TY - JOUR
T1 - One month of rifapentine plus isoniazid to prevent HIV-related Tuberculosis
AU - BRIEF TB/A5279 Study Team
AU - Swindells, Susan
AU - Ramchandani, Ritesh
AU - Gupta, Amita
AU - Benson, Constance A.
AU - Leon-Cruz, Jorge
AU - Mwelase, Noluthando
AU - Jean Juste, Marc A.
AU - Lama, Javier R.
AU - Valencia, Javier
AU - Omoz-Oarhe, Ayotunde
AU - Supparatpinyo, Khuanchai
AU - Masheto, Gaerolwe
AU - Mohapi, Lerato
AU - Da Silva Escada, Rodrigo O.
AU - Mawlana, Sajeeda
AU - Banda, Peter
AU - Severe, Patrice
AU - Hakim, James
AU - Kanyama, Cecilia
AU - Langat, Deborah
AU - Moran, Laura
AU - Andersen, Janet
AU - Fletcher, Courtney V.
AU - Nuermberger, Eric
AU - Chaisson, Richard E.
N1 - Publisher Copyright:
© 2019 Massachusetts Medical Society.
PY - 2019/3/14
Y1 - 2019/3/14
N2 - BACKGROUND Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates. METHODS We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25. RESULTS A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, −0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P=0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001). CONCLUSIONS A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group.
AB - BACKGROUND Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates. METHODS We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25. RESULTS A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, −0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P=0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001). CONCLUSIONS A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group.
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U2 - 10.1056/NEJMoa1806808
DO - 10.1056/NEJMoa1806808
M3 - Article
C2 - 30865794
AN - SCOPUS:85062854667
SN - 0028-4793
VL - 380
SP - 1001
EP - 1011
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 11
ER -