For prevention of tuberculosis (TB) in people with HIV, a single month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone, according to study data published in The New England Journal of Medicine.
A randomized open-label phase 3 noninferiority 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 (ClinicalTrials.gov, NCT01404312). The study enrolled 3000 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 millimeter 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.
Researchers concluded that 1 month of daily rifapentine plus isoniazid was noninferior to the 9 months of isoniazid regimen for preventing tuberculosis in high-risk patients with HIV infection.
Swindells S, Ramchandani R, Gupta A, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380:1001-1011.