1. Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status
- Author
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Tweed, Conor D, Crook, Angela M, Dawson, Rodney, Diacon, Andreas H, McHugh, Timothy D, Mendel, Carl M, Meredith, Sarah K, Mohapi, Lerato, Murphy, Michael E, Nunn, Andrew J, Phillips, Patrick PJ, Singh, Kasha P, Spigelman, Melvin, and Gillespie, Stephen H
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Infectious Diseases ,Sexually Transmitted Infections ,Tuberculosis ,Patient Safety ,Emerging Infectious Diseases ,HIV/AIDS ,Rare Diseases ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Antitubercular Agents ,Ethambutol ,Female ,HIV Seropositivity ,Humans ,Incidence ,Isoniazid ,Linear Models ,Male ,Multivariate Analysis ,Prospective Studies ,Pyrazinamide ,Rifampin ,Risk Factors ,Treatment Outcome ,Tuberculosis ,Pulmonary ,United Kingdom ,Clinical trials ,HIV ,Adverse events ,Cardiorespiratory Medicine and Haematology ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
BackgroundThe phase III REMoxTB study prospectively enrolled HIV-positive (with CD4+ count > 250 cells, not on anti-retroviral therapy) and HIV-negative patients. We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial.MethodsForty-two HIV-positive cases were matched to 220 HIV-negative controls by age, gender, ethnicity, and trial site using coarsened exact matching. Grade 3 and 4 adverse events (AEs) were summarised by MedDRA System Organ Class. Kaplan-Meier curves for time to first grade 3 or 4 AE were constructed according to HIV status with hazard ratios calculated. Patients were considered cured if they were culture negative 18 months after commencing therapy with ≥2 consecutive negative culture results.ResultsTwenty of 42 (47.6%) HIV-positive and 34 of 220 (15.5%) HIV-negative patients experienced ≥1 grade 3 or 4 AE, respectively. The majority of these were hepatobiliary disorders that accounted for 12 of 40 (30.0%) events occurring in 6 of 42 (14.3%) HIV-positive patients and for 15 of 60 (25.0%) events occurring in 9 of 220 (4.1%) HIV-negative patients. The median time to first grade 3 or 4 AE was 54 days (IQR 15.5-59.0) for HIV-positive and 29.5 days (IQR 9.0-119.0) for HIV-negative patients, respectively. The hazard ratio for experiencing a grade 3 or 4 AE among HIV-positive patients was 3.25 (95% CI 1.87-5.66, p
- Published
- 2019