Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection

Neal A. Halsey, Jacqueline S. Coberly, Julio Desormeaux, Phyllis Losikoff, Joan Atkinson, Lawrence H. Moulton, Mireil Contave, Michael Johnson, Homer Davis, Lawrence Geiter, Erica Johnson, Robin Huebner, Reginald Boulos, Richard E. Chaisson

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Abstract

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. 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 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. Interpretation. 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.

Original languageEnglish (US)
Pages (from-to)786-792
Number of pages7
JournalLancet
Volume351
Issue number9105
DOIs
StatePublished - Mar 14 1998

ASJC Scopus subject areas

  • Medicine(all)

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    Halsey, N. A., Coberly, J. S., Desormeaux, J., Losikoff, P., Atkinson, J., Moulton, L. H., Contave, M., Johnson, M., Davis, H., Geiter, L., Johnson, E., Huebner, R., Boulos, R., & Chaisson, R. E. (1998). Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. Lancet, 351(9105), 786-792. https://doi.org/10.1016/S0140-6736(97)06532-X