title: Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial.
abstract: BACKGROUND
  The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: Tuberculosis Research Center, Indian Council of Medical Research, Chetput, Chennai, India. doctorsoumya@yahoo.com
authors: Soumya
authors: S
authors: Swaminathan
authors: Gopalan
authors: G
authors: Narendran
authors: Perumal
authors: P
authors: Venkatesan
authors: Sheik
authors: S
authors: Iliayas
authors: Rameshkumar
authors: R
authors: Santhanakrishnan
authors: Pradeep Aravindan
authors: PA
authors: Menon
authors: Chandrasekharan
authors: C
authors: Padmapriyadarsini
authors: Ranjani
authors: R
authors: Ramachandran
authors: Ponnuraja
authors: P
authors: Chinnaiyan
authors: Mohanarani
authors: M
authors: Suhadev
authors: Raja
authors: R
authors: Sakthivel
authors: Paranji R
authors: PR
authors: Narayanan
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000821:virology; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000382:microbiology* / Q000821:virology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000821:virology*; D019562:Viral Load / Q000187:drug effects
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin