Recent Antiretroviral Therapy Initiation Is Associated With Increased Mortality Risk in HIV-associated Cryptococcal Meningitis: An Analysis of Clinical Trial Data From Africa

Background More than half of people diagnosed with human immunodeficiency virus-associated cryptococcal meningitis are antiretroviral therapy (ART)-experienced. The impact of recent ART initiation (≤14 days) on outcomes from cryptococcal meningitis, and how to optimally manage ART in this patient population, are unknown. Methods We analyzed data from the recent Ambisome Therapy Induction Optimisation (AMBITION) trial to (1) examine whether patients diagnosed with cryptococcal meningitis within 14 days of ART initiation are at higher risk of mortality and (2) determine the impact of ART interruption at diagnosis of cryptococcal meningitis. Combined data from the AMBITION trial and the earlier Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa trial were analyzed to describe baseline characteristics of patients according to ART status. Results Among the 810 AMBITION participants, adjusted 2-week mortality risk was 20.8% (95% confidence interval [CI]: 11.5-30.2; 26/120) in those on ART for 14 days or less at presentation, 10.4% (95% CI: 3.6-17.2; 18/130) on ART for >2 weeks to 2 months, 7.1% (95% CI: 0-14.9; 7/92) on ART for >2 months to 6 months, and 13.0% (95% CI: 8.5-17.6; 50/307) in those on ART for more than 6 months compared to 12.4% (95% CI: 9.2-15.5; 111/707) among individuals not on ART. In the combined dataset, baseline fungal burdens were lower and baseline CD4 counts were higher with increasing ART duration. Among individuals on ART for ≤14 days at presentation, 2-week mortality was 35% (8/23) in those continuing ART versus 14% (7/49) in those discontinuing ART. Conclusions Mortality from cryptococcal meningitis was higher in recent ART initiators. ART interruption in this group may lead to improved outcomes.