TY - JOUR
T1 - Annual Tuberculosis Preventive Therapy for Persons with HIV Infection
AU - Churchyard, Gavin
AU - Cárdenas, Vicky
AU - Chihota, Violet
AU - Mngadi, Kathy
AU - Sebe, Modulakgotla
AU - Brumskine, William
AU - Martinson, Neil
AU - Yimer, Getnet
AU - Wang, Shu-Hua
AU - Garcia-Basteiro, Alberto L.
AU - Nguenha, Dinis
AU - Masilela, LeeAnne
AU - Waggie, Zainab
AU - van den Hof, Susan
AU - Charalambous, Salome
AU - Cobelens, Frank
AU - Chaisson, Richard E.
AU - Grant, Alison D.
AU - Fielding, Katherine L.
AU - Churchyard, Gavin
AU - Cárdenas, Vicky
AU - Charalambous, Salome
AU - Chihota, Violet
AU - Waggie, Zainab
AU - Mngadi, Kathy
AU - Yates, Sarah
AU - Sikula, Jabulani
AU - Naicker, Samantha
AU - McHunu, Lihle
AU - Masilela, LeeAnne
AU - Mlokoti-Fikeni, Zonke
AU - Brumskine, William
AU - Sebe, Modulakgotla
AU - Ndebele, Felex
AU - Makkan, Heeran
AU - Ndlovu, Nontobeko
AU - Mpahlele, Phillip
AU - Mokone, Nontobeko
AU - Mngomezulu, Lerato
AU - Seatlanyane, Pule
AU - Senne, Melissa
AU - Khumalo, Siyethemba
AU - Munedzimwe, Fadzai
AU - Muthelo, Azwi
AU - Mbonisa, Fezeka
AU - Masia, Lebogang
AU - Shibambo, Kgaugelo
AU - van den Hof, Susan
AU - Cobelens, Frank
AU - The WHIP3TB Study Team
AU - Garcia-Basteiro, Alberto L.
N1 - Funding Information: Primary Funding Source: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation. Funding Information: Acknowledgment: The authors thank the thousands of study participants and the WHIP3TB teams; the North West Provincial Department of Health for generously providing office space and clinic access and for supporting the conduct of the trial; and Drs. Limakatso Lebina, Tumelo Moloantoa, and Ebrahim Variava and Mr. Itumeleng Holele for contributing to the study's success in Matlosana. This study was made possible by the generous support of the American people through USAID. Sanofi-Aventis Groupe (Paris, France) donated rifapentine and Sanofi South Africa donated isoniazid to the WHIP3TB trial. Publisher Copyright: © 2021 American College of Physicians. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85118237529&partnerID=8YFLogxK
U2 - https://doi.org/10.7326/M20-7577
DO - https://doi.org/10.7326/M20-7577
M3 - Article
C2 - 34424730
SN - 0003-4819
VL - 174
SP - 1367
EP - 1376
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 10
ER -