Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults

AIDS. 2001 Nov 9;15(16):2137-47. doi: 10.1097/00002030-200111090-00009.


Background: Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens.

Methods: Three daily self-administered regimens were compared in a randomized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults. PPD-positive subjects were treated with isoniazid (INH) for 6 months (6H), INH plus rifampicin for 3 months (3HR), INH plus rifampicin and pyrazinamide for 3 months (3HRZ), or placebo for 6 months. Anergic subjects were randomized to 6H or placebo.

Results: 6H initially protected against tuberculosis in PPD-positive individuals; however, benefit was lost within the first year of treatment. Sustained benefit was observed in persons receiving 3HR and 3HRZ. In a Cox regression analysis, the adjusted relative risk for tuberculosis compared with placebo was 0.67 [95% confidence interval (CI), 0.42-1.07] for 6H, 0.49 (95% CI, 0.29-0.82) for 3HR, and 0.41 (95% CI, 0.22-0.76) for 3HRZ. When the rifampicin-containing regimens were combined, the adjusted relative risk for tuberculosis compared with placebo was 0.46 (95% CI, 0.29-0.71). Among anergic subjects, a modest degree of protection with 6H was present (adjusted relative risk, 0.61; 95% CI, 0.32-1.16). Treatment of latent tuberculosis infection had no effect on mortality.

Conclusion: Six months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / epidemiology
  • AIDS-Related Opportunistic Infections / microbiology
  • Adolescent
  • Adult
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • Humans
  • Incidence
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Pyrazinamide / pharmacology
  • Pyrazinamide / therapeutic use
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Tuberculin Test
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / microbiology


  • Antitubercular Agents
  • Pyrazinamide
  • Isoniazid
  • Rifampin