title: Determinants of mortality in a combined cohort of 501 patients with HIV-associated Cryptococcal meningitis: implications for improving outcomes.
abstract: BACKGROUND
  Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes.
  
  
  METHODS
  Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality.
  
  
  RESULTS
  Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 × 10(9) cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART).
  
  
  CONCLUSIONS
  CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.
authors: Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
authors: Joseph N
authors: JN
authors: Jarvis
authors: Tihana
authors: T
authors: Bicanic
authors: Angela
authors: A
authors: Loyse
authors: Daniel
authors: D
authors: Namarika
authors: Arthur
authors: A
authors: Jackson
authors: Jesse C
authors: JC
authors: Nussbaum
authors: Nicky
authors: N
authors: Longley
authors: Conrad
authors: C
authors: Muzoora
authors: Jacob
authors: J
authors: Phulusa
authors: Kabanda
authors: K
authors: Taseera
authors: Creto
authors: C
authors: Kanyembe
authors: Douglas
authors: D
authors: Wilson
authors: Mina C
authors: MC
authors: Hosseinipour
authors: Annemarie E
authors: AE
authors: Brouwer
authors: Direk
authors: D
authors: Limmathurotsakul
authors: Nicholas
authors: N
authors: White
authors: Charles
authors: C
authors: van der Horst
authors: Robin
authors: R
authors: Wood
authors: Graeme
authors: G
authors: Meintjes
authors: John
authors: J
authors: Bradley
authors: Shabbar
authors: S
authors: Jaffar
authors: Thomas
authors: T
authors: Harrison
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000401:mortality* / Q000473:pathology*; D000328:Adult; D000349:Africa; D002555:Cerebrospinal Fluid / Q000382:microbiology; D015331:Cohort Studies; D015169:Colony Count, Microbial; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016919:Meningitis, Cryptococcal / Q000401:mortality*; D001523:Mental Disorders / Q000175:diagnosis / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors; D013785:Thailand
keywords: Cryptococcus neoformans; HIV; antiretroviral therapy; cryptococcal meningitis; mortality (determinants)