Annual Tuberculosis Preventive Therapy for Persons With HIV Infection : A Randomized Trial.

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 ( = 3610) was 90.4% versus 50.5% for the isoniazid group ( = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice ( = 1808) or once ( = 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.