Clinical Trials Registration
toxicity, human immunodeficiency virus, TBM, HIV coinfection
HUMAN IMMUNODEFICIENCY VIRUS, HIV COINFECTION, TUBERCULOUS MENINGITIS, TUBERCULOUS MENINGITIS, TUBERCULOSIS (TB)
NCT03927313.In this phase 2A, randomized, controlled trial, we demonstrate that high-dose rifampicin and adjunctive linezolid is safe in adult human immunodeficiency virus–associated tuberculous meningitis. Larger studies are required to evaluate potential toxicity with high-dose aspirin in relation to benefit on morbidity and mortality.Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). With currently available treatment, mortality is high, up to 50% in those coinfected with human immunodeficiency virus (HIV) [Rifampicin at standard adult doses seldom achieves adequate cerebrospinal fluid (CSF) concentrations [A number of clinical trials are investigating either the PK properties of linezolid (NCT04021121, NCT03537495) or efficacy of high-dose rifampicin (ISRCTN15668391) as single adjunctive therapies in TBM, and 1 phase 3 trial is evaluating the efficacy of linezolid, high-dose rifampicin, and lower-dose aspirin (NCT04145258). However, safety data on the use of rifampicin and linezolid in combination, of high-dose aspirin in combination with intensified antibiotics, and in the context of HIV coinfection are absent. LASER-TBM (Linezolid, Aspirin and Enhanced Dose Rifampicin in HIV-TBM) aimed to generate much-needed safety data on the use of enhanced antimicrobial therapy including higher-dose rifampicin (35 mg/kg) and linezolid (1200 mg reducing to 600 mg daily) with or without adjunctive high-dose aspirin (1000 mg daily) in HIV-associated TBM to inform their use in definitive clinical trials.