Dexamethasone does not improve tuberculous meningitis survival in HIV

1. In this randomized controlled trial, compared to placebo, dexamethasone did not improve survival in people living with human immunodeficiency virus (PLWH) as well as tuberculous meningitis.

2. The incidence of adverse events and inflammatory syndrome was similar between the dexamethasone and placebo groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Tuberculous meningitis is a serious condition caused by Mycobacterium tuberculosis infection. When occurring in immunocompromised individuals, such as those living with human immunodeficiency virus (HIV), it is associated with high mortality rates. Although glucocorticoids were shown to reduce intracerebral inflammation and improve outcomes in tuberculous meningitis patients, evidence for their benefits in PLWH is lacking. This study was a randomized controlled trial to evaluate the effects of dexamethasone against placebo in HIV-positive adults with tuberculous meningitis in Indonesia and Vietnam, alongside standard antituberculosis chemotherapy. Half of the patients in each group had never received antiretroviral therapy (ART). By 12 months, mortality rates were comparable between the dexamethasone and placebo groups. No subgroups were found to benefit from dexamethasone. Dexamethasone group did not differ from placebo in the incidence of adverse events and immune reconstitution syndrome. These results were generalizable to other resource-poor settings, where access to ART and invasive therapeutic intervention was limited. Overall, no evidence of benefit of adjunctive dexamethasone was demonstrated over placebo in treating HIV-positive adults with tuberculous meningitis.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: The current study was a double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of adjunctive dexamethasone in managing tuberculous meningitis among PLWH. Adult HIV-positive patients in Indonesia and Vietnam diagnosed clinically with tuberculous meningitis treated or planned to be treated with antituberculosis chemotherapy were eligible for inclusion. Exclusion criteria included another suspected brain infection, recent glucocorticoid administration, and antituberculosis chemotherapy for six consecutive days prior to enrollment. Overall, 520 patients were randomized to receive a six-to-eight-week tapering course of dexamethasone or placebo, along with 12 months of antituberculosis chemotherapy. The primary outcome was death from any cause within 12 months after randomization. Secondary outcomes included neurologic disability, neurologic immune reconstitution inflammatory syndrome (IRIS), and new acquired immunodeficiency syndrome (AIDS)-defining event or death. At 12 months, death occurred in 44.1% of patients in the dexamethasone group and 49.0% in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI] 0.66-1.10; p=0.22). No patient subgroups, based on disease severity, diagnostic certainty, drug resistance, or baseline CD4 count, were found to benefit from dexamethasone. The two groups also did not differ in neurologic disability (odds ratio, 1.31; 95%CI, 0.80-2.14), neurologic IRIS (hazard ratio, 1.11; 95%CI, 0.46-2.69), and new AIDS-defining events or deaths (hazard ratio, 0.87; 95%CI 0.68-1.12). The rates of adverse events, including serious adverse events and those resulting in interruption of ART or antituberculosis chemotherapy, were similar across both groups. In summary, these results demonstrated that dexamethasone did not improve mortality and clinical outcomes for PLWH with tuberculous meningitis.

Image: PD

©2023 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.