Shorter treatment for latent TB effective, recommended by CDC

Latent tuberculosis (TB) infection can be effectively treated with just a few months of therapy, according to a new study and updated recommendations from the CDC. However, commonly used tests for the disease have a high rate of false positives, according to another study published last week.

The treatment study was an open-label, noninferiority trial in which patients at high risk for TB (most had close contact with a TB patient and positive skin tests) who lived in the U.S., Canada, Brazil or Spain were randomized to either nine months of self-administered daily isoniazid (300 mg) or three months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg). Each group had almost 4,000 subjects and they were followed for 33 months for the development of confirmed tuberculosis. The results appeared in the Dec. 8 New England Journal of Medicine.

In a modified intention-to-treat analysis, researchers found that the shorter, combined therapy was as effective as the isoniazid-alone regimen; tuberculosis developed in 7 (or 0.19%) of the combination-therapy group compared to 15 (or 0.43%) of the isoniazid group. The combined group was also more likely to complete treatment: 82.1% vs. 69.0% (P<0.001). However, despite having lower rates of hepatotoxicity (0.4% vs. 2.7%), participants in the combination group were more likely to discontinue therapy due to an adverse event (4.9% vs. 3.7%; P=0.009).

The study authors noted that the higher rate of adverse-event-related discontinuation could be due to more frequent interactions with study clinicians during the directly observed therapy. The direct observation, along with the shorter duration of treatment, also probably explains the higher completion rate in the combined group than the isoniazid group. They concluded that the combination regimen could be used effectively in settings such as the studied ones, although additional safety monitoring should be conducted. An accompanying editorial called for more research into the duration of protection for patients against TB from this regimen, particularly in high-incidence settings and among HIV-positive patients.

Based on the results of the study, the CDC added a new treatment option to their recommendations for latent TB: 12 once-weekly doses of rifapentine and isoniazid taken under the supervision of a health care worker. The regimen is recommended for otherwise healthy people aged 12 and older who have had recent exposure to contagious TB, conversion from negative to positive on a test for TB, or a chest X-ray indicating prior TB disease. Patients with HIV who are otherwise healthy and not taking antiretrovirals may also use this regimen. The regimen is not recommended for use among children under 2, women who are pregnant or planning to become pregnant, and HIV-infected people taking antiretrovirals. Patients on the regimen should be monitored for possible adverse effects and undergo a clinical assessment at least monthly, the CDC said.

In the second study, researchers tested about 2,000 U.S. Army recruits in South Carolina for TB. Each recruit completed a risk-factor questionnaire and underwent the tuberculin skin test (TST) and two interferon gamma release assays (IGRAs): the QuantiFERON-TB Gold In-Tube test and the TSPOT TB test. The study found that the specificities of the tests were not significantly different, at least in this low-risk population, even though the IGRAs were designed to increase specificity.

Of the 88 subjects with a positive test, only 10 (11.4%) were positive on all three tests. Twenty of the subjects (22.7%) were positive on two tests. Based on the results, the researchers concluded that in a low-prevalence population, most positive results from any of the tests would be false positives. The findings support the use of risk stratification to guide interpretation of both TSTs and IGRAs, and the CDC's recommendation not to target low-risk people for testing, the authors concluded. The study was published early online by the American Journal of Respiratory and Critical Care Medicine on Dec. 9.