One month of rifapentine plus isoniazid to prevent HIV-related Tuberculosis

BRIEF TB/A5279 Study Team

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1001-1011
Number of pages11
JournalNew England Journal of Medicine
Volume380
Issue number11
DOIs
StatePublished - Mar 14 2019

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rifapentine
Isoniazid
Tuberculosis
HIV
Confidence Intervals
Latent Tuberculosis

ASJC Scopus subject areas

  • Medicine(all)

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One month of rifapentine plus isoniazid to prevent HIV-related Tuberculosis. / BRIEF TB/A5279 Study Team.

In: New England Journal of Medicine, Vol. 380, No. 11, 14.03.2019, p. 1001-1011.

Research output: Contribution to journalArticle

BRIEF TB/A5279 Study Team. / One month of rifapentine plus isoniazid to prevent HIV-related Tuberculosis. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 11. pp. 1001-1011.
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abstract = "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.",
author = "{BRIEF TB/A5279 Study Team} and Susan Swindells and Ritesh Ramchandani and Amita Gupta and Benson, {Constance A.} and Jorge Leon-Cruz and Noluthando Mwelase and {Jean Juste}, {Marc A.} and Lama, {Javier R.} and Javier Valencia and Ayotunde Omoz-Oarhe and Khuanchai Supparatpinyo and Gaerolwe Masheto and Lerato Mohapi and {Da Silva Escada}, {Rodrigo O.} and Sajeeda Mawlana and Peter Banda and Patrice Severe and James Hakim and Cecilia Kanyama and Deborah Langat and Laura Moran and Janet Andersen and Fletcher, {Courtney V.} and Eric Nuermberger and Chaisson, {Richard E}",
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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

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

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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