NIAID Study Finds Initial Intermittent Treatment Effective for HIV-Related TB
Combination antibiotic therapy given intermittently (less than daily) is an effective initial treatment for persons with HIV-related tuberculosis (TB), according to an ongoing study funded by the National Institute of Allergy and Infectious Diseases (NIAID).
This preliminary finding should help guide clinicians who treat people co-infected with HIV and TB," says Steven M. Schnittman, M.D., assistant director for clinical research in NIAID's Division of AIDS. "The adoption of earlier intermittent regimens could facilitate the treatment of these patients in directly observed TB therapy, with a clinic or outreach worker watching participants taking their study medication."
Although initial intermittent TB therapy is known to be effective in non-HIV-infected patients, its efficacy has not been proven in patients with HIV-related TB. Many clinicians, therefore, continue to prescribe daily multidrug therapy for several months for these patients, before switching to intermittent therapy for the remainder of a typical nine-month course of treatment.
In the NIAID multicenter clinical trial, 114 patients with HIV-related TB received directly observed, multidrug antibiotic therapy during an eight-week induction, or treatment initiation, phase. Patients in each of two groups received four standard anti-TB drugs: isoniazid, rifampin, pyrazinamide and ethambutol. One group also received levofloxacin, an experimental anti-TB drug. The drugs were given daily for only the first two weeks, then three times a week for the six weeks remaining in the induction period. The four-drug and five-drug regimens were equally effective -- at the end of eight weeks, sputum specimens from more than 95 percent of patients in each group tested negative for the presence of TB bacteria.
This is perhaps the first strong evidence that a largely intermittent induction schedule of directly observed, multidrug therapy is a very effective treatment for HIV-related TB, as measured by sputum culture response," says Wafaa El-Sadr, M.D., of the Harlem Hospital Center in New York. Dr. El-Sadr will present the interim results of the ongoing study today at the XIth International Conference on AIDS in Vancouver, British Columbia.
Dr. El-Sadr notes that a large part of the recent global increase in TB cases is due to the growing number of persons who are infected with both HIV and TB. HIV infection increases the chance that dormant TB infection will become activated. The progression of TB disease also is accelerated in persons with HIV infection. The greater convenience of intermittent TB therapy could have a major impact on the management of TB worldwide, she says.
An effective intermittent regimen should increase rates of compliance with therapy, particularly for patients receiving directly observed therapy, because they will not have to come to the clinic as frequently to receive their medication," says Dr. El-Sadr. "Increased compliance with therapy would result in a better cure rate, less TB transmission and fewer opportunities for the TB organism to develop drug resistance."
In a continuation of the study, Dr. El-Sadr and her collaborators in the NIAID-funded Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and AIDS Clinical Trials Group (ACTG), will assess the effectiveness of various combinations of anti-TB agents administered for different durations following the two-month induction phase.
The CPCRA is a network of primary care physicians and nurses who work with NIAID staff to design and conduct community-based clinical trials in patients with HIV disease and AIDS. NIAID currently funds 16 CPCRA units in 15 cities throughout the United States. The ACTG 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 includes 30 Adult and 22 Pediatric Units at academic institutions and medical centers in 20 states, the District of Columbia and Puerto Rico.
NIAID is a component of the National Institutes of Health(NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.
NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page. The address is http://www.niaid.nih.gov.