A daily antituberculosis regimen was more effective and caused less resistance to rifampicin than a thrice-weekly regimen in HIV-positive patients with pulmonary tuberculosis (TB) receiving antiretroviral therapy, according to the results of a study published in JAMA Internal Medicine.

Narendran Gopalan, DNB, DTCD, from the National Institute for Research in Tuberculosis in Chennai, India, and colleagues conducted an open-label clinical trial (ClinicalTrials.gov Identifier: NCT00933790) and randomly assigned 331 HIV-positive adults with newly diagnosed pulmonary TB to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. The part-daily regimen consisted of a daily intensive phase followed by an intermittent continuation phase. The other 2 regimens had a consistent dosing schedule in both the intensive and continuation phases.

The investigators performed clinical and sputum microbiologic monthly examinations of patients until 18 months after randomization. The primary outcome was favorable response, which was defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment.

In patients who received the daily regimen, 91% experienced a favorable response; 80% of patients who received the part-daily regimen had a favorable response, and 77% of patients who received the intermittent regimen experienced a favorable response. A total of 6 patients experienced bacteriologic failure in the intermittent regimen group, and acquired rifampicin resistance (ARR) developed in 4 of these individuals. Treatment failures occurred in 3 patients in the part-daily regimen, but no cases of ARR developed. The daily regimen group had no treatment failures and no cases of ARR.

During therapy, 18 deaths occurred — 4 in the daily group, 9 in the part-daily group, and 5 in the intermittent group. Adverse reactions occurred in 27%, 21%, and 17% of the daily, part-daily, and intermittent regimen groups, respectively. During the intensive phase, 9% of patients who received daily antituberculosis therapy experienced hepatotoxic effects compared with 2% of those who received intermittent therapy. 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 incidence of recurrence did not differ significantly among the groups. Immune reconstitution inflammatory syndrome occurred in 28%, 22%, and 35% of the daily, part-daily, and intermittent regimen groups, respectively.

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The authors concluded that daily administration of antituberculosis therapy was optimal, resulted in higher cure rates, and prevented ARR. The slightly higher hepatotoxicity was manageable under trial conditions.

Reference

Gopalan N, Santhanakrishnan RK, Palaniappan AN, et al. Daily vs intermittent antituberculosis therapy for pulmonary tuberculosis in patients with HIV. A randomized clinical trial [published online March 5, 2018]. JAMA Intern Med. doi:10.1001/jamainternmed.2018.0141