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J Acquir Immune Defic Syndr. 2016 Jul 1;72(3):297-303. doi: 10.1097/QAI.0000000000000970.

Empiric TB Treatment of Severely Ill Patients With HIV and Presumed Pulmonary TB Improves Survival.

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*Makerere University-University of California San Francisco (MU-UCSF) Research Collaboration, Kampala, Uganda; †Pulmonary Section, Denver Veteran's Affairs Medical Center, Denver, CO; ‡Department of Biostatistics and Epidemiology, University of California San Francisco, San Francisco, CA; §Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; ‖Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA; ¶Division of HIV/AIDS, Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA; #Department of Epidemiology of Microbial Diseases, School of Public Health, Yale University, New Haven, CT; and **Pulmonary, Critical Care, and Sleep Medicine Section, School of Medicine, Yale University, New Haven, CT.



In 2007, World Health Organization (WHO) issued emergency recommendations on empiric treatment of sputum acid-fast bacillus smear-negative patients with possible tuberculosis (TB) in HIV-prevalent areas, and called for operational research to evaluate their effectiveness. We sought to determine if early, empiric TB treatment of possible TB patients with abnormal chest radiography or severe illness as suggested by the 2007 WHO guidelines, is associated with improved survival.


We prospectively enrolled consecutive HIV-seropositive inpatients at Mulago Hospital in Kampala, Uganda, from 2007 to 2011 with cough for ≥2 weeks. We retrospectively examined the effect of empiric TB treatment before discharge on 8-week survival among those with and without a WHO-defined "danger sign," including fever >39°C, tachycardia >120 beats per minute, or tachypnea >30 breaths per minute. We modeled the interaction between empiric TB treatment and danger signs, and their combined effect on 8-week survival, and adjusted for relevant covariates.


Among 631 sputum smear-negative patients, 322 (51%) had danger signs. Cumulative 8-week survival of patients with danger signs was significantly higher with empiric TB treatment (80%) than without treatment (64%, P < 0.001). After adjusting for duration of cough and concurrent hypoxemia, patients with danger signs who received empiric TB treatment had a 44% reduction in 8-week mortality (risk ratio 0.56, 95% confidence interval: 0.34-0.91, P = 0.020).


Empiric TB treatment of HIV-seropositive, smear-negative, presumed pulmonary TB patients with 1 or more danger signs is associated with improved 8-week survival. Enhanced implementation of the 2007 WHO empiric treatment recommendations should be encouraged whenever and wherever rapid and highly sensitive diagnostic tests for TB are unavailable.

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