Prophylactic antivirals prevent chronic HCV in patients receiving kidneys from positive donors

September 07, 2020

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.

1. Prophylactic antivirals prevent chronic hepatitis C in patients receiving kidneys from positive donors


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Prophylactic treatment with direct-acting antivirals (DAAs) prevented chronic hepatitis C virus (HCV) infection in 10 patients receiving kidneys from HCV positive deceased donors. This approach has potential to help shorten waiting times on the organ waitlist. A brief research report is published in Annals of Internal Medicine.

Kidneys from deceased donors with HCV are increasingly available, yet hundreds are discarded annually because of a limited number of HCV-viremic candidates. An innovative strategy of transplanting kidneys from HCV-positive donors to HCV-negative recipients (HCV D+/R-) by using DAAs has shown early success, but the optimal timing and duration of DAA therapy remain unclear.

In the REHANNA (Renal Transplants in Hepatitis C Negative Recipients With RNA Positive Donors) clinical trial, researchers from Johns Hopkins School of Medicine investigated outcomes with 4-week prophylaxis with the pan-genotypic combination of glecaprevir and pibrentasvir (G/P). Eligible candidates had HCV antibody and RNA negativity, were on the deceased-donor kidney transplant waitlist, and did not have HIV, active hepatitis B virus, or liver disease. Participants received 1 G/P dose before organ perfusion, then 1 dose daily for 4 weeks. HCV RNA was measured on postoperative days 1 and 4; prophylaxis weeks 1, 2, and 4; and post-prophylaxis follow-up weeks 1, 4, 8, and 12. The researchers found that in all 10 cases where a patient received a kidney from an HCV-positive donor, 4-week G/P prophylaxis prevented HCV without treatment-related adverse events or substantial liver enzyme abnormalities.

Media contacts: For an embargoed PDF, please contact Lauren Evans at To reach the corresponding author, Christine Durand, MD, please contact Michael Newman at

2. Rising cost may be a barrier to widespread use of HIV PrEP

Cost of PrEP increased an average of 5% each year between 2014 and 2018



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A retrospective cohort study found that cost may be a key factor in preventing more widespread use of HIV preexposure prophylaxis (PrEP). National expenditures on tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP increased nearly 20-fold from $114 million in 2014 to $2.08 billion in 2018. In 2018, 204,270 patients used PrEP, representing only 18 percent of those with an indication for PrEP receiving it. The findings are published in Annals of Internal Medicine.

Although PrEP is highly effective, is recommended by the Centers for Disease Control and Prevention (CDC) and U.S. Preventive Services Task Force (USPSTF), and is a key component of the federal government's Ending the HIV Epidemic plan, only a fraction of persons who could benefit from PrEP receive it.

Researchers from the CDC used data from a large national pharmacy database to estimate out-of-pocket (OOP) and third-party payments for PrEP. They found that the cost increased an average of 5 percent each year between 2014 and 2018 from $1,350 to $1,638 for a month supply. At least $2 billion was spent on PrEP medication costs in the US in 2018, and this accounted for PrEP coverage of 18 percent of persons with an indication for PrEP. Expanding PrEP use is needed to reach the Ending the HIV Epidemic goal of 50 percent of persons with an indication for PrEP using it. According to the study authors, the overall health care cost of PrEP will likely increase as more persons gain access to and continue to use PrEP. Action to lower PrEP costs can prevent coverage denials, eliminate prior authorizations, and increase access.

Media contacts: For an embargoed PDF, please contact Lauren Evans at To reach the corresponding author, Nathan W. Furukawa, MD, MPH, please contact him directly at

3. New guidelines focus on the diagnosis and management of hereditary hemorrhagic telangiectasia


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Hereditary hemorrhagic telangiectasia (HHT) is a rare and underdiagnosed bleeding disorder that affects the blood vessels, and may result in chronic bleeding, acute hemorrhage, and complications from shunting through vascular malformations characteristic of the disease. A diagnosis of HHT allows appropriate screening and preventive treatment to be undertaken in a patient and their affected family members. The Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia are published in Annals of Internal Medicine.

The goal of the Second International HHT Guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT, prevention of HHT-related complications, and treatment of symptomatic disease in areas not previously addressed by guidelines and those where significant new literature had been published. Several other recommendations from the first International HHT Guidelines were not reassessed during this process and remain currently recommended.

The new guidelines cover a broad range of symptoms and make multiple recommendations for addressing each, taking individual patient response into consideration. Symptom areas include epistaxis, gastrointestinal (GI) bleeding, anemia and anticoagulation, and liver vascular malformations. The guidelines also make recommendations regarding pediatric care and pregnancy and delivery. The Guidelines address the use of first-line therapies for chronic bleeding and anemia in HHT and for liver vascular malformations, but also, for the first time, address the role for novel anti-angiogenic therapies in HHT. These Guidelines bring continuity of care through pregnancy, delivery and the pediatric years, with comprehensive recommendations for HHT diagnosis and for screening for lung and brain arteriovenous malformations.

Media contacts: For an embargoed PDF, please contact Lauren Evans at To reach the corresponding author, Marie E. Faughnan, MD, MSc, please contact her directly at

4. Researchers identify a novel histiocytosis with synovial and skin involvement


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Researchers from San Raffaele Scientific Institute, Milan, Italy describe the case of a novel Langerhans-related histiocytosis whose clinical, histopathologic, and genetic features differ from those of any other histiocytic disorder. Their case is published in Annals of Internal Medicine.

Histiocytoses are rare disorders characterized by tissue infiltration by macrophages, dendritic cells, or monocytederived cells. Different subtypes have been described, which collectively encompass a wide range of clinical manifestations from mild to disseminated or life-threatening forms. Classifications of histiocytoisis include Langerhans-related, cutaneous or mucocutaneous, and malignant histiocytoses; Rosai-Dorfman disease; and hemophagocytic lymphohistiocytosis.

This novel Langerhans-related histiocytosis was identified in a 43-year-old patient with debilitating knee pain and inflammation (synovitis) that did not respond to treatment. Her other joints were involved, as well, and multiple nodular skin lesions were present on her face, trunk, and limbs. Laboratory tests showed elevated C-reactive protein levels and erythrocyte sedimentation rate, mild hypernatremia consistent with diabetes insipidus, and elevated serum levels of proinflammatory cytokines. While this clinical picture differed significantly from typical histiocytosis, the researchers studied the skin lesions and found gene representation suggesting histiocytosis, as well as a novel KRAS mutation in myeloid cells. As such, treatment with cobimetinib resolved her symptoms and she remained symptom-free one year later.

Media contacts: For an embargoed PDF, please contact Lauren Evans at To reach the corresponding author, Giulio Cavalli, MD, please contact Nicola Quadri at or Gea Gardini at
Also in this issue:

Time Out Before Talking: Communication as a Medical Procedure
Ideas & Opinions

Graphic Medicine

American College of Physicians

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