Timing of Art in Cryptococcal Disease
The exact timing of ART initiation in patients with cryptococcosis and HIV coinfection is yet to be determined. In patients with opportunistic infections such as Pneumocystis jiroveci, delayed initiation of ART is associated with higher rates of AIDS progression and/or death than early initiation of ART. Early initiation of ART in patients with tuberculosis is associated with increased risk of IRIS, but decreased mortality, particularly in those with low CD4 counts. In patients with tuberculous meningitis, early ART initiation is not associated with improved clinical outcomes. Early initiation of ART in patients with cryptococcal meningitis is associated with poor clinical outcomes. In a study conducted in Zimbabwe, patients were randomized to early initiation of ART (within 72 h of diagnosis) or delayed initiation (at 10 wk). Patients who were initiated on ART early had significantly higher 3-year mortality than those in whom ART was delayed (88% vs. 54%, p = 0.006). All patients were treated with fluconazole monotherapy at 800 mg once daily. Early ART was also associated with increased mortality in Ugandan patients with cryptococcal meningitis treated with amphotericin B therapy who were randomized to early ART initiation within 1 to 2 weeks of starting antifungal therapy compared with those in whom ART was delayed and initiated at 5 to 6 weeks (D Bouleware, CROI 2013). Most experts would recommend delaying initiation of ART in patients with cryptococcal meningitis and HIV infection for at least 4 weeks, particularly in patients who are treated with fluconazole monotherapy.