Journal Article

Treatment of Active Tuberculosis in HIV-Coinfected Patients: A Systematic Review and Meta-Analysis

Faiz A. Khan, Jessica Minion, Madhukar Pai, Sarah Royce, William Burman, Anthony D. Harries and Dick Menzies

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 9, pages 1288-1299
Published in print May 2010 | ISSN: 1058-4838
Published online May 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/651686
Treatment of Active Tuberculosis in HIV-Coinfected Patients: A Systematic Review and Meta-Analysis

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Background. Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse.

Methods. A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutincontaining regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta-regression was performed using negative binomial regression.

Results. After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1–11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase ( patients from 35 study arms), n = 3352 thrice-weekly therapy (n = 211 patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5–10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8–12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with ⩾8 months, or if antiretroviral therapy was not used.

Conclusions. This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.

Journal Article.  5600 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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