Shorter weekly course of rifapentine-isoniazid associated with much higher treatment completion rates compared to longer daily course

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   

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1. Shorter weekly course of rifapentine-isoniazid associated with much higher treatment completion rates compared to longer daily course

Abstract: https://www.acpjournals.org/doi/10.7326/M20-7577    

Editorial: https://www.acpjournals.org/doi/10.7326/M21-3170

A randomized trial found that treatment completion was higher among persons with HIV infection who were assigned a shorter course of rifapentine-isoniazid therapy to prevent tuberculosis disease compared to those taking a longer course. A second round of treatment provided no additional protection from developing tuberculosis disease in high-transmission areas. The findings are published in Annals of Internal Medicine.

Tuberculosis preventive therapy for persons with HIV is effective, but its durability is uncertain. In the WHIP3TB trial (Weekly High Dose Isoniazid and rifapentine [P] Periodic Prophylaxis for TB trial), researchers from the Aurum Institute, Houghton, South Africa, hypothesized that, among persons with HIV receiving antiretroviral therapy, treatment completion of weekly rifapentine and isoniazid for 3 months would be superior to 6 months of daily isoniazid, and that annual weekly rifapentine and isoniazid for 3 months would be more effective than a single round.

The researchers randomly assigned 4,014 persons with HIV who were receiving antiretroviral therapy and did not have active tuberculosis to receive weekly rifapentine–isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24. Treatment completion rates as well as the effectiveness of the different regimens were compared. The researchers found that tuberculosis preventive therapy with short-course, weekly rifapentine and isoniazid for 3 months was associated with much higher treatment completion rates compared with standard daily isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of short-course tuberculosis preventive therapy one year later did not provide additional benefit.

Media contacts For an embargoed PDF, please contact Angela Collom at [email protected]. To speak with the corresponding author, Gavin Churchyard, MBBCh, PhD, please contact Kanya Ndaki at [email protected].  

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2. Simple donor-specific biomarker predicts liver transplant rejection independent of recipient

Abstract: https://www.acpjournals.org/doi/10.7326/M20-7957     

URL goes live when the embargo lifts

A cohort study found that class I HLA evolutionary divergence (HED) of the donor predicts acute or chronic rejection of a liver transplant. This prognostic marker can be found rapidly at no additional cost and has the potential to orientate donor selection and guide immunosuppression following transplantation. The findings are published in Annals of Internal Medicine.

Organ rejection depends on HLA proteins expressed by donor’s and recipient’s cells which are variable between individuals and thus are different between donors and recipients. Compatibility means that the more the HLA proteins are similar between donor and recipient, the less likely the organ is to be rejected. The HED, a continuous metric quantifying the peptidic differences between 2 homologous HLA alleles, reflects the breadth of the immunopeptidome presented to or by the immune cells.

Researchers from the Assistance Publique, Hôpitaux de Paris, (France) studied health records for 1,154 adults and 113 children who had a liver transplant between 2004 and 2018 to assess the potential effect of donor or recipient HED on liver transplant rejection. They found that HED calculated from the HLA alleles of the donor, had a much stronger influence on liver transplant success than HLA compatibility. The higher the HED of a donor of liver graft, the more frequent rejection and this was completely independent of the HLA compatibility of donors and recipients. These findings suggest for the first time that a donor-dependent biomarker (independent of the recipient) can predict allograft rejection. This finding has significant implications in clinical practice.