Adjunctive Dexamethasone Fails to Decrease Mortality for HIV-Positive Adults With Tuberculosis Meningitis

For HIV-positive adults with tuberculosis meningitis, adding dexamethasone to antituberculosis chemotherapy and antiretroviral therapy (ART) did not decrease mortality or any secondary primary outcomes in a double-blind, randomized, placebo-controlled trial.

Tuberculosis meningitis is a serious infection that is common in those with HIV. Although antituberculosis chemotherapy is often used to treat this condition, mortality among this patient population can exceed 50%. Clinicians generally treat HIV-associated tuberculosis meningitis with glucocorticoids, but little is known about its efficacy and safety.

Enter Donovan et al. who conducted a double-blind, randomized, placebo-controlled trial in Vietnam and Indonesia to determine whether dexamethasone would decrease mortality in those with HIV-associated tuberculosis meningitis compared with placebo.

A total of 520 adults with a median age of 36 years treated with antituberculosis chemotherapy and ART were randomly assigned to add either a 6-to-8-week course of tapering dexamethasone (n = 263) or placebo (n = 257) to their treatment. The primary endpoint was any-cause death during 12-months of follow-up, with a secondary endpoint including serious adverse events (SAEs) such as neurologic disability and neurologic immune reconstitution inflammatory syndrome.

During the 12-month follow-up, mortality occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49%) in the placebo group (hazard ratio 0.85; 95% CI, 0.66 to 1.10; p = 0.22).

Researchers found similar percentages of participants with at least one SAE. A total of 192 participants had at least one SAE in the dexamethasone group (73.0%), while 194 of 257 participants had SAEs in the placebo group (75.5%; p = 0.52). Other secondary end-point events were similar between the two groups as well.

This trial had limitations, specifically a small sample size that may have impacted the mortality differences between the two groups.

“In this trial, we did not find a benefit of adjunctive dexamethasone in HIV-positive adults with tuberculous meningitis with respect to survival or any secondary end point over a period of 12 months,” the authors concluded. “The mortality associated with tuberculous meningitis among HIV-positive persons remains unacceptably high, which emphasizes the global importance of enhanced detection and early treatment of HIV and tuberculosis.”

Reference
Donovan J, Bang ND, Imran D, et al. Adjunctive dexamethasone for tuberculous meningitis in hiv-positive adults. N Engl J Med. 2023;389(15):1357-1367. doi:10.1056/NEJMoa2216218.