|dc.identifier.citation||Blanc, F. X., Badje, A. D., Bonnet, M., Gabillard, D., Messou, E., Muzoora, C., ... & Laureillard, D. (2020). Systematic or test-guided treatment for tuberculosis in HIV-infected adults. New England Journal of Medicine, 382(25), 2397-2410. DOI: 10.1056/NEJMoa1910708||en_US
|dc.description.abstract||In regions with high burdens of tuberculosis and human immunodeficiency virus
(HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are
already severely immunocompromised. Mortality after ART initiation is high in these
patients, and tuberculosis and invasive bacterial diseases are common causes of death.
We conducted a 48-week trial of empirical treatment for tuberculosis as compared
with treatment guided by testing in HIV-infected adults who had not previously
received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter.
Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly
assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan
test, and chest radiography) to determine whether treatment for
tuberculosis should be started or to receive systematic empirical treatment with
rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed
by rifampin and isoniazid daily for 4 months. The primary end point was a composite
of death from any cause or invasive bacterial disease within 24 weeks (primary
analysis) or within 48 weeks after randomization.
A total of 522 patients in the systematic-treatment group and 525 in the guidedtreatment
group were included in the analyses. At week 24, 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 with systematic treatment and 20.3 with guided treatment
(adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48,
the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67
to 1.40]). 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). Serious adverse events were more common with systematic treatment.
Among severely immunosuppressed adults with HIV infection who had not previously
received ART, systematic treatment for tuberculosis was not superior to test-guided
treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks
and was associated with more grade 3 or 4 adverse events. (Funded by the Agence
Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290
ClinicalTrials.gov number, NCT02057796.)||en_US