‘LASER-TBM’ Linezolid, ASpirin and Enhanced dose Rifampicin in HIV-TBM

PRIMARY OBJECTIVETo investigate the safety of enhanced antimicrobial therapy including increased dose RIF and LZD with or without adjunctive ASA added to standard therapy for TBM in HIV-1 infected adults.SECONDARY OBJECTIVES1. To determine CSF M.tb culture positivity and Gene Xpert® Ultra positivity at baseline and at 3 and 28 days post treatment by allocation;2. To evaluate the effect of ASA and enhanced TB treatment on the incidence of IRIS in participants starting ART;3. To evaluate the effect of high dose RIF and LZD with and without ASA on the transcriptional signature derived from whole blood and CSF RNA sequencing, as well as the metabolomic and proteomic profiles, in TBM;4. To evaluate the effect of high dose RIF and LZD with and without ASA on CNS imaging in conjunction with clinical, immunological and transcriptional profiling;5. To store biological samples for future analysis of potential biomarkers of treatment efficacy and/or novel diagnostic assays;6. To determine i) whether host genotype, including LTA4H genotype, influences therapeutic effect of ASA in HIV-TBM and ii) pharmacogenetic influence on RIF and LZD exposures and toxicity;7. In a pharmacokinetic (PK) sub-study: Describe the plasma and CSF PK of LZD and high dose RIF, Evaluate the relationship between drug exposures and toxicity and efficacy, Investigate the impact of high dose RIF on LZD and dolutegravir (DTG) exposures, compare exposure between intravenous and oral RIF administration