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Recent Antiretroviral Therapy Initiation Is Associated With Increased Mortality Risk in HIV-associated Cryptococcal
Melanie Moyo1,2, David S Lawrence3,4, James Jafali1
1Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
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.
Insights
Mortality from cryptococcal meningitis is higher in patients recently starting antiretroviral therapy (ART). Interrupting ART shortly after diagnosis may improve survival rates for these human immunodeficiency virus patients.
Area of Science:
- Infectious Diseases
- Immunology
- Public Health
Background:
- Cryptococcal meningitis is a significant concern in human immunodeficiency virus (HIV)-infected individuals.
- Over half of patients with HIV-associated cryptococcal meningitis are already on antiretroviral therapy (ART).
- Optimal management of ART in patients with recent ART initiation (≤14 days) and cryptococcal meningitis remains unclear.
Purpose of the Study:
- To investigate the mortality risk associated with recent ART initiation in cryptococcal meningitis patients.
- To determine the impact of ART interruption on outcomes for patients diagnosed with cryptococcal meningitis shortly after starting ART.
Main Methods:
- Analysis of data from the Ambisome Therapy Induction Optimisation (AMBITION) trial.
- Examination of mortality risk in patients diagnosed with cryptococcal meningitis within 14 days of ART initiation.
- Combined analysis with the Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa trial to assess baseline characteristics based on ART status.
Main Results:
- Patients initiating ART within 14 days of cryptococcal meningitis diagnosis had a 20.8% 2-week mortality risk.
- Mortality risk was lower in patients on ART for longer durations (>2 weeks to 6 months).
- For individuals on ART ≤14 days, discontinuing ART reduced 2-week mortality from 35% to 14% compared to continuing ART.
Conclusions:
- Recent ART initiation is linked to increased mortality in cryptococcal meningitis.
- Interrupting ART in patients with cryptococcal meningitis who recently initiated therapy may improve outcomes.
- Further research is needed to refine ART management strategies in this vulnerable population.
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