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. 2013 Sep 16;8(9):e74057.
doi: 10.1371/journal.pone.0074057. eCollection 2013.

Duration of anti-tuberculosis therapy and timing of antiretroviral therapy initiation: association with mortality in HIV-related tuberculosis

Claudia P Cortes  1 , Firas H Wehbe, Catherine C McGowan, Bryan E Shepherd, Stephany N Duda, Cathy A Jenkins, Elsa Gonzalez, Gabriela Carriquiry, Mauro Schechter, Denis Padgett, Carina Cesar, Juan Sierra Madero, Jean W Pape, Daniel R Masys, Timothy R Sterling; Caribbean, Central American, South American Network for HIV Research of the International Epidemiologic Databases to Evaluate AIDS
Collaborators, Affiliations

Duration of anti-tuberculosis therapy and timing of antiretroviral therapy initiation: association with mortality in HIV-related tuberculosis

Claudia P Cortes et al. PLoS One. .

Abstract

Background: Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear.

Methods: We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended.

Results: Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm(3), 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007).

Conclusions: The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated.

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Conflict of interest statement

Competing Interests: TRS received research grants from Pfizer, BMS, and Virco. He is a data safety monitoring board member for a study conducted by Otsuka. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

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