Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

• DOI: 10.12688/wellcomeopenres.14006.2
• Publication Date: 2018-06-20T10:05:43Z
• Authors: Joseph Donovan; Nguyen Hoan Phu; Nguyen Thi Hoang Mai; Le Tien Dung; Darma Imran; Erlina Burhan; Lam Hong Bao Ngoc; Nguyen Duc Bang; Do Chau Giang; Dang Thi Minh Ha; Jeremy Day; Le Thi Phuong Thao; Nguyen TT Thuong; Nguyen Nang Vien; Ronald B. Geskus; Marcel Wolbers; Raph L Hamers; Reinout van Crevel; Mugi Nursaya; Kartika Maharani; Tran Tinh Hien; Kevin Baird; Nguyen Huu Lan; Evelyne Kestelyn; Nguyen Van Vinh Chau; Guy E. Thwaites
• Keywords: Alternative medicine; Epidemiology and Pathogenesis of Pneumocystis Pneumonia; Epidemiology; HIV; FOS: Health sciences; Pediatrics; 3. Good health; Treatment; Study Protocol; 03 medical and health sciences; Infectious Diseases; 0302 clinical medicine; Health Sciences; Pathology; Medicine; Tuberculosis; Surgery; Intensive care medicine; Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Diagnosis and Treatment of Spinal Infections; Internal medicine; Rifampicin; Placebo

<ns4:p><ns4:bold>Background: </ns4:bold>Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases risk developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients TBM remains uncertain. Hepatitis common drug-induced serious adverse event associated anti-tuberculosis occurring 20% patients. The suggested concentration thresholds for stopping drugs are not evidence-based. This study aims to determine whether dexamethasone safe effective addition first 6-8 weeks treatment HIV, investigate alternative management strategies subset who develop drug induced liver injury (DILI) that will enable continuation rifampicin isoniazid therapy. </ns4:p><ns4:p><ns4:bold>Methods: </ns4:bold>We perform parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing effect versus placebo on overall standard antiretroviral treatment. trial be set two hospitals Ho Chi Minh City, Vietnam, Jakarta, Indonesia. enrol 520 adults. An ancillary comparison three DILI aim demonstrating which strategy results least interruption identical also performed linked controlled HIV-uninfected adults stratified by LTA4H genotype (LAST ACT). </ns4:p><ns4:p><ns4:bold>Discussion: </ns4:bold>Whether uncertain, current evidence base using this context limited. Interruptions chemotherapy factor death from TBM. Alternative may allow therapy.</ns4:p>