Systematic, test-guided TB treatment result in similar outcomes

Systematic treatment for tuberculosis was not superior to test-guided treatment in reducing mortality or invasive bacterial disease among immunosuppressed adults with HIV, according to findings in The New England Journal of Medicine.

Systematic treatment was also associated with an increase in grade 3 or 4 adverse events, according to the study results.

“TB is the 10th leading cause of death worldwide and the main cause of death from a single infectious agent. In 2019, WHO estimated that 251,000 annual deaths due to TB occurred in persons with HIV infection,” François-Xavier Blanc, MD, PhD, of the Thorax Institute at Nantes University in France, and colleagues wrote. “Coinfection with TB and HIV still represents a ‘cursed duet,’ especially in sub-Saharan Africa and Asia.”

According to Blanc and colleagues, WHO recommends that people with HIV are systematically screened for active TB and that those with current cough, fever, weight loss or night sweats be examined for TB and other diseases. However, they note that differences in the appearance of chest radiographs and the decrease in the performance of sputum-smear microscopy as CD4+ T-cell count falls can make a TB diagnosis difficult in adults with HIV, particularly when they are severely immunosuppressed.

The researchers performed a 48-week trial of empirical treatment for TB compared with treatment guided by testing in adults with HIV who had not been treated with ART and had CD4+ T-cell counts below 100 cells/mm3. They randomly assigned patients from Ivory Coast, Uganda, Cambodia and Vietnam in a 1:1 ratio to undergo screening to determine if TB treatment should be initiated (525 patients) or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol and pyrazinamide daily for 2 months (522 patients), followed by rifampin and isoniazid daily for 4 months. The primary endpoint was a composite of death from any cause or invasive bacterial disease within 24 weeks in the primary analysis or within 48 weeks after randomization.

At week 24, the rate of death from any cause or invasive bacterial disease was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted HR = 0.95; 95% CI, 0.63-1.44). At week 48, the corresponding rates were 12.8 and 13.3, respectively (aHR = 0.97; 95% CI, 0.67-1.40). The probability of TB was lower at week 24 with systematic treatment than with guided treatment (3% vs. 17.9%; aHR = 0.15; 95% CI, 0.09-0.26), but the likelihood of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; aHR = 2.57; 95% CI, 1.75-3.78). These serious adverse events were more common with systematic treatment.

Both approaches resulted in a lower-than-anticipated rate of death or invasive bacterial disease at week 24, as compared with prior studies.

“... Systematic empirical treatment for TB and treatment guided by specific testing had similar effects on the rate of death or invasive bacterial disease in a population of HIV-infected adults with CD4+ T-cell counts below 100 cells/mm3,” the authors wrote.

In an accompanying commentary, Richard E. Chaisson, MD, professor of epidemiology and international health at Johns Hopkins Bloomberg School of Public Health, wrote that this trial fits into a “suite of studies” about the strategy of empirical anti-TB treatment for patients with established and advanced HIV infection. According to Chaisson, the trial “firmly shuts the door on this intuitive but apparently incorrect concept.”

“For persons with severe immunodeficiency when HIV infection is diagnosed, the best approach may be to promptly start ART and TB preventive therapy and monitor them closely for opportunistic illnesses,” Chaisson wrote. “But it is now clear that empirical antituberculosis therapy for persons with advanced HIV infection is a pound of cure that is worse than an ounce of prevention.”


Source: Healio

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By Caitlyn Stulpin

Published: June 25, 2020, 1:10 p.m.

Last updated: June 30, 2020, 12:15 p.m.

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