Daily TB Therapy Superior to Thrice-Weekly in Patients with HIV

A recent study has shown that daily antituberculosis therapy (ATT) is more effective than a thrice-weekly regimen among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy. Daily treatment is also associated with a lower incidence of acquired rifampicin resistance (ARR).

Narendran Gopalan, DNB, DTCD, from the National Institute for Research in Tuberculosis in Chennai, India, and colleagues published the results of their randomized clinical trial online March 5, 2018 in JAMA Internal Medicine.

Among individuals who are HIV-positive—including those receiving antiretroviral treatment—tuberculosis is the most common presenting illness and the most common cause of death.

However, the benefit of using daily over thrice-weekly ATT for pulmonary TB among HIV-positive patients who are receiving antiretroviral therapy has been unclear.

“This study addresses the vital issue of optimal frequency of anti-TB drug administration among HIV-positive patients with TB by comparing the efficacy of daily, part-daily, and intermittent ATT regimens in a pure group of patients newly diagnosed with culture-positive, rifampicin-sensitive, pulmonary TB,” the authors write.

In their study, Dr. Gopalan and colleagues randomized 331 HIV-positive adults with newly-diagnosed pulmonary TB to receive daily, part-daily, or intermittent ATT regimens.

The daily regimen involved daily treatment during both the intensive and continuation phases. In contrast, the part-daily regimen consisted of a daily intensive phase followed by an intermittent continuation phase. And, the intermittent regimen involved thrice-weekly treatment throughout the study.

According to the authors, the efficacy of the daily regimen was superior to that of the other 2 regimens. Favorable treatment responses occurred in 91% of patients receiving the daily regimen, compared with in 80% of those receiving the part-daily regimen, and in 77% of those receiving the intermittent (thrice-weekly) regimen.

The authors define a favorable response as “treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment.”

The authors also found also that ARR developed only in 4 patients receiving the intermittent regimen. This led the data safety monitoring committee to halt the study at the stage of second interim analysis, they say, after 6 months of treatment.

The authors note that adverse reactions occurred more commonly in patients receiving daily treatment (27%), compared with in those receiving part-daily (21%) or intermittent (17%) treatment. In particular, during the intensive phase of the ATT regimens, 9% of patients receiving daily treatment developed hepatotoxic effects, compared with just 2% of those receiving intermittent treatment.

“However, all cases of jaundice resolved by 28 days in the daily and part-daily regimen groups and by 20 days in the intermittent regimen group,” the authors emphasize.

A total of 18 patients died during the study—4 in the daily group, 9 in the part-daily group, and 5 in the intermittent group.

The incidence of TB recurrence was similar among all 3 groups during 1-year follow up.

“Daily administration of antituberculosis therapy resulted in higher cure rates and prevented acquired rifampicin resistance compared with a thrice-weekly regimen, but with slightly higher hepatotoxicity, which was manageable under trial conditions,” the authors conclude.

They also stress that these findings support those of a recent meta-analysis among HIV-positive patients with TB that demonstrated a significantly greater odds of treatment failure and ARR in patients receiving intermittent ATT than in those receiving a daily regimen.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.