Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults

BACKGROUND: Adjunctive corticosteroids are widely used to treat HIV-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a randomized double-blind placebo-controlled trial in HIV-positive adults (≥18 years) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomized to a 6-8 week tapering course of either dexamethasone or placebo in addition to 12 months antituberculosis chemotherapy. The primary endpoint was death from any cause over 12 months from randomization. RESULTS: 520 adults were randomly assigned to receive either dexamethasone (n=263) or placebo (n=257). The median age was 36 years, 255/520 (49.0%) had never received anti-retroviral therapy, and 251/484 (51.9%) had a baseline CD4 count of ≤50 cells/mm(3). Five participants were lost to follow up and 6 withdrew. Over 12 months of follow-up there were 116/263 (44.1%) deaths in the dexamethasone arm and 126/257 (49.0%) deaths in the placebo arm (hazard ratio 0.85, 95% confidence interval 0.66-1.10; P=0.22). Pre-specified analysis did not reveal a sub-group that clearly benefited from dexamethasone. Secondary outcomes occurred with similar frequency across both treatment arms, including the incidence of immune reconstitution inflammatory syndrome. The numbers of participants with at least one serious adverse event were similar between dexamethasone (192/263 [73.0%]) and placebo (194/257 [75.5%]) arms (P=0.52). CONCLUSIONS: We did not establish a benefit of adjunctive dexamethasone in HIV-positive adults with tuberculous meningitis, either on survival or any other secondary endpoint. (Funded by the Wellcome Trust; ClinicalTrials.gov registration NCT03092817.)