This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (123)  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in JAMA  Social Bookmarking   What's this?

An International Randomized Trial

Fred Gordin, MD; Richard E. Chaisson, MD; John P. Matts, PhD; Carol Miller, MPH; Maria de Lourdes Garcia, MD, PhD; Richard Hafner, MD; Jose Luis Valdespino, MD, MPH; Jacqueline Coberly, PhD; Mauro Schechter, MD, PhD; Alan J. Klukowicz, MD; M. Anita Barry, MD, MPH; Richard J. O'Brien, MD; for the Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group

JAMA. 2000;283:1445-1450.

Context  Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed.

Objective  To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection.

Design  Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997.

Setting  Outpatient clinics in the United States, Mexico, Haiti, and Brazil.

Participants  A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result.

Interventions  Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791).

Main Outcome Measures  The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group.

Results  Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis.

Conclusions  Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.

Author Affiliations: Veterans Affairs Medical Center and Georgetown University, Washington, DC (Dr Gordin); the Department of Medicine, School of Medicine (Dr Chaisson), and Department of International Health, School of Hygiene and Public Health (Dr Coberly), Johns Hopkins University, Baltimore, Md; the Community Programs for Clinical Research on AIDS Statistical Center and Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis (Dr Matts and Ms Miller); the National Institute of Public Health, Cuernavaca, Mexico (Drs Garcia and Valdespino); the Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Md (Dr Hafner); Infectious Diseases Service, Hospital Universitário Clementino Fraga Filho, Department of Preventive Medicine, Universidade Federal do Rio de Janeiro, Brazil (Dr Schechter); Pulmonary Division, Saint Michael's Medical Center, Newark, NJ (Dr Klukowicz); Communicable Disease Control, Boston Public Health Commission, Boston, Mass (Dr Barry); and the Division of Tuberculosis Elimination, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Ga (Dr O'Brien).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED LETTER

Long-term Obligations to Human Subjects in Clinical Trials
Jose Luis Valdespino-Gomez, Maria de Lourdes Garcia-Garcia, and Manuel Palacios-Martinez
JAMA. 2000;284(8):960-961.
EXTRACT | FULL TEXT  

RELATED ARTICLE

March 15, 2000
JAMA. 2000;283(11):1497-1498.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Do We Have Evidence for Policy Changes in the Treatment of Children With Latent Tuberculosis Infection?
Lobato et al.
Pediatrics 2009;123:902-903.
FULL TEXT  

Adverse Events with 4 Months of Rifampin Therapy or 9 Months of Isoniazid Therapy for Latent Tuberculosis Infection: A Randomized Trial
Menzies et al.
ANN INTERN MED 2008;149:689-697.
ABSTRACT | FULL TEXT  

Needed: New and Better Tools to Combat Latent Tuberculosis Infection
Blumberg
ANN INTERN MED 2008;149:761-763.
FULL TEXT  

HIV-related TB and adverse drug events
Leung et al.
Thorax 2007;62:923-924.
FULL TEXT  

TUBERCULOSIS MORTALITY, DRUG RESISTANCE, AND INFECTIOUSNESS IN PATIENTS WITH AND WITHOUT HIV INFECTION IN PERU
KAWAI et al.
Am J Trop Med Hyg 2006;75:1027-1033.
ABSTRACT | FULL TEXT  

An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy.
Saukkonen et al.
Am. J. Respir. Crit. Care Med. 2006;174:935-952.
ABSTRACT | FULL TEXT  

Improved Adherence and Less Toxicity With Rifampin vs Isoniazid for Treatment of Latent Tuberculosis: A Retrospective Study.
Page et al.
Arch Intern Med 2006;166:1863-1870.
ABSTRACT | FULL TEXT  

The Fight Against Tuberculosis
Scheindlin
Mol. Interv. 2006;6:124-130.
FULL TEXT  

Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts
Schechter et al.
Am. J. Respir. Crit. Care Med. 2006;173:922-926.
ABSTRACT | FULL TEXT  

Rifapentine, Moxifloxacin, or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse Model
Nuermberger et al.
Am. J. Respir. Crit. Care Med. 2005;172:1452-1456.
ABSTRACT | FULL TEXT  

American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Controlling Tuberculosis in the United States
Am. J. Respir. Crit. Care Med. 2005;172:1169-1227.
FULL TEXT  

Isoniazid Hepatotoxicity Associated With Treatment of Latent Tuberculosis Infection: A 7-Year Evaluation From a Public Health Tuberculosis Clinic
Fountain et al.
Chest 2005;128:116-123.
ABSTRACT | FULL TEXT  

Update on the Treatment of Tuberculosis and Latent Tuberculosis Infection
Blumberg et al.
JAMA 2005;293:2776-2784.
ABSTRACT | FULL TEXT  

Hepatotoxicity from pyrazinamide based anti-tuberculous therapy: protective effect from isoniazid and HIV infection?
Boyd
Thorax 2005;60:210-210.
FULL TEXT  

Considering the Role of Four Months of Rifampin in the Treatment of Latent Tuberculosis Infection
Reichman et al.
Am. J. Respir. Crit. Care Med. 2004;170:832-835.
FULL TEXT  

Treatment Completion and Costs of a Randomized Trial of Rifampin for 4 Months versus Isoniazid for 9 Months
Menzies et al.
Am. J. Respir. Crit. Care Med. 2004;170:445-449.
ABSTRACT | FULL TEXT  

