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Randomized Controlled Trial
. 2016 Jun 19;30(10):1607-15.
doi: 10.1097/QAD.0000000000001098.

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons

Timothy R Sterling  1 , Nigel A Scott, Jose M Miro, Guilherme Calvet, Alberto La Rosa, Rosa Infante, Michael P Chen, Debra A Benator, Fred Gordin, Constance A Benson, Richard E Chaisson, M Elsa Villarino; Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259) The investigators of the TB Trials Consortium and the AIDS Clinical Trials Group for the PREVENT TB Trial are listed in the Supplement, item 17
Affiliations
Randomized Controlled Trial

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons

Timothy R Sterling et al. AIDS. .

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00023452.

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Conflict of interest statement

Declaration of Interests

TRS: one-day consultation for Sanofi for presentation of PREVENT TB study data to the U.S. Food and Drug Administration in 2012. Data safety monitoring board for a clinical trial sponsored by Otsuka.

NAS: employed by the CDC Foundation, which receives funds for rifapentine research from Sanofi.

JMM: Research and academic grants: Abbott, Bristol-Myers Squibb, Gilead Sciences, Merck, Novartis, ViiV Healthcare. Lectures and advisory boards: Abbott, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck, Novartis, ViiV Healthcare

GC: no conflict

AL: no conflict

RI: no conflict

MPC: no conflict

DAB: no conflict

FG: no conflict

CAB: no conflict

REC: no conflict

MEV: no conflict

Figures

Figure 1
Figure 1. Kaplan-Meier curve of time to tuberculosis by study arm in the MITT study population
The number of persons at risk at 100-day increments from enrollment are provided.
See this image and copyright information in PMC

References

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    1. Raviglione MC, Snider DE, Jr, Kochi A. Global epidemiology of tuberculosis--morbidity and mortality of a worldwide epidemic. JAMA. 1995;273:220–226. - PubMed

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