Background: Tuberculous
meningitis (TBM) is the most severe form of
tuberculosis.
Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether
corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain.
Hepatitis is the most common
drug-induced serious adverse event associated with anti-
tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping
anti-tuberculosis drugs are not evidence-based. This study aims to determine whether
dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-
tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop
drug induced liver injury (DILI) that will enable the safe continuation of
rifampicin and
isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of
dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-
tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in
rifampicin and
isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of
dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether
corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using
corticosteroids in this context is limited. Interruptions in anti-
tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of
rifampicin and
isoniazid therapy.