Initial Experience on Rifampin and Pyrazinamide vs Isoniazid in the Treatment of Latent Tuberculosis Infection Among Patients With Silicosis in Hong Kong
Leung et al.
Chest 2003;124:2112-2118.
ABSTRACT | FULL TEXT  

Use of Isoniazid for Latent Tuberculosis Infection in a Public Health Clinic
LoBue and Moser
Am. J. Respir. Crit. Care Med. 2003;168:443-447.
ABSTRACT | FULL TEXT  

Incidence of Serious Side Effects from First-Line Antituberculosis Drugs among Patients Treated for Active Tuberculosis
Yee et al.
Am. J. Respir. Crit. Care Med. 2003;167:1472-1477.
ABSTRACT | FULL TEXT  

Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection: Is It Safe?
Jasmer and Daley
Am. J. Respir. Crit. Care Med. 2003;167:809-810.
FULL TEXT  

Safety of 2 Months of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis
Stout et al.
Am. J. Respir. Crit. Care Med. 2003;167:824-827.
ABSTRACT | FULL TEXT  

Pyrazinamide and Rifampin vs Isoniazid for the Treatment of Latent Tuberculosis: Improved Completion Rates But More Hepatotoxicity
McNeill et al.
Chest 2003;123:102-106.
ABSTRACT | FULL TEXT  

Global Drug-Resistance Patterns and the Management of Latent Tuberculosis Infection in Immigrants to the United States
Khan et al.
NEJM 2002;347:1850-1859.
ABSTRACT | FULL TEXT  

Latent Tuberculosis Infection
Jasmer et al.
NEJM 2002;347:1860-1866.
FULL TEXT  

Short-Course Rifampin and Pyrazinamide Compared with Isoniazid for Latent Tuberculosis Infection: A Multicenter Clinical Trial
Jasmer et al.
ANN INTERN MED 2002;137:640-647.
ABSTRACT | FULL TEXT  

Short-Course Rifamycin and Pyrazinamide Treatment for Latent Tuberculosis Infection in Patients With HIV Infection: The 2-Year Experience of a Comprehensive Community-Based Program in Broward County, Florida
Narita et al.
Chest 2002;122:1292-1298.
ABSTRACT | FULL TEXT  

Safety and Tolerability of Intermittent Rifampin/Pyrazinamide for the Treatment of Latent Tuberculosis Infection in Prisoners
Chaisson et al.
JAMA 2002;288:165-166.
FULL TEXT  

Challenges of Treating Latent Tuberculosis Infection
Schluger
Chest 2002;121:1733-1735.
FULL TEXT  

Death Associated With Rifampin and Pyrazinamide 2-Month Treatment of Latent Mycobacterium Tuberculosis*
Medinger
Chest 2002;121:1710-1712.
ABSTRACT | FULL TEXT  

European framework for tuberculosis control and elimination in countries with a low incidence: Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group
Broekmans et al.
Eur Respir J 2002;19:765-775.
ABSTRACT | FULL TEXT  

Latent tuberculosis infection: old problem, new priorities
Schwartzman
CMAJ 2002;166:759-761.
FULL TEXT  

Tuberculosis and HIV
AIDS Clin Care 2002;2002:6-6.
FULL TEXT  

Pulmonary Complications of HIV Infection . Report of the Fourth NHLBI Workshop
BECK et al.
Am. J. Respir. Crit. Care Med. 2001;164:2120-2126.
FULL TEXT  

Update: Fatal and Severe Liver Injuries Associated With Rifampin and Pyrazinamide for Latent Tuberculosis Infection, and Revisions in American Thoracic Society/ CDC Recommendations-United States, 2001 . This Official American Thoracic Society/Centers For Disease Control and Prevention (ATS/CDC) Update was Approved by the ATS Executive Committee, August 2001
Am. J. Respir. Crit. Care Med. 2001;164:1319-1320.
FULL TEXT  

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study
Antonucci et al.
Eur Respir J 2001;18:369-375.
ABSTRACT | FULL TEXT  

Management of Tuberculosis in the United States
Small and Fujiwara
NEJM 2001;345:189-200.
FULL TEXT  

Acceptability of Short-Course Rifampin and Pyrazinamide Treatment of Latent Tuberculosis Infection Among Jail Inmates
Bock et al.
Chest 2001;119:833-837.
ABSTRACT | FULL TEXT  

Additional articles abstracted in ACP Journal Club
Evid. Based Med. 2000;5:163-163.
FULL TEXT  

Long-term Obligations to Human Subjects in Clinical Trials
Valdespino-Gomez et al.
JAMA 2000;284:960-961.
FULL TEXT  

Short-Course Preventive Therapy for TB
AIDS Clin Care 2000;2000:3-3.
FULL TEXT  

Prophylaxis against Opportunistic Infections in Patients with Human Immunodeficiency Virus Infection
Kovacs and Masur
NEJM 2000;342:1416-1429.
FULL TEXT  

Rifampin-Pyrazinamide Regimen Prevents TB in HIV-Positive Patients
JWatch Infect. Diseases 2000;2000:8-8.
FULL TEXT  

Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection . This Official Statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This Statement was endorsed by the Council of the Infectious Diseases Society of America (IDSA), September 1999, and the sections of this Statement as it relates to infants and children were endorsed by the American Academy of Pediatrics (AAP), August 1999.
Am. J. Respir. Crit. Care Med. 2000;161:S221-247.
FULL TEXT  

Rifampin and Pyrazinamide to Prevent TB
JWatch General 2000;2000:2-2.
FULL TEXT