Steroids flop in HIV patients with tubercular meningitis: NEJM

Tuberculous meningitis is a serious complication caused by Mycobacterium tuberculosis. World Health Organization (WHO) estimates 10.4 million new TB cases each year of which 1 million are children, reports suggest that at least 100,000 individuals develop TBM develop annually, but this figure may be much higher.

Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV) associated tuberculous meningitis despite limited data supporting their safety and efficacy. A recent study in New England Journal of Medicine evaluated safety and efficacy of the same in HIV patients.

The double blinded randomized trial found that there was no beneficial results in HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not show much difference in survival or any secondary end point.

Researchers conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization.

The key findings of the study are

• A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants).

• The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less.

• Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P=0.22).

• Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups.

• The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P=0.52).

Researchers concluded that “Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point”.

Reference: Donovan J, et al "Adjunctive dexamethasone for tuberculous meningitis in HIV-positive adults" N Engl J Med 2023; DOI: 10.1056/NEJMoa2216218.