Hepatotoxicity of Rifampin and Pyrazinamide in the Treatment of Latent Tuberculosis Infection in HIV-Infected Persons: Is It Different Than in HIV-Uninfected Persons?

[Guest guest]

Clinical Infectious Diseases 2004;39:561-565

© 2004 by the Infectious Diseases Society of America. All rights reserved.

1058-4838/2004/3904-0022$15.00

HIV/AIDS MAJOR ARTICLE

Hepatotoxicity of Rifampin and Pyrazinamide in the Treatment of Latent

Tuberculosis Infection in HIV-Infected Persons: Is It Different Than in

HIV-Uninfected Persons?

Fred M. Gordin,1 L. Cohn,2 P. Matts,3 E. Chaisson,4 and

J. O'Brien,5 for the Terry Beirn Community Programs for Clinical

Research on AIDS, the Adult AIDS Clinical Trials Group, and the Centers for

Disease Control and Prevention

1Infectious Diseases Section, Veterans Affairs Medical Center and

Washington University, Washington, D.C.; 2Denver Health and Hospitals and

University of Colorado, Denver, Colorado; 3Division of Biostatistics, School

of Public Health, University of Minnesota, Minneapolis; 4Center for

Tuberculosis Research, s Hopkins University, Baltimore, land;

5Foundation for Innovative New Diagnostics, Geneva, Switzerland

(See the editorial commentary by Saukkonen on pages 5668)

Background. In 2000, results of a multinational trial demonstrated that

a 2-month course of rifampin and pyrazinamide (RZ) was as effective as

isoniazid (INH) in reducing tuberculosis in human immunodeficiency virus

(HIV)infected individuals with latent tuberculosis infection (LTBI). After

the release of new guidelines, the Centers for Disease Control and

Prevention received reports of severe hepatotoxicity associated with the use

of the RZ regimen for the treatment of LTBI in the general population. To

better understand the occurrence of hepatotoxicity in an HIV-infected

population, we conducted a more detailed analysis of the liver function test

results obtained in the multinational trial of RZ.

Methods. At study entry, patients were required to have a bilirubin

level of 2.5 mg/dL and both an aspartate aminotransferase (AST) level and an

alkaline phosphatase level of 5 times the upper limit of normal. Patients

with acute hepatitis were excluded. At months 1 and 2 of the study, all

patients had bilirubin and AST levels measured.

Results. There was no difference between the RZ and INH groups with

regard to AST level or bilirubin level at baseline. An increase in the AST

level of 40 U/L was associated with the use of INH and older age; and an

increase in the bilirubin level of 0.5 mg/dL was associated with the use of

RZ, male sex, and nonwhite race (P < .05). An absolute AST level of >250 U/L

occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P =

56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH

recipients and 13 of 718 RZ recipients (P = .06).

Conclusions. These data demonstrate very little liver injury

associated with either INH or RZ in the HIV-infected subjects, leaving

unclear the reasons for serious RZ-related liver damage in the general

population.

--------------------------------------------------------------------------------

Received 9 February 2004; accepted 18 March 2004; electronicallypublished 30

July 2004.

[Guest guest]

Clinical Infectious Diseases 2004;39:561-565

© 2004 by the Infectious Diseases Society of America. All rights reserved.

1058-4838/2004/3904-0022$15.00

HIV/AIDS MAJOR ARTICLE

Hepatotoxicity of Rifampin and Pyrazinamide in the Treatment of Latent

Tuberculosis Infection in HIV-Infected Persons: Is It Different Than in

HIV-Uninfected Persons?

