Rifapentine plus isoniazid non-inferior to isoniazid in HIV related TB

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For prevention of tuberculosis (TB) in people with HIV, a single month regimen of rifapentine plus isoniazid was non-inferior to 9 months of isoniazid alone, according to study data.

A randomised open-label phase 3 non-inferiority trial was used to compare the efficacy and safety of the 2 treatment courses in patients with HIV who were living in areas of high TB prevalence or had evidence of latent TB infection.

The BRIEF TB/A5279 Study enrolled 3,000 patients, 54% of whom were women, and followed them for a median of 3.3 years. The median CD4+ count of the study group was 470 cells per cubic millimetre and half were receiving antiretroviral therapy. Roughly 50% of the patients were receiving antiretroviral therapy at entry and 77% of these patients had an undetectable HIV viral load.

The primary study end point was a first diagnosis of TB or death related to tuberculin infection or an unknown cause. This end point occurred in 2% of the 1488 patients receiving the 1-month regimen and 2% of the 1498 patients receiving the 9-month treatment course, resulting in incidence rates of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, −0.02 per 100 person years; upper limit of the 95% CI, 0.30). The percentage of treatment completion in the 1-month group was significantly higher compared with the standard 9-month course: 97% vs 90%, respectively (P <.001). Severe adverse events occurred in 6% and 7% of the 1-month and 9-month groups, respectively (P =.07).

Study limitations included the exclusion of adults who were pregnant or breastfeeding and individuals aged younger than 13 years with HIV infection. Also, the overall TB incidence was lower than expected, which limited the ability of researchers to evaluate in subgroups with precision.

The study investigators also noted that some assumptions made were not based on recent evidence showing an independent benefit from antiretroviral therapy in preventing TB.

Half of the patients in this study were receiving antiretroviral therapy at the beginning of the study and this increased to 90% by the end. Previous work found that co-administration of rifapentine and isoniazid with efavirenz did not adversely affect efavirenz concentrations, but future studies are required to investigate more contemporary antiretroviral drugs.

Abstract
Background: Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates.
Methods: We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25.
Results: A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, −0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P=0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001).
Conclusions: A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group.

Authors
Susan Swindells, Ritesh Ramchandani, Amita Gupta, Constance A Benson, Jorge Leon-Cruz, Noluthando Mwelase, Marc A Jean Juste, Javier R Lama, Javier Valencia, Ayotunde Omoz-Oarhe, Khuanchai Supparatpinyo, Gaerolwe Masheto, Lerato Mohapi, Rodrigo O da Silva Escada, Sajeeda Mawlana, Peter Banda, Patrice Severe, James Hakim, Cecilia Kanyama, Deborah Langat, Laura Moran, Janet Andersen, Courtney V Fletcher, Eric Nuermberger, Richard E Chaisson

Infectious Disease Advisor report
New England Journal of Medicine abstract


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