Rifabutin for the treatment of newly-diagnosed pulmonary tuberculosis: a multinational, randomized, comparative study versus Rifampicin. Rifabutin Study Group. A pilot study of antituberculosis combinations comparing rifabutin with rifampicin in the treatment of HIV-1 associated tuberculosis. A single-blind randomized evaluation in Ugandan patients with HIV-1 infection and pulmonary tuberculosis. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group. Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus? Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up.
Patients with newly-diagnosed drug-sensitive, radiographically active and bacteriologically confirmed pulmonary tuberculosis recruited at 6 centres in Argentina, Brazil and Thailand.
                To assess the efficacy, tolerability and toxicity of two regimens containing different daily dosages of rifabutin in comparison with rifampicin.
                Multicentred, randomised, comparative study. In each group, study medications were administered daily for 6 months combined with isoniazid (6 months), and with pyrazinamide and ethambutol (both stopped after 2 months). Treatment success patients were followed-up for up to 2 years.
                A total of 520 patients were enrolled and randomly assigned to receive either rifampicin (n = 175), or rifabutin 150 mg (n = 174) or rifabutin 300 mg (n = 171). Considering all patients with positive baseline culture, the success rates at the last valid observation for each patient were 89%, 94% and 92% in the rifampicin, rifabutin 150 mg, and rifabutin 300 mg groups, respectively. The median time to culture conversion was comparable in the 3 groups and was 34 days for rifampicin and 37 days for each of the rifabutin groups. During the drug-free follow-up period, one relapse occurred in the rifampicin group, and two in each of the rifabutin groups. The 3 treatment schedules appeared well tolerated. No patients had to discontinue therapy because of an adverse event in the rifabutin 150 mg group, compared to one in the rifampicin and 5 in the rifabutin 300 mg group.
                All 3 regimens proved effective and well tolerated. Rifabutin at 150 mg/d showed the best risk-to-benefit ratio, in that this group had the highest proportion of patients completing treatment, the highest bacteriological conversion rates and the lowest incidence of adverse events. This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic.
                To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB.
                Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide.
                Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated with a longer sputum conversion time for patients treated with either regimen. No major adverse events requiring dosage reduction or withdrawal of any study medication were seen in either treatment group. Mean absolute peripheral blood CD4 T lymphocyte counts increased by 28% from week 0 to week 12 in all subjects (334-427/microliters, respectively). An unexpected finding was the isolation of Mycobacterium africanum from 49% of the sputum cultures. This is the first report indicating a high prevalence of M. africanum in human TB in Uganda.
                Short-course antituberculosis regimens containing rifabutin or rifampicin are both safe and efficacious in the treatment of HIV-1 associated tuberculosis. Rifabutin-containing regimens were associated with earlier sputum smear and culture conversion. Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed.
                To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection.
                Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997.
                Outpatient clinics in the United States, Mexico, Haiti, and Brazil.
                A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result.
                Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791).
                The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group.
                Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis.
                Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs. Nine public health care centres in four Spanish cities.
                To evaluate the efficacy and safety of 2 months of rifampicin (R) plus pyrazinamide (Z) therapy (2RZ) compared with a 6-month course of isoniazid therapy (6H) for treating latent tuberculosis infection (LTBI).
                Multicentered, randomised, comparative and prospective trial conducted in HIV-seronegative contacts of infectious pulmonary TB cases.
                Of 352 individuals, 199 received 6H and 153 2RZ; 73% of contacts receiving 6H and 71% receiving 2RZ completed treatment (P = 0.73). Treatment interruption due to hepatotoxicity (ALT/AST > 5 times upper limit of normal) was observed in 10% of contacts in the 2RZ group and in 2.5% of the 6H group (P = 0.007). This higher than expected rate of hepatotoxicity in the 2RZ arm led to premature termination of the study. Severe or fatal liver injury was not detected. Liver function tests normalised after discontinuation of treatment. We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible. A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.
The replacement of rifampicin by rifabutin for first-line treatment of tuberculosis is not supported by the current evidence. HIV-positive people with tuberculosis, the group most likely to benefit from the rifabutin use, are under-represented in trials to date, and further trials in this group would be useful.