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Tuberculosis Research and Treatment
Volume 2013, Article ID 242604, 7 pages
Clinical Study

Initial Antituberculous Regimen with Better Drug Penetration into Cerebrospinal Fluid Reduces Mortality in HIV Infected Patients with Tuberculous Meningitis: Data from an HIV Observational Cohort Study

Department of Infectious Diseases, Bathalapalli Rural Development Trust Hospital, Kadiri Road, Anantapur District, Bathalapalli 515661, Andhra Pradesh, India

Received 9 June 2013; Revised 18 July 2013; Accepted 18 July 2013

Academic Editor: Luis E Cuevas

Copyright © 2013 Gerardo Alvarez-Uria et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Tuberculous meningitis (TM) is the deadliest form of tuberculosis. Nearly two-thirds of HIV infected patients with TM die, and most deaths occur within one month. Current treatment of TM involves the use of drugs with poor penetration into the cerebro-spinal fluid (CSF). In this study, we present the mortality before and after implementing a new antituberculous regimen (ATR) with a higher drug penetration in CSF than the standard ATR during the initial treatment of TM in an HIV cohort study. The new ATR included levofloxacin, ethionamide, pyrazinamide, and a double dose of rifampicin and isoniazid and was given for a median of 7 days (interquartile range 6–9). The new ATR was associated with an absolute 21.5% (95% confidence interval (CI), 7.3–35.7) reduction in mortality at 12 months. In multivariable analysis, independent factors associated with mortality were the use of the standard ATR versus the new ATR (hazard ratio 2.05; 95% CI, 1.2–3.5), not being on antiretroviral therapy, low CD4 lymphocyte counts, and low serum albumin levels. Our findings suggest that an intensified initial ATR, which likely results in higher concentrations of active drugs in CSF, has a beneficial effect on the survival of HIV-related TM.