In February 2021 (day 0), a 56-year-old Ugandan woman presented to the Infectious Disease Unit of Kiruddu National Referral Hospital, Uganda, with a two-month history of mild-to-moderate, on-and-off headaches, which were worse in the mornings and were associated with neck pain, nausea, and blurred vision. She denied any history of convulsions, fever, vomiting, photophobia, diplopia, altered level of consciousness or impaired hearing.
Her past medical history is significant for HIV-1 infection diagnosed in 2006 for which she was commenced on Zidovudine (AZT), Lamivudine (3TC) and Efavirenz (EFV) as first-line antiretroviral therapy. She was also diagnosed with systemic arterial hypertension in 2014, managed with bendroflumethiazide (5 mg once daily). She reported good adherence to antiretroviral therapy as well as her antihypertensive medication.
Her initial antiretroviral therapy regimen (AZT/3TC/EFV) was programmatically switched to Tenofovir Disoproxil Fumarate (TDF), 3TC, and Dolutegravir (DTG) regimen and her cotrimoxazole (CTX) prophylaxis discontinued in May 2019 since she had undetectable HIV RNA viral load and her CD4+ T-cell count at the time was 767 cells per microliter. In January 2020 (day -364), she was diagnosed with asymptomatic cryptococcal antigenemia (she had a positive serum CrAg and a negative cerebrospinal fluid CrAg). She completed 24 weeks of fluconazole and was well and asymptomatic. Eight months prior to admission (day -224), she received isoniazid as tuberculosis preventive therapy.
On admission (day 0), her vitals were as follows: axillary temperature - 36.0 C, pulse rate - 83 beats per minute, blood pressure - 130/74mmHg and respiratory rate - 14 breaths per minute. On further physical exam, she was in fair general condition, conscious and alert, and fully oriented in person, place and time.
Neurological exam revealed a Glasgow coma scale of 15/15, no obvious craniopathies, her neck was stiff. However, both Kernig's and Brudzinski's signs were negative. Muscle tone, bulk, tendon reflexes, and sensation were normal. Other systemic examination was unremarkable.
On day 0, both serum and cerebrospinal fluid CrAg lateral flow assay tests (IMMY, Oklahoma, USA) were negative, despite serial dilutions. CD4+ T-cell count was 766 cells/microliter and HIV RNA viral load was undetectable abdominal ultrasound and chest x-ray were normal and the Urine lipoarabinomannan lateral flow assay was negative. Given the high index of suspicion, a lumbar puncture was ordered and results are as shown in Table 1.  
Her admission hemoglobin was 12.8g/dL, platelet 219 x10^3/microL and white cell count of 5.5 x10^3/microL with normal differentials. The rest of the full hemogram parameters were normal. Baseline renal and liver biochemistries were within normal limits.
India ink preparation and quantitative cultures on Sabouraud agar were suggestive of Cryptococcus spp, (Figure 1) supporting the diagnosis of cryptococcal meningitis.
On day 1, she was commenced on intravenous amphotericin B deoxycholate (1mg/kg) for 3 days (considering 10 CFU growth of Cryptococcus spp) in combination with oral flucytosine (100mg/kg) for 7 days and then fluconazole 1200mg once daily for the next 11 days.
By day 7, she was symptom free and quantitative cerebrospinal fluid culture was negative for Cryptococcus spp. She was discharged on day 9. At 10 weeks (day +40) and 18 weeks (day +72), she was well and adherent to her antiretroviral therapy and on maintenance phase of cryptococcal meningitis on fluconazole at a dose of 400mg once daily.