A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus

Christopher C. Whalen, John L. Johnson, Alphonse Okwera, David L. Hom, Robin Huebner, Peter Mugyenyi, Roy D. Mugerwa, Jerrold J. Ellner, Peter Nsuhuga, Michael Vjecha, Harriet Myanja, Cissy Kityo, Anita Loughlin, John Milberg, Vukosava Pekovic

Research output: Contribution to journalArticle

Abstract

Background Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. Methods We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, ≤5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. Results Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log- rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD- positive subjects. Conclusions A six-month course of isoniazid confers short- term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.

Original languageEnglish (US)
Pages (from-to)801-808
Number of pages8
JournalNew England Journal of Medicine
Volume337
Issue number12
DOIs
StatePublished - Sep 18 1997
Externally publishedYes

Fingerprint

Isoniazid
Tuberculosis
HIV
Rifampin
Placebos
Pyrazinamide
Proteins
Confidence Intervals
Tuberculin Test
Uganda
Skin Tests
Candida
Randomized Controlled Trials
Safety
Antigens
Mortality
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Whalen, C. C., Johnson, J. L., Okwera, A., Hom, D. L., Huebner, R., Mugyenyi, P., ... Pekovic, V. (1997). A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus. New England Journal of Medicine, 337(12), 801-808. https://doi.org/10.1056/NEJM199709183371201

A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus. / Whalen, Christopher C.; Johnson, John L.; Okwera, Alphonse; Hom, David L.; Huebner, Robin; Mugyenyi, Peter; Mugerwa, Roy D.; Ellner, Jerrold J.; Nsuhuga, Peter; Vjecha, Michael; Myanja, Harriet; Kityo, Cissy; Loughlin, Anita; Milberg, John; Pekovic, Vukosava.

In: New England Journal of Medicine, Vol. 337, No. 12, 18.09.1997, p. 801-808.

Research output: Contribution to journalArticle

Whalen, CC, Johnson, JL, Okwera, A, Hom, DL, Huebner, R, Mugyenyi, P, Mugerwa, RD, Ellner, JJ, Nsuhuga, P, Vjecha, M, Myanja, H, Kityo, C, Loughlin, A, Milberg, J & Pekovic, V 1997, 'A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus', New England Journal of Medicine, vol. 337, no. 12, pp. 801-808. https://doi.org/10.1056/NEJM199709183371201
Whalen, Christopher C. ; Johnson, John L. ; Okwera, Alphonse ; Hom, David L. ; Huebner, Robin ; Mugyenyi, Peter ; Mugerwa, Roy D. ; Ellner, Jerrold J. ; Nsuhuga, Peter ; Vjecha, Michael ; Myanja, Harriet ; Kityo, Cissy ; Loughlin, Anita ; Milberg, John ; Pekovic, Vukosava. / A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus. In: New England Journal of Medicine. 1997 ; Vol. 337, No. 12. pp. 801-808.
@article{9650adbf38a24dbabcd6dbe0d009608c,
title = "A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus",
abstract = "Background Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. Methods We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, ≤5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. Results Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log- rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD- positive subjects. Conclusions A six-month course of isoniazid confers short- term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.",
author = "Whalen, {Christopher C.} and Johnson, {John L.} and Alphonse Okwera and Hom, {David L.} and Robin Huebner and Peter Mugyenyi and Mugerwa, {Roy D.} and Ellner, {Jerrold J.} and Peter Nsuhuga and Michael Vjecha and Harriet Myanja and Cissy Kityo and Anita Loughlin and John Milberg and Vukosava Pekovic",
year = "1997",
month = "9",
day = "18",
doi = "10.1056/NEJM199709183371201",
language = "English (US)",
volume = "337",
pages = "801--808",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "12",

}

TY - JOUR

T1 - A trial of three regimens to prevent tuberculosis in ugandan adults infected with the human immunodeficiency virus

AU - Whalen, Christopher C.

AU - Johnson, John L.

AU - Okwera, Alphonse

AU - Hom, David L.

AU - Huebner, Robin

AU - Mugyenyi, Peter

AU - Mugerwa, Roy D.

AU - Ellner, Jerrold J.

AU - Nsuhuga, Peter

AU - Vjecha, Michael

AU - Myanja, Harriet

AU - Kityo, Cissy

AU - Loughlin, Anita

AU - Milberg, John

AU - Pekovic, Vukosava

PY - 1997/9/18

Y1 - 1997/9/18

N2 - Background Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. Methods We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, ≤5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. Results Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log- rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD- positive subjects. Conclusions A six-month course of isoniazid confers short- term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.

AB - Background Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. Methods We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, ≤5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. Results Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log- rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD- positive subjects. Conclusions A six-month course of isoniazid confers short- term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.

UR - http://www.scopus.com/inward/record.url?scp=9844267960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9844267960&partnerID=8YFLogxK

U2 - 10.1056/NEJM199709183371201

DO - 10.1056/NEJM199709183371201

M3 - Article

C2 - 9295239

AN - SCOPUS:9844267960

VL - 337

SP - 801

EP - 808

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 12

ER -