Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy.
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.
Lortholary
Olivier
O
Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France. olortho@pasteur.fr
Poizat
Gwendoline
G
Zeller
Valérie
V
Neuville
Ségolène
S
Boibieux
André
A
Alvarez
Muriel
M
Dellamonica
Pierre
P
Botterel
Françoise
F
Dromer
Françoise
F
Chêne
Geneviève
G
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
D000935:Antifungal Agents; D000946:Antigens, Fungal; D015725:Fluconazole