Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons
HIV; isoniazid; latent tuberculosis; Mycobacterium tuberculosis; rifapentine
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Objective: Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected persons. Design: Prospective, randomized, and open-label noninferiority trial. Setting: The United States, Brazil, Spain, Peru, Canada, and Hong Kong. Participants: HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases. Intervention: 3HP versus 9H. Main outcome measures: The effectiveness endpoint was tuberculosis; the noninferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation because of adverse drug reaction. Results: Median baseline CD4 + cell counts were 495 (IQR 389-675) and 538 (IQR 418-729) cells/μl in the 3HP and 9H arms, respectively (P = 0.09). In the modified intention-to-treat analysis, there were two tuberculosis cases among 206 persons [517 person-years (p-y) of follow-up] in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01 versus 3.50% in the 3HP and 9H arms, respectively (rate difference: -2.49%; upper bound of the 95% confidence interval of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P < 0.001), and drug discontinuation because of an adverse drug reaction was similar (3 vs. 4%; P = 0.79) in 3HP and 9H, respectively. Conclusion: Among HIV-infected persons with median CD4 + cell count of approximately 500 cells/μl, 3HP was as effective and safe for treatment of latent Mycobacterium tuberculosis infection as 9H, and better tolerated.
Sterling, T., Scott, N., Miro, J., Calvet, G., La Rosa, A., Infante, R., Chen, M., Benator, D., Gordin, F., Benson, C., Chaisson, R., & Villarino, M. (2016). Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS, 30 (10). http://dx.doi.org/10.1097/QAD.0000000000001098