensive patient education, sincere compromises, and shared decision making.