Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts.
BACKGROUND
Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies.


OBJECTIVE
To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil.


METHODS
Contacts of patients with TB were randomized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450-600 mg/pyrazinamide 750-1,500 mg daily for 8 wk and followed for at least 2 yr.


METHODS
TB rates, adverse events, and adherence to therapy.


RESULTS
A total of 399 household contacts were enrolled, 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm. The median age was 34 yr, median weight was 63 kg, 60% of participants were female, and only one patient was HIV infected. Rifapentine/isoniazid was well tolerated, but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm. Twenty of 193 participants (10%) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity, compared with 2 of 206 participants (1%) on rifapentine/isoniazid (p<0.001). There were no hospitalizations or deaths due to hepatotoxicity, and all participants' liver enzyme levels returned to normal during follow-up. During follow-up, four cases of active TB developed, three in the rifapentine/isoniazid group and one in the rifampin/pyrazinamide group (1.46 vs. 0.52%; difference, 0.94%; 95% confidence interval, -1.6 to 3.7%).


CONCLUSIONS
Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.
Infectious Diseases Service, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
Mauro
M
Schechter
Roberto
R
Zajdenverg
Gisely
G
Falco
Grace Link
GL
Barnes
José Cláudio
JC
Faulhaber
Jacqueline S
JS
Coberly
Richard D
RD
Moore
Richard E
RE
Chaisson
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011718:Pyrazinamide / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission
D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine