The Treatment of Tuberculosis in HIV-Infected Patients - Full Text View

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections Tuberculosis	Drug: Ethambutol hydrochloride Drug: Isoniazid Drug: Pyrazinamide Drug: Pyridoxine hydrochloride Drug: Levofloxacin Drug: Rifampin	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	650 participants
Primary Purpose:	Treatment
Official Title:	The Treatment of Pulmonary Mycobacterium Tuberculosis in HIV Infection
Actual Study Completion Date :	July 1997

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Tuberculosis

U.S. FDA Resources

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:	13 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001033

Locations

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United States, California
USC CRS
Los Angeles, California, United States, 90033
United States, District of Columbia
Howard University Hosp., Div. of Infectious Diseases, ACTU
Washington, District of Columbia, United States, 20059
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, New York
SUNY - Buffalo, Erie County Medical Ctr
Buffalo, New York, United States, 14215
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Cornell University A2201
New York, New York, United States, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 10029
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

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Study Chair:	Perlman D
Study Chair:	El-Sadr W

More Information

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. doi: 10.1086/520275.

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. doi: 10.1086/514546.

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. doi: 10.1097/00002030-199712000-00011.

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Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00001033
Other Study ID Numbers:	ACTG 222 CPCRA 019 11199 ( Registry Identifier: DAIDS ES Registry Number )
First Posted:	August 31, 2001 Key Record Dates
Last Update Posted:	November 4, 2021
Last Verified:	October 2021

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


Isoniazid Tuberculosis, Pulmonary Pyrazinamide Pyridoxine Ofloxacin	Rifampin AIDS-Related Opportunistic Infections Ethambutol Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:

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Infections HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis Communicable Diseases Blood-Borne Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases	Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses Pyridoxine Vitamin B 6 Levofloxacin Rifampin Isoniazid Pyrazinamide Ethambutol Anti-Infective Agents, Urinary Anti-Infective Agents Renal Agents