Prognosis and management of cryptococcal meningitis in patients with human immunodeficiency virus infection

Cryptococcal meningitis has emerged as one of the most frequent and deadly opportunistic infections in patients with human immunodeficiency virus (HIV). Cryptococcosis has become the most common cause of adult meningitis in many parts of Africa, where it now rivals tuberculosis in all-cause mortality. While expanding access to antiretroviral therapy in many resource-limited settings has led to improvements in long-term prognosis, early mortality from HIV-associated cryptococcal meningitis remains unacceptably high. Successful management of cryptococcal meningitis is often hindered by unsatisfactory antifungal regimens or by poor control of elevated cerebrospinal fluid pressures. Immune reconstitution inflammatory syndrome also frequently complicates cryptococcal meningitis in patients with acquired immune deficiency syndrome (AIDS) initiating antiretroviral therapy, and the optimal timing of antiretroviral therapy remains unclear. The optimal initial regimen of amphotericin B and flucytosine is difficult to administer and is often not available in resource-limited settings, where cryptococcal meningitis is most prevalent. Fluid and electrolyte coadministration with amphotericin B is essential to minimizing iatrogenic comorbidities. Fortunately, several new approaches have been leading the way toward improving care for cryptococcal meningitis patients in resource-limited settings. Innovative trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different induction regimens. Universal cryptococcal antigen screening of AIDS patients, combined with new point-of-care testing, has the potential to improve the early diagnosis of cryptococcal meningitis markedly in resource-limited settings.