Gavin Churchyard1, Vicky Cárdenas2, Violet Chihota3, Kathy Mngadi2, Modulakgotla Sebe2, William Brumskine2, Neil Martinson4, Getnet Yimer5, Shu-Hua Wang5, Alberto L Garcia-Basteiro6, Dinis Nguenha6, LeeAnne Masilela2, Zainab Waggie2, Susan van den Hof7, Salome Charalambous3, Frank Cobelens8, Richard E Chaisson9, Alison D Grant10, Katherine L Fielding11. 1. The Aurum Institute, Parktown, South Africa, Vanderbilt University, Nashville, Tennessee, and University of the Witwatersrand, Johannesburg, South Africa (G.C.). 2. The Aurum Institute, Parktown, South Africa (V.C., K.M., M.S., W.B., L.M., Z.W.). 3. The Aurum Institute, Parktown, South Africa, and University of the Witwatersrand, Johannesburg, South Africa (V.C., S.C.). 4. University of the Witwatersrand, Johannesburg, South Africa, and Amsterdam University Medical Centres, Amsterdam, the Netherlands (N.M.). 5. The Ohio State University, Addis Ababa, Ethiopia (G.Y., S.W.). 6. Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique (A.L.G., D.N.). 7. KNCV Tuberculosis Foundation, Den Haag, the Netherlands, and National Institute for Public Health and the Environment, Bilthoven, the Netherlands (S.V.). 8. Amsterdam University Medical Centres, Amsterdam, the Netherlands (F.C.). 9. Johns Hopkins University, Baltimore, Maryland (R.E.C.). 10. London School of Hygiene & Tropical Medicine, London, United Kingdom, University of the Witwatersrand, Johannesburg, South Africa, and University of KwaZulu-Natal, Durban, South Africa (A.D.G.). 11. London School of Hygiene & Tropical Medicine, London, United Kingdom, and University of the Witwatersrand, Johannesburg, South Africa (K.L.F.).
Abstract
BACKGROUND: Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. OBJECTIVE: To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once. DESIGN: Randomized trial. (ClinicalTrials.gov: NCT02980016). SETTING: South Africa, Ethiopia, and Mozambique. PARTICIPANTS: Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. INTERVENTION: Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. MEASUREMENTS: Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. RESULTS: Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). LIMITATION: If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. CONCLUSION: Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. PRIMARY FUNDING SOURCE: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.
BACKGROUND: Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. OBJECTIVE: To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once. DESIGN: Randomized trial. (ClinicalTrials.gov: NCT02980016). SETTING: South Africa, Ethiopia, and Mozambique. PARTICIPANTS: Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. INTERVENTION: Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. MEASUREMENTS: Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. RESULTS: Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). LIMITATION: If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. CONCLUSION: Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. PRIMARY FUNDING SOURCE: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.
Authors: Juan F Vesga; Christian Lienhardt; Placide Nsengiyumva; Jonathon R Campbell; Olivia Oxlade; Saskia den Boon; Dennis Falzon; Kevin Schwartzman; Gavin Churchyard; Nimalan Arinaminpathy Journal: BMC Med Date: 2022-05-18 Impact factor: 11.150
Authors: Fred C Semitala; Jillian L Kadota; Allan Musinguzi; Juliet Nabunje; Fred Welishe; Anne Nakitende; Lydia Akello; Opira Bishop; Devika Patel; Amanda Sammann; Payam Nahid; Robert Belknap; Moses R Kamya; Margaret A Handley; Patrick P J Phillips; Anne Katahoire; Christopher A Berger; Noah Kiwanuka; Achilles Katamba; David W Dowdy; Adithya Cattamanchi Journal: PLoS Med Date: 2021-12-16 Impact factor: 11.613
Authors: G B Migliori; S J Wu; A Matteelli; D Zenner; D Goletti; S Ahmedov; S Al-Abri; D M Allen; M E Balcells; A L Garcia-Basteiro; E Cambau; R E Chaisson; C B E Chee; M P Dalcolmo; J T Denholm; C Erkens; S Esposito; P Farnia; J S Friedland; S Graham; Y Hamada; A D Harries; A W Kay; A Kritski; S Manga; B J Marais; D Menzies; D Ng; L Petrone; A Rendon; D R Silva; H S Schaaf; A Skrahina; G Sotgiu; G Thwaites; S Tiberi; N Tukvadze; J-P Zellweger; L D Ambrosio; R Centis; C W M Ong Journal: Int J Tuberc Lung Dis Date: 2022-03-01 Impact factor: 3.427