RANDOMIZED TRIAL OF ISONIAZID VERSUS RIFAMPICIN AND PYRAZINAMIDE FOR PREVENTION OF TUBERCULOSIS IN HIV-1 INFECTION

Background Tuberculosis is a common complication of HIV-1 infection, e specially in developing countries. Practical and effective chemoprophy laxis regimens for HIV-1-related tuberculosis are needed, Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. Methods We compared the efficacy of 6 months of isoniazid with 2 months of rif ampicin and pyrazinamide for prevention of tuberculosis in HIV-1-serop ositive individuals. Eligible participants were aged 16-77 years, HIV- 1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Par ticipants were randomly assigned partially supervised twice weekly iso niazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the develop ment of tuberculosis and survival. Findings Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate rati o 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tube rculosis during the first 10 months after entry was 3.7% among partici pants who received rifampicin and pyrazinamide compared with 1.0% (p=0 .03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tubercu losis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. Interp retation Twice-weekly isoniazid preventive therapy for 6 months or rif ampicin and pyrazinamide for 2 months provided similar overall protect ion against tuberculosis in HIV-1-infected, PPD-positive adults, The b etter protection among recipients of isoniazid during the first 10 mon ths was most likely secondary to the longer duration of chemoprophylax is. Preventive therapy for HIV-1-seropositive, PPD-positive individual s could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determin ed.