Fred M. Gordin,1 L. Cohn,2 P. Matts,3 E. Chaisson,4 and

J. O'Brien,5 for the Terry Beirn Community Programs for Clinical

Research on AIDS, the Adult AIDS Clinical Trials Group, and the Centers for

Disease Control and Prevention

1Infectious Diseases Section, Veterans Affairs Medical Center and

Washington University, Washington, D.C.; 2Denver Health and Hospitals and

University of Colorado, Denver, Colorado; 3Division of Biostatistics, School

of Public Health, University of Minnesota, Minneapolis; 4Center for

Tuberculosis Research, s Hopkins University, Baltimore, land;

5Foundation for Innovative New Diagnostics, Geneva, Switzerland

(See the editorial commentary by Saukkonen on pages 5668)

Background. In 2000, results of a multinational trial demonstrated that

a 2-month course of rifampin and pyrazinamide (RZ) was as effective as

isoniazid (INH) in reducing tuberculosis in human immunodeficiency virus

(HIV)infected individuals with latent tuberculosis infection (LTBI). After

the release of new guidelines, the Centers for Disease Control and

Prevention received reports of severe hepatotoxicity associated with the use

of the RZ regimen for the treatment of LTBI in the general population. To

better understand the occurrence of hepatotoxicity in an HIV-infected

population, we conducted a more detailed analysis of the liver function test

results obtained in the multinational trial of RZ.

Methods. At study entry, patients were required to have a bilirubin

level of 2.5 mg/dL and both an aspartate aminotransferase (AST) level and an

alkaline phosphatase level of 5 times the upper limit of normal. Patients

with acute hepatitis were excluded. At months 1 and 2 of the study, all

patients had bilirubin and AST levels measured.

Results. There was no difference between the RZ and INH groups with

regard to AST level or bilirubin level at baseline. An increase in the AST

level of 40 U/L was associated with the use of INH and older age; and an

increase in the bilirubin level of 0.5 mg/dL was associated with the use of

RZ, male sex, and nonwhite race (P < .05). An absolute AST level of >250 U/L

occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P =

56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH

recipients and 13 of 718 RZ recipients (P = .06).

Conclusions. These data demonstrate very little liver injury

associated with either INH or RZ in the HIV-infected subjects, leaving

unclear the reasons for serious RZ-related liver damage in the general

population.

--------------------------------------------------------------------------------

Received 9 February 2004; accepted 18 March 2004; electronicallypublished 30

July 2004.

[Guest guest]

Clinical Infectious Diseases 2004;39:561-565

© 2004 by the Infectious Diseases Society of America. All rights reserved.

1058-4838/2004/3904-0022$15.00

HIV/AIDS MAJOR ARTICLE

Hepatotoxicity of Rifampin and Pyrazinamide in the Treatment of Latent

Tuberculosis Infection in HIV-Infected Persons: Is It Different Than in

HIV-Uninfected Persons?

Fred M. Gordin,1 L. Cohn,2 P. Matts,3 E. Chaisson,4 and

J. O'Brien,5 for the Terry Beirn Community Programs for Clinical

Research on AIDS, the Adult AIDS Clinical Trials Group, and the Centers for

Disease Control and Prevention

1Infectious Diseases Section, Veterans Affairs Medical Center and

Washington University, Washington, D.C.; 2Denver Health and Hospitals and

University of Colorado, Denver, Colorado; 3Division of Biostatistics, School

of Public Health, University of Minnesota, Minneapolis; 4Center for

Tuberculosis Research, s Hopkins University, Baltimore, land;

5Foundation for Innovative New Diagnostics, Geneva, Switzerland

(See the editorial commentary by Saukkonen on pages 5668)

Background. In 2000, results of a multinational trial demonstrated that

a 2-month course of rifampin and pyrazinamide (RZ) was as effective as

isoniazid (INH) in reducing tuberculosis in human immunodeficiency virus

(HIV)infected individuals with latent tuberculosis infection (LTBI). After

the release of new guidelines, the Centers for Disease Control and

Prevention received reports of severe hepatotoxicity associated with the use

of the RZ regimen for the treatment of LTBI in the general population. To

better understand the occurrence of hepatotoxicity in an HIV-infected

population, we conducted a more detailed analysis of the liver function test

results obtained in the multinational trial of RZ.

