Duration of Anti-Tuberculosis Therapy and Timing of Antiretroviral Therapy Initiation: Association with Mortality in HIV-Related Tuberculosis

Claudia P Cortes,Firas H Wehbe,Catherine C Mcgowan,Gabriela Carriquiry,Elsa Gonzalez,Juan Sierra Madero,Bryan E Shepherd,Timothy R Sterling,Carina Cesar,Daniel R Masys,Jean W Pape,Stephany N Duda,Cathy A Jenkins,Mauro Schechter,Denis Padgett,Sean Emery

doi:10.1371/journal.pone.0074057

Abstract

BackgroundAntiretroviral 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.MethodsWe 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.ResultsOf 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 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).ConclusionsThe 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.

Highlights

According to 2010 World Health Organization estimates, 1.7 million people in Latin America and the Caribbean are living with HIV/AIDS
Persons diagnosed with tuberculosis were younger, more likely to be from Peru, have heterosexual sex as their HIV risk factor, have lower CD4+ lymphocyte count and higher HIV-1 RNA at Antiretroviral therapy (ART) initiation, and more likely to die than persons not diagnosed with tuberculosis
In univariate Cox proportional hazards models of time from tuberculosis diagnosis to death among all tuberculosis patients, being diagnosed with tuberculosis after ART initiation tended to be associated with an increased risk of death compared to persons diagnosed with tuberculosis before ART initiation (Table 3)

Summary

Introduction

According to 2010 World Health Organization estimates, 1.7 million people in Latin America and the Caribbean are living with HIV/AIDS. Among HIV-infected persons who develop tuberculosis after initiating ART, persons diagnosed with tuberculosis in the first 3 months of ART may have an increased risk of death compared to those who develop tuberculosis later [8,9]. 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. 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). 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

Methods

Results

Conclusion