Daily Antituberculosis Therapy Superior for Pulmonary TB in PLWH
APRIL 27, 2018
Elizabeth Kukielka, PharmD
Narendran Gopalan, DNB, DTCDWorldwide, tuberculosis (TB) remains the leading cause of morbidity and mortality for patients living with HIV (PLWH). As of 2009, the World Health Organization (WHO) recommended daily antituberculosis therapy (ATT) for TB in PLWH, while the standard of care in India at the time was intermittent, or thrice-weekly, ATT in those patients.
An additional cause for concern in selecting appropriate ATT in PLWH in 2009 was the development of acquired rifampicin resistance (ARR), which complicates treatment. Although ARR is rare in HIV-negative patients, it has been observed in PLWH with TB who are undergoing intermittent ATT (once-, twice-, or thrice-weekly regimens).
Without any data available for the head-to-head comparisons of the 2 regimens, the superiority of 1 regimen over the other was unclear. Narendran Gopalan, DNB, DTCD, of the National Institute for Research in Tuberculosis (NIRT) in Chennai, India, led a study that investigated the efficacy of these treatment regimens in achieving a cure for TB and preventing ARR.
The study took place at several NIRT centers in southern India from 2009 to 2016. Interim analyses were planned for when outcomes were available for 33%, 66%, and 100% of patients.
Patients were randomized to receive ATT either daily through the entire study; part-daily, defined as daily therapy during an intensive period followed by intermittent therapy; or intermittent, defined as thrice-weekly, through the entire study. The primary study outcome was the proportion of patients achieving a favorable response at the completion of ATT, defined as the completion of the course of treatment and negative sputum cultures.
Patients were included in this study if they were 18 years or older with HIV and newly diagnosed pulmonary TB. Patients were excluded if they were pregnant or breastfeeding, taking a protease inhibitor-based ART regimen, had known hypersensitivity or resistance to rifampicin, had a serious psychiatric illness, had significant hepatic or renal dysfunction at baseline, or were near death.
By the second interim analysis, when 331 patients had been enrolled and allocated to therapy, the trial was halted due to clear superiority of the daily regimen. In the modified intent-to-treat analysis, favorable responses were observed in 89 of 98 patients (91%), 77 of 96 patients (80%), and 75 of 98 patients (77%) in the daily, part-daily, and intermittent regimens, respectively, with the difference between the daily and intermittent regimens reaching statistical significance.
There were no treatment failures in the daily group, while 8 patients in the intermittent group and 3 patients in the part-daily group experienced treatment failures. No patients in the daily or part-daily groups experienced ARR, while 4 patients in the intermittent group experienced ARR.
In terms of safety, toxic effects were statistically similar among treatment groups, but patients in the daily group did experience a higher incidence of hepatotoxicity. The hepatotoxicity was successfully managed, and the original, unmodified treatment was resumed in all but 2 patients.
Gopalan and colleagues concluded, “A daily ATT regimen for 6 months in HIV-positive patients with TB receiving concomitant ART proved superior to an intermittent regimen in terms of efficacy and prevention of ARR.”
The study, “Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV,” was published in JAMA Internal Medicine.