Discontinuation of Maintenance Therapy for Cryptococcal Meningitis in Patients with AIDS Treated with Highly Active Antiretroviral Therapy: An International Observational Study

Abstract

We conducted a retrospective, multicenter study evaluating the safety of discontinuing maintenance therapy for cryptococcal meningitis after immune reconstitution. Inclusion criteria were a previous definitive diagnosis of cryptococcal meningitis, a CD4 cell count of >100 cells/microL while receiving highly active antiretroviral therapy (HAART), and the subsequent discontinuation of maintenance therapy for cryptococcal meningitis. The primary end point was relapse of cryptococcal disease. As of July 2002, 100 patients were enrolled. When maintenance therapy was discontinued, the median CD4 cell count was 259 cells/microL and the median plasma virus load was <2.30 log10 copies/mL, and serum cryptococcal antigen was undetectable in 56 patients. During a median follow-up period of 28.4 months (range, 6.7-64.5; 262 person-years), 4 events were observed (incidence, 1.53 events per 100 person-years; 95% confidence interval, 0.42-3.92). Three of these patients had a CD4 cell count of >100 cells/microL and a positive serum cryptococcal antigen test result during the recurrent episode. In conclusion, discontinuation of maintenance therapy for cryptococcal meningitis is safe if the CD4 cell count increases to >100 cells/microL while receiving HAART. Recurrent cryptococcal infection should be suspected in patients whose serum cryptococcal antigen test results revert back to positive after discontinuation of maintenance therapy.

The prophylaxis of opportunistic infections in HIV-infected adults

“…This continues lifelong or until sufficient immune reconstitution has taken place. Although international data 14 suggest that prophylaxis in patients on HAART may be discontinued at a CD4 count of 100 cells/L, it might be safer to continue until the CD4 count is above 200 cells/L since no data exist for our patient population. Primary prophylaxis does not form part of any southern African guidelines, but can be considered for selected patients.…”

Prevention of cryptococcosis in HIV‐infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis

“…Several prior studies have shown that it is acceptable to stop cryptococcal suppressive therapy in patients who have a sustained immunological response to HAART [22][23][24]. Therefore, we would expect improved immunological function to result in a decrease in both the prevalence and the incidence of cryptococcosis.…”

Cryptococcosis

“…This has been demonstrated to effectively reduce rates of relapse from ~ 40 % to less than 5 % in the pre-HAART era [78]. Secondary prophylaxis can be discontinued after 1-2 years of antifungal therapy in patients who respond to HAART with rise in CD4 + cell counts to greater than 100 cells/µl and decline in viral load (HIV RNA) to undetectable levels for at least 3 months [62,79,80].…”