The study, sponsored by the National Institute of Allergy and
Infectious Diseases (NIAID), the Centers for Disease Control and
Prevention (CDC), and the Pan American Health Organization
(PAHO), holds promise for reducing HIV-related TB disease and
death in the United States and throughout the world.
"This is an important finding that could have a very positive
impact on the health of persons infected with both HIV and TB," says
NIAID Director Anthony S. Fauci, M.D. "TB and HIV are synergistic
infections -- HIV infection speeds the progression of TB disease and
increases the rate of activation of latent TB infection. TB appears to
increase HIV replication in HIV-infected individuals." The World
Health Organization (WHO) estimates that more than 5 million people
worldwide are co-infected with HIV and TB, and approximately one-
third of all HIV-related deaths worldwide are caused by TB.
Study Chair Fred Gordin, M.D., of the Veterans Affairs Medical
Center in Washington, D.C., presented preliminary results of the
short-course prevention study last week at the 5th Conference on
Retroviruses and Opportunistic Infections in Chicago, Ill. He also will
present the findings at a meeting of TB researchers scheduled for
Feb. 18-20, 1998, at WHO headquarters in Geneva, Switzerland.
Nearly 1,600 HIV-infected people participated in the study, a
randomized trial comparing two months of daily rifampin (RIF) and
pyrazinamide (PZA) with 12 months of daily isoniazid (INH). More
than 70 percent of the participants were from the United States,
enrolled throughout the country at 53 different sites sponsored by
NIAID's Terry Beirn Community Programs for Clinical Research on
AIDS (CPCRA) and Adult AIDS Clinical Trials Group (ACTG), and the
CDC. Other participants were enrolled at CDC sites in Haiti and
Brazil, and a site in Mexico sponsored by PAHO through an
agreement with Mexico's Ministry of Health and National Institute of
All participants had positive TB skin tests, indicating that they
harbored inactive TB bacteria. Analysis of study data showed that
after an average of 36 months of follow-up, the number of TB cases
was the same in each treatment group. Fewer deaths occurred
among patients in the two-drug arm than in the one-drug arm, but the
difference was not statistically significant. Importantly, however,
compliance with treatment was significantly better in the two-drug arm
-- 80 percent of individuals in the RIF/PZA group completed their
treatment, while less than half of the individuals in the INH group
completed the year-long regimen.
"We know that 12 months of INH can prevent TB disease in
people with HIV, but poor compliance limits the effectiveness of this
regimen," explains Dr. Gordin, principal investigator at NIAID's
CPCRA Unit in Washington, D.C. In most clinical settings, he says,
compliance rates for patients receiving INH to prevent disease
typically are lower than were seen in this study.
"In addition to improving treatment compliance, the short-course
regimen could greatly reduce the cost of TB prevention
programs," adds Dr. Gordin, who notes that personnel and
administrative costs make running a 12-month, daily treatment
program very expensive. Although RIF and PZA are more expensive
than INH, Dr. Gordin says implementing the two-drug short-course
regimen likely would be far less expensive and thus an attractive
alternative to INH-based TB prevention programs. The prospect of
less costly TB prophylaxis may also make such programs
economically feasible in countries that cannot afford INH-based
"Certainly, the greatest impact of these findings will be in the
United States and other countries where preventive therapy is widely
recommended for individuals infected with TB and at risk for
developing active disease," notes Helene Gayle, M.D., director of the
CDC's National Center for HIV, STD and TB Prevention. "But as the
role of preventive therapy continues to evolve in the developing world,
this short-course regimen may help extend the reach of therapy
in certain high-risk groups, including HIV-infected individuals
and children living in households with people with infectious TB."
Dr. Gayle adds that although preventive therapy for infected
individuals in these high-risk groups can play a role in TB control
efforts in developing nations, the primary focus of efforts in areas
with limited resources should remain the diagnosis and treatment of active
cases of TB disease.
Although this study included only HIV-infected persons, Dr.
Gordin notes that the short course RIF/PZA regimen also should be
useful for preventing active TB in persons without HIV who have
latent TB infection. The CDC currently recommends six to 12 months
of daily INH prophylactic therapy for people with a positive TB skin
test who are at increased risk for developing active TB. These
include: people in close contact with a person who has active TB
disease; people who became infected with TB bacteria in the last two
years; babies and young children; people who inject drugs; people
who have weakened immune systems; and elderly people. The
results of this study will provide important information for new
recommendations on tuberculosis preventive therapy to be issued by
CDC later this year.
NIAID, part of the National Institutes of Health (NIH), supports
biomedical research to prevent, diagnose and treat illnesses such as
AIDS, tuberculosis, malaria, asthma and allergies. CDC is the
nation's lead agency for the prevention and control of tuberculosis
and other diseases. NIH and CDC are agencies of the U.S.
Department of Health and Human Services.
PAHO is an international public health agency with more than
90 years of experience in working to improve health and living
standards of the countries of the Americas. It serves as the
specialized organization for health of the Inter-American System. It
also serves as the Regional Office for the Americas of the World
Health Organization and enjoys international recognition as part of the
United Nations system.
Press releases, fact sheets and other NIAID-related materials are
available via the NIAID Web site at http://www.niaid.nih.gov.