Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

October 26, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis.

Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Patients are chosen by a random selection process to either the INH or the rifampin / pyrazinamide arm of the dose. Patients on the INH arm receive INH plus vitamin B6 (pyridoxine hydrochloride ) daily for 12 months. Patients on the other arm receive rifampin plus pyrazinamide for 60 days. Dosage of rifampin and pyrazinamide depends on weight of patient.

Study Type

Interventional

Enrollment

2000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 009365067
        • Univ of Puerto Rico
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hosp of Los Angeles
      • Los Angeles, California, United States, 900331079
        • Univ of Southern California / LA County USC Med Ctr
      • Oakland, California, United States, 946021018
        • Highland Gen Hosp / San Francisco Gen Hosp
      • San Francisco, California, United States, 94115
        • Stanford at Kaiser / Kaiser Permanente Med Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco Gen Hosp
      • San Jose, California, United States, 951282699
        • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
      • Stanford, California, United States, 943055107
        • San Mateo AIDS Program / Stanford Univ
      • Stanford, California, United States, 943055107
        • Stanford Univ Med Ctr
      • Sylmar, California, United States, 91342
        • Olive View Med Ctr
      • Torrance, California, United States, 90502
        • Harbor UCLA Med Ctr
    • Connecticut
      • New Haven, Connecticut, United States, 065102483
        • Yale Univ / New Haven
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown Univ Med Ctr
      • Washington, District of Columbia, United States, 20059
        • Howard Univ
      • Washington, District of Columbia, United States, 200072197
        • HIV Ctr - District of Columbia Gen Hosp
      • Washington, District of Columbia, United States, 200072197
        • Whitman - Walker Clinic / Georgetown Univ Med Ctr
    • Florida
      • Miami, Florida, United States, 331361013
        • Univ of Miami School of Medicine
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ of Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Queens Med Ctr
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
      • Chicago, Illinois, United States, 60640
        • Louis A Weiss Memorial Hosp
      • Chicago, Illinois, United States, 60611
        • Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hosp
      • Baltimore, Maryland, United States, 212052196
        • State of MD Div of Corrections / Johns Hopkins Univ Hosp
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - West Campus
      • Springfield, Massachusetts, United States, 01199
        • Baystate Med Ctr of Springfield
    • Missouri
      • Saint Louis, Missouri, United States, 63112
        • St Louis Regional Hosp / St Louis Regional Med Ctr
    • Nebraska
      • Omaha, Nebraska, United States, 681985130
        • Univ of Nebraska Med Ctr
    • New Jersey
      • Newark, New Jersey, United States, 071032714
        • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
      • Newark, New Jersey, United States, 071072198
        • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
    • New York
      • Albany, New York, United States, 122083479
        • Albany Med College / Division of HIV Medicine A158
      • Albany, New York, United States, 122083479
        • Adirondack Med Ctr at Saranac Lake
      • Albany, New York, United States, 122083479
        • Mid - Hudson Care Ctr
      • Bronx, New York, United States, 10461
        • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
      • Bronx, New York, United States, 10465
        • Jack Weiler Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • Montefiore Med Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • Montefiore Med Ctr Adolescent AIDS Program
      • Bronx, New York, United States, 10461
        • Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Montefiore Family Health Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Samaritan Village Inc / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • North Central Bronx Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Comprehensive Health Care Ctr / Bronx Municipal Hosp
      • Brooklyn, New York, United States, 112032098
        • SUNY / Health Sciences Ctr at Brooklyn
      • Brooklyn, New York, United States, 112032098
        • Interfaith Med Ctr
      • Buffalo, New York, United States, 14215
        • SUNY / Erie County Med Ctr at Buffalo
      • East Meadow, New York, United States, 11554
        • Nassau County Med Ctr
      • Elmhurst, New York, United States, 11373
        • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
      • Manhasset, New York, United States, 11030
        • North Shore Univ Hosp
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr
      • New York, New York, United States, 10021
        • Cornell Univ Med Ctr
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10025
        • Saint Luke's - Roosevelt Hosp Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • New York, New York, United States, 100323784
        • Columbia Presbyterian Med Ctr
      • New York, New York, United States, 10019
        • Saint Clare's Hosp and Health Ctr
      • Stony Brook, New York, United States, 117948153
        • SUNY - Stony Brook
      • Syracuse, New York, United States, 13210
        • SUNY / State Univ of New York
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Greensboro, North Carolina, United States, 27401
        • Moses H Cone Memorial Hosp
      • Raleigh, North Carolina, United States, 27610
        • Wake County Dept of Health
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
      • Cincinnati, Ohio, United States, 45267
        • Univ of Kentucky Lexington
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Cleveland, Ohio, United States, 441091998
        • MetroHealth Med Ctr
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania at Philadelphia
      • Philadelphia, Pennsylvania, United States, 191075098
        • Thomas Jefferson Univ Hosp
      • Philadelphia, Pennsylvania, United States, 191046073
        • Girard Med Ctr
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Med Univ of South Carolina / UNC
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Meharry Med College
    • Texas
      • Galveston, Texas, United States, 775550435
        • Univ of Texas Galveston
      • Houston, Texas, United States, 77266
        • Houston Clinical Research Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Antiretroviral treatment.
  • Pneumocystis carinii pneumonia prophylaxis.
  • Treatment for acute opportunistic infection.

Patients must have:

  • HIV infection.
  • Current or documented history of positive PPD skin test.
  • Life expectancy of at least 6 months or, in the physician's opinion, patient has a reasonable chance of survival to end of study.

Allowed:

  • Participation in other clinical trials as long as there is no potential activity of other study drugs against Mycobacterium tuberculosis (MTb), additive toxicities between study agents, or known possible drug interactions between study drugs.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Current active clinical tuberculosis, confirmed or suspected.
  • History of sensitivity / intolerance to any study medication.
  • Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.
  • Unwilling or unable to have current therapy and/or concomitant medication changed to avoid serious interaction with study medication.
  • Acute hepatitis.
  • Unable to comply with the follow-up requirements of the protocol.

Concurrent Medication:

Excluded:

  • Treatment with quinolones, fluoroquinolones, aminoglycosides, or other agents that have activity against Mycobacterium tuberculosis.
  • Excluded as ongoing (i.e., continuous, chronic and/or recurring) treatment:
  • Aminoglycosides such as amikacin, aminosalicylic acid salts (PAS), capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid (INH) if randomized to rifampin/pyrazinamide arm of study, kanamycin, pyrazinamide if randomized to INH arm of study, and quinolones and fluoroquinolones, i.e., rifabutin, rifampin (if randomized to INH arm of study), ciprofloxacin, levofloxacin, ofloxacin, streptomycin, and thiacetazone.

Prior Medication:

Excluded:

  • More than 2 months of continuous treatment, after documentation of a positive PPD skin test, with agents that have known or potential antituberculous activity or any antimycobacterial medication for > 1 month.

Patients may not have the following prior conditions:

  • History of sensitivity / intolerance to any study medication.
  • Unwilling or unable to comply with the follow-up requirements of the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Interventional Model: PARALLEL

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Lederle Laboratories
Hoechst Marion Roussel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (ACTUAL)

September 1, 1999

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ACTUAL)

November 2, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 177
  • 11152 (REGISTRY: DAIDS ES Registry Number)
  • CPCRA 004
  • TB/PPD+

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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