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ACT HIV

Trial question
What is the role of adjunctive dexamethasone in HIV-positive patients with tuberculous meningitis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
24.0% female
76.0% male
N = 520
520 patients (124 female, 396 male).
Inclusion criteria: HIV-positive patients with tuberculous meningitis.
Key exclusion criteria: brain infection; receipt of antituberculosis chemotherapy for > 6 consecutive days before enrollment; receipt of corticosteroids for > 3 consecutive days before enrollment; systemic corticosteroids considered mandatory or contraindicated.
Interventions
N=263 dexamethasone (tapering course for 6-8 weeks plus 12 months of antituberculosis chemotherapy).
N=257 placebo (tapering course of matching placebo for 6-8 weeks plus 12 months of antituberculosis chemotherapy).
Primary outcome
Death from any cause at 12 months
44.1%
49%
49.0 %
36.8 %
24.5 %
12.3 %
0.0 %
Dexamethasone
Placebo
No significant difference ↔
No significant difference in death from any cause at 12 months (44.1% vs. 49%; HR 0.85, 95% CI 0.66 to 1.1).
Secondary outcomes
No significant difference in neurologic immune reconstitution inflammatory syndrome at 6 months (4.2% vs. 3.5%; HR 1.11, 95% CI 0.46 to 2.69).
No significant difference in neurological disability at 12 months (11.1% vs. 8%; OR 1.31, 95% CI 0.8 to 2.14).
No significant difference in new neurological events or death at 12 months (51% vs. 55.3%; HR 0.85, 95% CI 0.67 to 1.08).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In HIV-positive patients with tuberculous meningitis, dexamethasone was not superior to placebo with respect to death from any cause at 12 months.
Reference
Joseph Donovan, Nguyen D Bang, Darma Imran et al. Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults. N Engl J Med. 2023 Oct 12;389(15):1357-1367.
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