NIAID has launched the first large U.S. study to assess tuberculosis treatment for those with both active TB and HIV infections. Up to 650 people will enroll in two NIAID nationwide trial networks.
The National Institute of Allergy and Infectious Diseases has launched the first large U.S. study to assess tuberculosis treatment strategies for persons infected with both tuberculosis and HIV, the virus that causes AIDS.
Study investigators will enroll up to 650 HIV-infected persons with active tuberculosis in two nationwide clinical trials networks supported by NIAID. The networks are the AIDS Clinical Trials Group and the Terry Beirn Community Programs for Clinical Research on AIDS.
HHS Secretary Donna E. Shalala said, "TB has re-emerged in the United States as a serious public health problem, and disproportionately affects the most vulnerable in our society. We are committed to fighting this epidemic. In order to contain the further spread of this disease, we must identify persons with TB and treat them successfully."
TB is an airborne disease, primarily of the lungs. Because of their weakened immune systems, persons with the human immunodeficiency virus are particularly vulnerable to reactivation of latent TB infections, as well as new TB infections. TB transmission occurs most frequently in crowded environments such as hospitals, prisons and shelters -- places where HIV-infected individuals make up a growing proportion of the population.
This study will provide state-of-the-art treatment to HIV-infected persons with tuberculosis and answer important questions about the management of these patients," said NIAID director Anthony S. Fauci, M.D. "Although we anticipate enrolling patients nationwide, it is likely that a significant proportion of the patients will be enrolled in New York City, where TB, especially drug-resistant TB, is a persistent and growing problem."
In 1991, the Centers for Disease Control and Prevention received reports of 26,283 active TB cases in the United States, an increase of 18 percent since 1985. Each year, eight million people worldwide develop active TB, and three million die, according to the World Health Organization.
The CDC estimates that 100,000 individuals in the United States are infected with both HIV and the TB bacterium. Worldwide, the WHO estimates that 4.4 million people are co-infected with HIV and TB.
Drug-resistant cases of TB have increased dramatically in the past few years. Drug resistance results when patients fail to take their TB medicine for the prolonged periods necessary to destroy all vestiges of the TB organism. In New York City, one-third of all TB patients in 1991 had infections resistant to one or more antibiotic drugs.
Bernadine Healy, M.D., director of the National Institutes of Health, said, "This new study is an indication of NIH's strong commitment to an aggressive TB research agenda."
The NIAID study will evaluate the benefits of adding a new drug for tuberculosis treatment, levofloxacin, to the usual four-drug therapy used in geographic areas, including New York, where TB organisms are commonly resistant to one or more anti-TB drugs. Levofloxacin belongs to a class of medications called fluoroquinolones that have demonstrated anti-TB activity in laboratory tests and in preliminary studies in humans.
People who live where drug-resistant TB is not common also can enroll in the trial and will receive the four-drug regimen without levofloxacin. The four-drug regimen uses isoniazid (INH), rifampin, ethambutol and pyrazinamide.
After an eight-week induction phase of therapy using four or five drugs, patients will enter the continuation phase of their treatment, and will receive two or three drugs for an additional 18 to 70 weeks. To determine which candidate continuation therapy a patient receives, study investigators will use laboratory cultures that can identify which drugs are effective against the strain of TB a patient carries. In the continuation phase of therapy:
Participants who carry strains of the TB organism susceptible to the standard drugs will be randomly assigned to receive a two-drug regimen for either an additional 18 or 31 weeks.
Participants with single-drug resistant TB will receive either two- or three-drug regimens, some of which will include levofloxacin. Eligible patients with INH-resistant TB will continue treatment for 44 additional weeks, and those with rifampin-resistant TB, for 70 additional weeks.
Patients with TB strains resistant to multiple drugs will be taken off the study and switched to another, more intensive treatment regimen.
During the continuation phase of treatment, all participants will receive twice-weekly, so-called intermittent therapy rather than daily doses of the drugs. Intermittent therapy previously has been found effective in TB patients without HIV infection.
"A shorter treatment regimen or an effective intermittent regimen would facilitate directly observed therapy, with a clinic or outreach worker watching participants take their study medication," said Dr. Fauci. "Increased compliance with therapy would result in a better cure rate, less TB transmission and fewer opportunities for the TB organisms to develop drug resistance."
The study, known as CPCRA 019/ACTG 222, has an open-label design: both participants and the study investigators know which medications a patient is taking. Patients will be evaluated every two weeks in the induction phase and every 12 weeks in the continuation phase.
Drugs for the study are being provided by Danbury Pharmacal (INH), Tishcon Corporation (Vitamin B6, administered with INH), Marion Merrell Dow Inc. (rifampin), Lederle Laboratories Division of American Cyanamid Company (pyrazinamide and ethambutol), and The R.W. Johnson Pharmaceutical Research Institute, a division of Ortho McNeil Pharmaceutical Corporation (levofloxacin).
NIAID, the lead institute for TB research at the National Institutes of Health, supports more than 50 research projects related to TB, including four other clinical trials for HIV- infected persons. NIH is one of the eight agencies of the U.S. Public Health Service within HHS.
The AIDS Clinical Trials Group, established in 1987, is a nationwide clinical trials network that conducts studies to evaluate the safety and effectiveness of new drugs, drug combinations and vaccines in adults and children at various stages of HIV disease. The ACTG has 61 sites affiliated with major medical centers in 34 U.S. cities.
The Terry Beirn Community Programs for Clinical Research on AIDS involve 17 community-based research programs in 13 U.S. cities, with some 160 affiliated sites. This program includes groups of primary care physicians and nurses who work in community health centers and hospitals, private clinics or practices and drug addiction treatment facilities.
For enrollment information, site location and eligibility requirements for CPCRA 019/ACTG 222 and other AIDS clinical trials, call 1-800-TRIALS-A, Monday through Friday, 9 a.m. to 7 p.m., EST.
For press inquiries only, call Greg Folkers at (301) 402-1663