One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis
Susan Swindells, Ritesh Ramchandani, Amita Gupta, Constance A Benson, Jorge Leon-Cruz, Noluthando Mwelase, Marc A Jean Juste, Javier R Lama, Javier Valencia, Ayotunde Omoz-Oarhe, Khuanchai Supparatpinyo, Gaerolwe Masheto, Lerato Mohapi, Rodrigo O da Silva Escada, Sajeeda Mawlana, Peter Banda, Patrice Severe, James Hakim, Cecilia Kanyama, Deborah Langat, Laura Moran, Janet Andersen, Courtney V Fletcher, Eric Nuermberger, Richard E Chaisson, BRIEF TB/A5279 Study Team, Sharlaa Badal-Faesen, Mohammed Rassool, Patricia Segura, Fanny Rosas, Carmela Ganoza, Jessica Rios, Unoda Chakalisa, Mpho S Raesi, Lesedi Tirelo, Moakanyi Ramogodiri, Lerato Mohapi, Debra Peters, Lidiane de Oliveira Tuler, Jessica Calazans, Patcharaphan Sugandhavesa, Nantisa Chotirosniramit, Sajeeda Mawlana, Rejoice Mosia, Felluna Chauwa, Godwin Ulaya, Patrice Sévère, Sandy Nérette, James Hakim, Cecilia Kanyama, Charity Potani, Deborah Langat, Josphat Kosgei, Agnes M Nzioka, Priscilla C Cheruiyot, Elisha Okeyo, Prisca Rabuogi, Luiz Felipe de Souza Moreira, Ivete Martins Gomesc, Breno Riegel Santos, Rita de Cassia Alves Lira, Kiat Ruxrungtham, Anchalee Avihingsanon, Roger Bedimo, Jennifer Klein, Fred R Sattler, Frances Canchola, Cathi Basler, Graham Ray, Roberto C Arduino, Aristoteles E Villamil, Jerrold Ellner, Betsy Adams, David L Cohn, Christie Lynn Costanza, Shazia Chatha, Stephen A Spector, Lisa Stangl, Annie Luetkemeyer, Jay Dwyer, Margaret A Fischl, Hector Bolivar, Nina Lambert, Johnny Perez, Michael Yin, Magdalena Sobieszczyk, Shelia Dunaway, Sheryl Storey, Susan Pedersen, Jonathan Oakes, Jason E Stout, Jacquelin Granholm, Norman Markowitz, Linda Makohon, John Baxter, Pola De La Torre, Rodrigo Carvalho Santana, Marisa M Mussi-Pinhata, Ruben Lopez, Eric Daar, Jill Kunkel, DeeDee Pacheco, Susan Swindells, Ritesh Ramchandani, Amita Gupta, Constance A Benson, Jorge Leon-Cruz, Noluthando Mwelase, Marc A Jean Juste, Javier R Lama, Javier Valencia, Ayotunde Omoz-Oarhe, Khuanchai Supparatpinyo, Gaerolwe Masheto, Lerato Mohapi, Rodrigo O da Silva Escada, Sajeeda Mawlana, Peter Banda, Patrice Severe, James Hakim, Cecilia Kanyama, Deborah Langat, Laura Moran, Janet Andersen, Courtney V Fletcher, Eric Nuermberger, Richard E Chaisson, BRIEF TB/A5279 Study Team, Sharlaa Badal-Faesen, Mohammed Rassool, Patricia Segura, Fanny Rosas, Carmela Ganoza, Jessica Rios, Unoda Chakalisa, Mpho S Raesi, Lesedi Tirelo, Moakanyi Ramogodiri, Lerato Mohapi, Debra Peters, Lidiane de Oliveira Tuler, Jessica Calazans, Patcharaphan Sugandhavesa, Nantisa Chotirosniramit, Sajeeda Mawlana, Rejoice Mosia, Felluna Chauwa, Godwin Ulaya, Patrice Sévère, Sandy Nérette, James Hakim, Cecilia Kanyama, Charity Potani, Deborah Langat, Josphat Kosgei, Agnes M Nzioka, Priscilla C Cheruiyot, Elisha Okeyo, Prisca Rabuogi, Luiz Felipe de Souza Moreira, Ivete Martins Gomesc, Breno Riegel Santos, Rita de Cassia Alves Lira, Kiat Ruxrungtham, Anchalee Avihingsanon, Roger Bedimo, Jennifer Klein, Fred R Sattler, Frances Canchola, Cathi Basler, Graham Ray, Roberto C Arduino, Aristoteles E Villamil, Jerrold Ellner, Betsy Adams, David L Cohn, Christie Lynn Costanza, Shazia Chatha, Stephen A Spector, Lisa Stangl, Annie Luetkemeyer, Jay Dwyer, Margaret A Fischl, Hector Bolivar, Nina Lambert, Johnny Perez, Michael Yin, Magdalena Sobieszczyk, Shelia Dunaway, Sheryl Storey, Susan Pedersen, Jonathan Oakes, Jason E Stout, Jacquelin Granholm, Norman Markowitz, Linda Makohon, John Baxter, Pola De La Torre, Rodrigo Carvalho Santana, Marisa M Mussi-Pinhata, Ruben Lopez, Eric Daar, Jill Kunkel, DeeDee Pacheco
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. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).
Copyright © 2019 Massachusetts Medical Society.
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Source: PubMed