title: Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy.
abstract: BACKGROUND
  Immune restoration following combination antiretroviral therapy (cART) questions the maintenance of prophylaxis among HIV-infected patients with cryptococcosis.
  
  
  OBJECTIVE
  To describe the long-term outcome after the diagnosis of cryptococcosis at the cART era.
  
  
  METHODS
  Multicentre cohort of patients with a diagnosis of cryptococcosis between 1996 and 2000, follow-up until December 2002. Comparison with a historical cohort (1990-1994) for survival.
  
  
  METHODS
  Eighty-four French AIDS clinical centres.
  
  
  METHODS
  Two-hundred and forty HIV-infected adult patients at the cART era and 149 at the pre-cART era experiencing a first episode of culture-confirmed cryptococcosis.
  
  
  RESULTS
  In the cART era, 82/189 patients surviving more than 3 months after initiation of antifungal therapy had their maintenance therapy interrupted with a subsequent median follow-up of 19 months. Their relapse rate per 100 person-years was 0.9 [95% confidence interval (CI),0.0-2.0]. When considering the whole cART cohort, probability of reaching negative serum cryptococcal antigen was 71% after 48 months of follow-up. A CD4 cell count < 100/microl [relative risk (RR), 5.5; 95% CI, 1.3-22.2], antifungal therapy < 3 months over the past 6 months [RR, 5.0; 95% CI, 1.1-22.3] and serum cryptococcal antigen titre > or = 1/512 [RR, 3.5; 95% CI, 1.1-10.8] were associated with a higher rate of cryptococcosis relapse. The mortality rate per 100 person-years was 15.3 [95% CI,12.2-18.4] in the cART era versus 63.8 [95% CI,53.0-74.9] in the pre-cART era although early mortality did not differ between the two periods.
  
  
  CONCLUSIONS
  Overall survival after cryptococcosis has dramatically improved at the cART era. Immune restoration and low serum cryptococcal antigen titres are associated with lower cryptococcosis relapse rates.
authors.affiliation: Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France. olortho@pasteur.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Poizat
authors.forename: Valérie
authors.initials: V
authors.lastname: Zeller
authors.forename: Ségolène
authors.initials: S
authors.lastname: Neuville
authors.forename: André
authors.initials: A
authors.lastname: Boibieux
authors.forename: Muriel
authors.initials: M
authors.lastname: Alvarez
authors.forename: Pierre
authors.initials: P
authors.lastname: Dellamonica
authors.forename: Françoise
authors.initials: F
authors.lastname: Botterel
authors.forename: Françoise
authors.initials: F
authors.lastname: Dromer
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D003453:Cryptococcosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; D015725:Fluconazole