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TB Notes 4, 2002
Update from the Research and Evaluation Branch
Update on Study 22
The major report from TB Trials Consortium (TBTC) Study 22 was
published in the August 17 edition of The Lancet.
The article presents the findings from the HIV-negative arm of this
important trial,1 which evaluated a regimen of once-weekly
isoniazid and rifapentine given during the continuation phase of
therapy (from week 9 to week 24 of treatment), as an alternative
to the standard twice-weekly regimen of isoniazid and rifampin.
TBTC investigators found the once-weekly regimen to be safe and
effective for HIV-negative patients without signs of advanced TB
(i.e., those with no lung cavitation identifiable on chest x-ray).
Study 22 enrolled 1,004 HIV-negative patients with active TB disease
who had completed 8 weeks of intensive TB therapy with the four
frontline TB drugs – isoniazid, rifampin, pyrazinamide, and ethambutol.
Enrolling sites were located in New York City, NY; Newark, NJ; Baltimore,
MD; Atlanta, GA; San Diego, CA; Los Angeles, CA; Phoenix, AZ; Chicago,
IL; Fort Worth, TX; Winnipeg, Canada; Denver, CO; Washington, DC;
Durham, NC; Miami, FL; Little Rock, AR; Hines, IL; Houston, TX;
San Antonio, TX; San Francisco, CA; Charlotte, NC; and Nashville,
TN. Patients were randomly assigned to one of two groups during
the 16-week continuation phase of TB treatment. One trial group
received once-weekly isoniazid and rifapentine, the first new TB-specific
drug approved by the Food and Drug Administration in 30 years. The
other group received the standard therapy of twice-weekly isoniazid
Both groups of patients were then followed for 2 years. Forty-six
(9.2%) patients who took the once-a-week regimen either relapsed
or experienced treatment failure. Twenty-eight (5.6%) patients who
took the twice-weekly regimen relapsed or had a treatment failure.
In a life table analysis, these rates were 10.3% and 5.9%, respectively.
In a proportional hazards regression model, which adjusted for imbalances
in key risk factors at enrollment, five factors were significantly
associated with risk of failure or relapse: 1) positive sputum culture
at 2 months, 2) cavitation on chest x-ray, 3) being more than 10%
underweight at diagnosis, 4) having bilateral disease on chest x-ray,
and 5) being of white race/ethnicity. The difference between treatment
arms was not statistically significant in this regression analysis.
Importantly, the rates of failure or relapse among patients with
no cavitation on x-ray were quite similar in the two treatment arms
(2.9% vs. 2.5%, respectively). Mortality and toxicity were similar
in the two groups. The study investigators concluded that the once-weekly
regimen was not as efficacious as the twice-weekly regimen, but
that the once-weekly isoniazid and rifapentine regimen performed
well in HIV-negative TB patients who did not have cavitation on
chest x-ray. These investigators recommend that this regimen be
considered for use in such patients. Revised ATS/CDC treatment recommendations
are expected to appear in late 2002, and will address the use of
Since the once-weekly isoniazid and rifapentine regimen is administered
less frequently than the standard regimen, costs associated with
directly observed therapy are diminished,2 and adherence
may be improved, helping to cure more HIV-negative TB patients and
prevent further TB transmission. The once-weekly regimen is not
recommended for HIV-infected TB patients. CDC is interested in learning
of programmatic experience with this regimen in appropriately selected
HIV-negative TB patients.
—Reported by Andrew Vernon, MD, MHS
Div of TB Elimination
Findings from the HIV-positive arm were published in Lancet
in 1999 (Vernon A, Burman W, Benator D, Khan A, Bozeman L. Relapse
with rifamycin mono-resistant tuberculosis in HIV-infected patients
treated with supervised once-weekly rifapentine and isoniazid.
Taylor Z, Qualls N, Vernon A, Villarino E, O'Brien R. A prevention
effectiveness study of rifapentine in the continuation phase of
therapy for active pulmonary tuberculosis. Abstract. Am J Respir
Crit Care Med 2000; 161: A524.
Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination - http://www.cdc.gov/tb
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