Na. Halsey et al., RANDOMIZED TRIAL OF ISONIAZID VERSUS RIFAMPICIN AND PYRAZINAMIDE FOR PREVENTION OF TUBERCULOSIS IN HIV-1 INFECTION, Lancet, 351(9105), 1998, pp. 786-792
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.