The Treatment of Tuberculosis in HIV-Infected Patients

Condition(s) targeted: HIV Infections; Tuberculosis

Intervention: Ethambutol hydrochloride (Drug); Isoniazid (Drug); Pyrazinamide (Drug); Pyridoxine hydrochloride (Drug); Levofloxacin (Drug); Rifampin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Perlman D, Study Chair
El-Sadr W, Study Chair

PER 5/30/95 AMENDMENT: To compare the combined rate of failure during therapy and relapse after therapy between two durations of intermittent therapy (6 versus 9 months) for the treatment of pulmonary tuberculosis (TB) in HIV-infected patients. To compare toxicity, survival, and development of resistance in these two regimens.

ORIGINAL: To compare the efficacy and safety of induction and continuation therapies for the treatment of pulmonary TB in HIV-infected patients who are either from areas with known high rates of resistance to one or more anti-TB drugs or from areas where TB is expected to be susceptible to commonly used anti-TB drugs.

PER 5/30/95 AMENDMENT: In HIV-negative patients, intermittent anti-TB therapy has been shown to be as effective as daily therapy, but the optimal duration of therapy in HIV-infected patients has not been established.

ORIGINAL: In some areas of the country, resistance to one or more of the drugs commonly used to treat TB has emerged. Thus, the need to test regimens containing a new drug exists. Furthermore, the optimal duration of anti-TB therapy for HIV-infected patients with TB needs to be determined.

Official title: The Treatment of Pulmonary Mycobacterium Tuberculosis in HIV Infection

Study design: Treatment

Detailed description: PER 5/30/95 AMENDMENT: In HIV-negative patients, intermittent anti-TB therapy has been shown to be as effective as daily therapy, but the optimal duration of therapy in HIV-infected patients has not been established.

ORIGINAL: In some areas of the country, resistance to one or more of the drugs commonly used to treat TB has emerged. Thus, the need to test regimens containing a new drug exists. Furthermore, the optimal duration of anti-TB therapy for HIV-infected patients with TB needs to be determined.

PER 5/30/95 AMENDMENT: Patients who have received an acceptable induction regimen prior to study entry and have been found to be susceptible to isoniazid and rifampin with no pyrazinamide resistance are randomized to receive either isoniazid or rifampin plus vitamin B6 biweekly for 18 or 31 weeks. Patients are evaluated at months 1, 2, 4, 6, 8, and 10, and every 4 months thereafter. Minimum follow-up is 1. 5 years.

ORIGINAL: In the induction phase, patients enrolled in "drug-susceptible" areas (defined as metropolitan areas with a resistance rate for isoniazid therapy of less than 10 percent) receive four drugs: isoniazid (plus pyridoxine), rifampin, pyrazinamide, and ethambutol. Patients enrolled in "drug-resistant" areas (resistance rate for isoniazid of 10 percent or higher) receive the four-drug regimen with or without a fifth drug, levofloxacin. After 8 weeks of induction, patients with multi-drug resistance are removed from study regimens; all other patients enter a continuation phase. Pansusceptible patients (showing susceptibility to all first-line anti-TB drugs) receive two study drugs for an additional 18 or 31 weeks; patients with isoniazid-resistant (or intolerant) TB receive two or three study drugs for an additional 44 weeks, while those with rifampin-resistant TB receive two or three study drugs for an additional 70 weeks. Patients are evaluated every 2 weeks in the induction phase and every 12 weeks in the continuation phase. Minimum follow-up is 2 years.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

Patients must have:

INDUCTION PHASE (ELIMINATED PER 5/30/95 AMENDMENT).

- HIV infection.

- Diagnosis of pulmonary TB.

NOTE:

- Patients from "susceptible" areas may be 13 years of age or older. Patients from

"resistant" areas must be 18 years of age or older.

CONTINUATION PHASE.

- Successful completion of induction phase and confirmation of TB by culture and

susceptibility results.

- Susceptibility to and tolerance of isoniazid and rifampin and no resistance to

pyrazinamide.

- HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Multi-drug resistance to at least isoniazid and rifampin or known to have had close

contact with a person with known multi-drug resistant TB.

- Known treatment-limiting reaction to any of the study drugs.

- Other disorders or conditions for which the study drugs are contraindicated.

Concurrent Medication:

Excluded:

- Other medications with anti-TB activity.

Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States

Denver CPCRA / Denver Public Hlth, Denver, Colorado 802044507, United States

Yale Univ / New Haven, New Haven, Connecticut 065102483, United States

Veterans Administration Med Ctr / Regional AIDS Program, Washington, District of Columbia 20422, United States

Howard Univ, Washington, District of Columbia 20059, United States

Univ of Miami School of Medicine, Miami, Florida 331361013, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Johns Hopkins Hosp, Baltimore, Maryland 21287, United States

State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States

Henry Ford Hosp, Detroit, Michigan 48202, United States

Comprehensive AIDS Alliance of Detroit, Detroit, Michigan 48201, United States

Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Samaritan Village Inc / Bronx Municipal Hosp, Bronx, New York 10461, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Mount Sinai Med Ctr, New York, New York 10029, United States

Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States

Cornell Univ Med Ctr, New York, New York 10021, United States

Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States

Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States

Bronx Veterans Administration / Mount Sinai Hosp, Bronx, New York 10468, United States

SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States

Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York, New York 10037, United States

Bronx Lebanon Hosp Ctr, Bronx, New York 10456, United States

Clinical Directors Network of Region II, New York, New York 10011, United States

Addiction Research and Treatment Corp, Brooklyn, New York 11201, United States

Beth Israel Med Ctr, New York, New York 10003, United States

City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States

Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States

SUNY / Health Sciences Ctr at Brooklyn, Brooklyn, New York 112032098, United States

Saint Clare's Hosp and Health Ctr, New York, New York 10019, United States

North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States

Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Columbia Presbyterian Med Ctr, New York, New York 100323784, United States

Adirondack Med Ctr at Saranac Lake, Albany, New York 122083479, United States

Mid - Hudson Care Ctr, Albany, New York 122083479, United States

Albany Med College / Division of HIV Medicine A158, Albany, New York 122083479, United States

Interfaith Med Ctr, Brooklyn, New York 112032098, United States

Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp, Bronx, New York 10461, United States

Univ of Cincinnati, Cincinnati, Ohio 452670405, United States

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Meharry Med College, Nashville, Tennessee 37203, United States

Vanderbilt Univ Med Ctr, Nashville, Tennessee 37203, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Richmond AIDS Consortium, Richmond, Virginia 23298, United States

Click here for more information about Rifampin

Click here for more information about Isoniazid

Related publications:

Telzak EE, Chirgwin K, Nelson E, Matts J, Benson C, Sepkowitz K, Perlman D, El-Sadr W. Predictors for multidrug-resistant tuberculosis (MDRTB) among HIV-infected patients and response to specific MDRTB drug regimens. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:184 (abstract no 647)

el-Sadr WM, Perlman DC, Matts JP, Nelson ET, Cohn DL, Salomon N, Olibrice M, Medard F, Chirgwin KD, Mildvan D, Jones BE, Telzak EE, Klein O, Heifets L, Hafner R. Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG). Clin Infect Dis. 1998 May;26(5):1148-58.

Perlman DC, el-Sadr WM, Nelson ET, Matts JP, Telzak EE, Salomon N, Chirgwin K, Hafner R. Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). The AIDS Clinical Trials Group (ACTG). Clin Infect Dis. 1997 Aug;25(2):242-6.

Perlman DC, El Sadr WM, Heifets LB, Nelson ET, Matts JP, Chirgwin K, Salomon N, Telzak EE, Klein O, Kreiswirth BN, Musser JM, Hafner R. Susceptibility to levofloxacin of Myocobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. Community Programs for Clinical Research on AIDS 019 and the AIDS Clinical Trials Group 222 Protocol Team. AIDS. 1997 Oct;11(12):1473-8.

Last updated: June 23, 2005