A recent study [90] evaluated antifungal combination therapies in the treatment of C. neoformans meningitis in HIV patients. Although significant log reductions in colony forming units were observed with all combinations, substantial numbers of patients remained culture positive 2 weeks after therapy. It may be important to delay ART until CSF sterility can be achieved with effective antifungal combinations such as amphotericin B and flucytosine. However, the exact timing of ART and whether attaining CSF culture sterility is important in avoiding IRIS is unknown. This is illustrated by cases of reactivation cryptococcal meningitis described in four patients who had received at least four weeks of antifungal therapy prior to ART [13, 22, 83] . It is reasonable to administer systemic corticosteroids to alleviate unresponsive inflammatory effects, as anecdotal benefits have been observed in these patients [21, 84] . Furthermore, serial lumbar punctures may be required to manage persistent CSF pressure elevations in these patients [85, 86] . Although continuation of ART has been performed safely [13, 84] , interruption of antiviral therapy may be necessary in severe or unresponsive cases.