Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial

Am J Respir Crit Care Med. 2010 Apr 1;181(7):743-51. doi: 10.1164/rccm.200903-0439OC. Epub 2009 Dec 3.


Rationale: The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear.

Objectives: To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ(3)/4HR(3) [ethambutol, 1,200 mg; isoniazid, 600 mg; rifampicin, 450 or 600 mg depending on body weight <60 or > or =60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ(3)/7HR(3)) in HIV/tuberculosis (TB).

Methods: HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment-naive during treatment.

Measurements and main results: Of the patients, 70% had culture-positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4(+) cell count was 160 cells/mm(3). Favorable response to antituberculosis treatment was similar by intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6M than in Reg9M (15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance.

Conclusions: Among antiretroviral treatment-naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment. Clinical Trials Registry Information: ID# NCT00376012 registered at www.clinicaltrials.gov.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / microbiology*
  • AIDS-Related Opportunistic Infections / virology
  • Adult
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Ethambutol / administration & dosage
  • Ethambutol / adverse effects
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / microbiology*
  • HIV Infections / virology
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / adverse effects
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Medication Adherence
  • Pyrazinamide / administration & dosage
  • Pyrazinamide / adverse effects
  • Rifampin / administration & dosage
  • Rifampin / adverse effects
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology
  • Tuberculosis / virology*
  • Viral Load / drug effects


  • Antitubercular Agents
  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin

Associated data

  • ClinicalTrials.gov/NCT00376012