Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy

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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.Design: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.Setting:Eighty-four French AIDS clinical centres.Patients: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/μl [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 ≥ 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.Conclusion: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.

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