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Clinical Trial
. 2019 Mar 14;380(11):1001-1011.
doi: 10.1056/NEJMoa1806808.

One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis

Susan Swindells  1 , Ritesh Ramchandani  1 , Amita Gupta  1 , Constance A Benson  1 , Jorge Leon-Cruz  1 , Noluthando Mwelase  1 , Marc A Jean Juste  1 , Javier R Lama  1 , Javier Valencia  1 , Ayotunde Omoz-Oarhe  1 , Khuanchai Supparatpinyo  1 , Gaerolwe Masheto  1 , Lerato Mohapi  1 , Rodrigo O da Silva Escada  1 , Sajeeda Mawlana  1 , Peter Banda  1 , Patrice Severe  1 , James Hakim  1 , Cecilia Kanyama  1 , Deborah Langat  1 , Laura Moran  1 , Janet Andersen  1 , Courtney V Fletcher  1 , Eric Nuermberger  1 , Richard E Chaisson  1 ; BRIEF TB/A5279 Study Team
Collaborators, Affiliations
Clinical Trial

One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis

Susan Swindells et al. N Engl J Med. .

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. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).

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Figures

Figure 1.
Figure 1.
Enrollment and Follow-up.
Figure 2.
Figure 2.. Kaplan–Meier Analysis of the Primary End Point.
Shown are the percentages of patients who were free from the primary end point — the diagnosis of tuberculosis or death from tuberculosis or an unknown cause — among all the patients (Panel A), among those with a CD4+ count of 250 cells per cubic millimeter or less (Panel B), and among those with a CD4+ count of more than 250 cells (Panel C), according to the receipt of either a 1-month regimen of daily rifapentine plus isoniazid (1-month group) or 9 months of isoniazid alone (9-month group).
See this image and copyright information in PMC

Comment in

References

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    1. Golub JE, Cohn S, Saraceni V, et al. Long-term protection from isoniazid preventive therapy for tuberculosis in HIV infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study. Clin Infect Dis 2015; 60: 639–45. - PMC - PubMed

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