Methods. At study entry, patients were required to have a bilirubin

level of 2.5 mg/dL and both an aspartate aminotransferase (AST) level and an

alkaline phosphatase level of 5 times the upper limit of normal. Patients

with acute hepatitis were excluded. At months 1 and 2 of the study, all

patients had bilirubin and AST levels measured.

Results. There was no difference between the RZ and INH groups with

regard to AST level or bilirubin level at baseline. An increase in the AST

level of 40 U/L was associated with the use of INH and older age; and an

increase in the bilirubin level of 0.5 mg/dL was associated with the use of

RZ, male sex, and nonwhite race (P < .05). An absolute AST level of >250 U/L

occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P =

56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH

recipients and 13 of 718 RZ recipients (P = .06).

Conclusions. These data demonstrate very little liver injury

associated with either INH or RZ in the HIV-infected subjects, leaving

unclear the reasons for serious RZ-related liver damage in the general

population.

--------------------------------------------------------------------------------

Received 9 February 2004; accepted 18 March 2004; electronicallypublished 30

July 2004.

[Guest guest]

Clinical Infectious Diseases 2004;39:561-565

© 2004 by the Infectious Diseases Society of America. All rights reserved.

1058-4838/2004/3904-0022$15.00

HIV/AIDS MAJOR ARTICLE

Hepatotoxicity of Rifampin and Pyrazinamide in the Treatment of Latent

Tuberculosis Infection in HIV-Infected Persons: Is It Different Than in

HIV-Uninfected Persons?

Fred M. Gordin,1 L. Cohn,2 P. Matts,3 E. Chaisson,4 and

J. O'Brien,5 for the Terry Beirn Community Programs for Clinical

Research on AIDS, the Adult AIDS Clinical Trials Group, and the Centers for

Disease Control and Prevention

1Infectious Diseases Section, Veterans Affairs Medical Center and

Washington University, Washington, D.C.; 2Denver Health and Hospitals and

University of Colorado, Denver, Colorado; 3Division of Biostatistics, School

of Public Health, University of Minnesota, Minneapolis; 4Center for

Tuberculosis Research, s Hopkins University, Baltimore, land;

5Foundation for Innovative New Diagnostics, Geneva, Switzerland

(See the editorial commentary by Saukkonen on pages 5668)

Background. In 2000, results of a multinational trial demonstrated that

a 2-month course of rifampin and pyrazinamide (RZ) was as effective as

isoniazid (INH) in reducing tuberculosis in human immunodeficiency virus

(HIV)infected individuals with latent tuberculosis infection (LTBI). After

the release of new guidelines, the Centers for Disease Control and

Prevention received reports of severe hepatotoxicity associated with the use

of the RZ regimen for the treatment of LTBI in the general population. To

better understand the occurrence of hepatotoxicity in an HIV-infected

population, we conducted a more detailed analysis of the liver function test

results obtained in the multinational trial of RZ.

Methods. At study entry, patients were required to have a bilirubin

level of 2.5 mg/dL and both an aspartate aminotransferase (AST) level and an

alkaline phosphatase level of 5 times the upper limit of normal. Patients

with acute hepatitis were excluded. At months 1 and 2 of the study, all

patients had bilirubin and AST levels measured.

Results. There was no difference between the RZ and INH groups with

regard to AST level or bilirubin level at baseline. An increase in the AST

level of 40 U/L was associated with the use of INH and older age; and an

increase in the bilirubin level of 0.5 mg/dL was associated with the use of

RZ, male sex, and nonwhite race (P < .05). An absolute AST level of >250 U/L

occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P =

56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH

recipients and 13 of 718 RZ recipients (P = .06).

Conclusions. These data demonstrate very little liver injury

associated with either INH or RZ in the HIV-infected subjects, leaving

unclear the reasons for serious RZ-related liver damage in the general

population.

--------------------------------------------------------------------------------

Received 9 February 2004; accepted 18 March 2004; electronicallypublished 30

July 2004.