Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published June 17, 2020


How did systematic empirical tuberculosis treatment compare with repeated screening and targeted tuberculosis treatment in the trial by Blanc et al.?

Despite increasing access to antiretroviral therapy (ART) in regions with high burdens of tuberculosis and HIV, many HIV-infected adults still present for care when they are already severely immunocompromised. Among these adults, mortality after the initiation of ART is high, and tuberculosis and invasive bacterial diseases are common causes of death. Blanc et al. conducted a randomized trial to compare the benefits and risks of a strategy involving repeated screening tests — including a combination of 3 tests at initial screening — and targeted tuberculosis treatment with those of a strategy of systematic empirical treatment for tuberculosis in HIV-infected patients with severe immunosuppression. Read the NEJM Original Article here.

Clinical Pearls

Q: How common is tuberculosis worldwide?

A: Tuberculosis is the 10th leading cause of death worldwide and the main cause of death from a single infectious agent. Coinfection with tuberculosis and HIV still represents a “cursed duet,” especially in sub-Saharan Africa and Asia.

Q: What were some of the eligibility criteria for the trial by Blanc et al.?

A: The trial was a multicenter, randomized, open-label, superiority trial that compared the efficacy of two strategies in reducing mortality and the risk of invasive bacterial diseases among ambulatory HIV-infected adults with no overt evidence of tuberculosis, whose CD4+ T-cell count was less than 100 cells per cubic millimeter, and who were ready to start ART.

Morning Report Questions

Q: How did systematic empirical tuberculosis treatment compare with repeated screening and targeted tuberculosis treatment in the trial by Blanc et al.?

A: The results of this trial showed that among severely immunosuppressed adults who had not previously received ART, systematic empirical treatment for tuberculosis was not superior to a strategy involving a combination of repeated tuberculosis screening and targeted treatment for tuberculosis. With respect to the primary outcome, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 in the systematic-treatment group and 20.3 in the guided-treatment group at week 24 (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). 

Q: What were some of the limitations of the trial by Blanc et al.?

A: The authors note several limitations. First, neither of the assigned strategies can be directly compared with those used in current practice. At the time the trial was designed, most clinicians used only sputum smear for tuberculosis screening before initiating ART. Second, although isoniazid preventive therapy was known to decrease the rate of, and mortality from, tuberculosis among HIV-infected adults living in areas with a high burden of tuberculosis, at the time of randomization, isoniazid preventive therapy was deliberately not given to the patients who were assigned to the guided-treatment group to avoid the potential risk of treating undiagnosed tuberculosis with isoniazid alone. Third, despite systematic review, causes of death remained undocumented in 21 patients (23%), particularly among the patients who died in the systematic-treatment group (15 of 45 patients).

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