Randomised 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, especially in developing countries. Practical and effective chemoprophylaxis 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 rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive 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. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival.


RESULTS
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 ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants 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 tuberculosis 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.


CONCLUSIONS
Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.
Halsey
N A
NA
Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Coberly
J S
JS
Desormeaux
J
J
Losikoff
P
P
Atkinson
J
J
Moulton
L H
LH
Contave
M
M
Johnson
M
M
Davis
H
H
Geiter
L
L
Johnson
E
E
Huebner
R
R
Boulos
R
R
Chaisson
R E
RE
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000517:prevention & control*; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D011718:Pyrazinamide / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000517:prevention & control*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin