Lung cryptococcosis in a treated HIV-1-infected patient with suppressed viral load and past disseminated cryptococcosis: relapse or late IRIS?

Sir, Early initiation of combination antiretroviral therapy (cART) in AIDS presenters reduces mortality, but seems to worsen survival in cryptococcal meningitis, probably because of immune reconstitution inflammatory syndrome (IRIS), with fatal cerebral complications. Timing of cART initiation is not clearly defined, ranging from 2 to 10 weeks. Strategies aiming at reducing the risk of IRIS are lacking. We report a case of pulmonary and mediastinal lymph node cryptococcosis occurring late after immune reconstitution and fluconazole prophylaxis discontinuation in a patient with previous AIDS-presenting disseminated/meningeal cryptococcosis. A Pakistani man in his mid-forties presented with AIDS and disseminated/meningeal cryptococcosis (CD4 count 16 cells/mm, plasma HIV-1 RNA 191100 copies/mL and blood and CSF cultures positive for Cryptococcus neoformans). He was treated with a standard amphotericin B course, followed by secondary fluconazole prophylaxis; cART was introduced 1 month later with co-formulated zidovudine/lamivudine and lopinavir/ritonavir, achieving virological suppression and immune restoration (Figure 1). The nucleoside backbone was switched to tenofovir/emtricitabine after 1 month, because of bone marrow toxicity (haemoglobin 8.3 g/dL, white blood cells 1910/mm and neutrophils 390/mm). Lumbar puncture performed at baseline and after 3 months showed a decrease in HIV-1 RNA in the CSF, although the CSF/plasma viral load ratio did not decrease accordingly (2867/191100 copies/mL1⁄40.02 at baseline versus 123/ 314 copies/mL1⁄40.39 at month 3). In the absence of new clinical symptoms, cryptococcal soluble antigen titre in the CSF increased from 1:512 at baseline to 1:2048 at month 3, but culture was negative; no other neurotropic viruses (herpes viruses 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein–Barr virus or JC virus) were detected by PCR. A viral blip at month 5 (HIV-1 RNA 1170 copies/mL) was not confirmed (HIV-1 RNA ,50 copies/mL after 2 weeks); lopinavir/ ritonavir trough concentrations were adequate (5931 ng/dL/ 306 ng/dL). Fluconazole prophylaxis was stopped after 8 months of cART and CD4 count .200 cells/mm, according to guidelines. Nine months later, the patient presented with cough, malaise, weight loss, anorexia and severe dysphagia. Endoscopy revealed extrinsic oesophageal compression. A whole-body CT scan showed enlargement of mediastinal lymph nodes and bilateral apical pulmonary solid infiltrations. Sputum smears were negative for acid-fast bacilli (even by PCR) and other microbes; T cell