Persistent Cryptococcal Meningitis Treated with Antiretroviral Therapy and Alternative Antifungals

Because of the relative lack of information surrounding persistent cryptococcal meningitis, treatment presents a clinical dilemma. We report two patients who developed persistent cryptococcal meningitis that was nonresponsive to induction therapy over the course of several weeks. In the first patient, induction therapy with amphotericin and flucytosine was extended. Because of persistently high opening pressures (OPs) and cryptococcal antigen titers at 10 weeks, antiretroviral therapy with the combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was initiated, and the patient’s OP and cryptococcal titers normalized within a week. This patient was well at his 2-week visit but was lost to follow-up after that. In the second patient, induction therapy with amphotericin and flucytosine was continued for 6 weeks due to persistently elevated OPs and cryptococcal antigen titers. At that time, high-dose fluconazole was added. This patient steadily improved and was discharged on fluconazole consolidation therapy. After hospital discharge, this patient was lost to follow-up. Published risk factors for persistent infection that these patients shared were positive human immunodeficiency virus status, elevated cryptococcal antigen titers, and persistently high OP. After initiation of unique, nonstandard therapy of antiretrovirals and high-dose fluconazole, both patients improved. Other potential treatment options for persistent cryptococcal meningitis include voriconazole, posaconazole, interleukin 2, acetazolamide, and the placement of cerebrospinal fluid shunts, but these were not selected because of a variety of relative contraindications or limitations of these agents. With limited data to favor one agent over another, it is important to evaluate case-by-case for treatment decisions.