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

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


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: NCT00023452.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Americas
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • Asia
  • Child
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • HIV Infections / complications*
  • Humans
  • Isoniazid / administration & dosage*
  • Isoniazid / adverse effects
  • Male
  • Prospective Studies
  • Rifampin / administration & dosage
  • Rifampin / adverse effects
  • Rifampin / analogs & derivatives*
  • Treatment Outcome
  • Tuberculosis / complications*
  • Tuberculosis / drug therapy*
  • Young Adult


  • Antitubercular Agents
  • Isoniazid
  • Rifampin
  • rifapentine

Associated data