Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: The role of inadequate secondary prophylaxis

Objectives. Cryptococcal meningitis is the most common cause of adult meningitis in southern Africa. Much of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We studied the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal meningitis. Design. A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town. Outcome measures. Relapse episodes were categorised into: (i) patients not taking fluconazole prophylaxis; (ii) immune reconstitution inflammatory syndrome (IRIS); and (iii) relapses occurring prior to ART in patients taking fluconazole. In-hospital mortality was recorded. Results. There were 69 relapse episodes, accounting for 23% of all cases of cryptococcal meningitis; 43% (N=30) of relapse episodes were in patients not receiving fluconazole prophylaxis, 45% (N=31) were due to IRIS, and 12% (N=8) were in patients pre-ART taking fluconazole. Patients developing relapse due to inadequate secondary prophylaxis had severe disease and high in-hospital mortality (33%). Of the 30 patients not taking fluconazole, 47% (N=14) had not been prescribed secondary prophylaxis by their health care providers. We documented no relapses due to fluconazole resistance in these patients who received amphotericin B as initial therapy. Conclusions. A large number of relapses of cryptococcal meningitis are due to failed prescription, dispensing and referral for or adherence to secondary fluconazole prophylaxis. Interventions to improve the use of secondary fluconazole prophylaxis are essential.