Management of HIV-associated cryptococcal disease in South Africa

Abstract

In routine-care settings, the 10-week mortality associated with cryptococcal meningitis (CM) is high, even with prompt, appropriate antifungal treatment and correctly timed initiation of antiretroviral therapy (ART). While early diagnosis of HIV infection and initiation of ART prior to the development of AIDS is the most important way to reduce the incidence of CM, a cryptococcal antigenaemia
screen-and-treat intervention has the potential to reduce mortality by identifying patients prior to onset of CM. Antifungal treatment for HIV-associated CM is divided into three phases over a minimum period of 1 year: (i) a 2-week induction phase, including intravenous amphotericin B deoxycholate as a backbone; (ii) an 8-week consolidation phase with fluconazole 400 mg daily; and (iii) a maintenance phase with fluconazole 200 mg daily. Amphotericin B should be paired with another antifungal agent to maximise cerebrospinal fluid fungal clearance. World Health Organization guidelines emphasise that patients receiving amphotericin B-containing regimens should have access to a ‘minimum package of toxicity prevention, monitoring and management to minimise the serious amphotericin B-related toxicities particularly hypokalaemia and nephrotoxicity’. Raised intracranial pressure is a serious and often fatal complication of CM, which requires good pressure management with repeat lumbar punctures. ART should be initiated 4 - 6 weeks after starting antifungal therapy. In many cases, relapse CM among South African patients occurs because of suboptimal adherence to secondary prophylaxis with fluconazole
and/or the antifungal not being prescribed.