Outcomes of Cryptococcal Meningitis in Uganda Before and After the Availability of Highly Active Antiretroviral Therapy

TLDR: Significant CM-associated mortality persists, despite the administration of amphotericin B and HIV therapy, because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation.

Abstract: Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa. Two prospective observational cohorts enrolled human immunodeficiency virus (HIV)-infected antiretroviral-naive persons with CM in Kampala Uganda. The first cohort was enrolled in 2001-2002 (n = 92) prior to the availability of highly active antiretroviral therapy (HAART) and the second was enrolled in 2006-2007 (n = 44) when HAART was available. Ugandans presented with prolonged CM symptoms (median duration 14 days; interquartile range 7-21 days). The 14-day survival rates were 49% in 2001-2002 and 80% in 2006 (P less than .001). HAART was started 35_13 days after CM diagnosis and does not explain the improved 14-day survival rate in 2006. In 2006-2007 the survival rate continued to decrease after hospitalization with only 55% surviving to initiate HAART as an outpatient. Probable cryptococcal-related immune reconstitution inflammatory syndrome occurred in 42% of patients with 4 deaths. At 6 months after CM diagnosis 18 persons (41%) were alive and receiving HAART in 2007. The median cerebral spinal fluid (CSF) opening pressure was 330 mm H2O; 81% of patients had elevated pressure (greater than 200 mm H2O). Only 5 patients consented to therapeutic lumbar puncture. There was a trend for higher mortality for pressures greater than 250 mm H2O (odds ratio [OR] 2.1; 95% confidence interval [CI] 0.9-5.2; P = .09). Initial CSF WBC counts of less than 5 cells/mL were associated with failure of CSF sterilization (OR 17.3; 95% CI 3.1-94.3; P less than .001) and protein levels less than 35 mg/dL were associated with higher mortality (OR 2.0; 95% CI 1.2-3.3; P = .007). Significant CM-associated mortality persists despite the administration of amphotericin B and HIV therapy because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation. Approaches to increase acceptance of therapeutic lumbar punctures are needed. (authors)