DAAs Enable HCV-Infected Heart, Lung Transplants
MAY 13, 2019
Kenneth Bender, PharmD, MA
Ann Woolley, MD, MPH
The trial expands on earlier studies with kidney and liver transplantation from infected donors, which suggest the feasibility of treatment of HCV infection early after transplantation. This trial was conducted in the initiative, DONTATE HCV, an acronym for Donors of Hepatitis C NAT (nucleic acid amplification test) Positive Thoracic Allografts for Transplantation Evaluation in Non-HCV Recipients.
Ann Woolley, MD, MPH, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston MA, and colleagues argue that DAA treatment of HCV contracted from transplantation of infected heart or lung can allow expansion of a currently inadequate organ donor pool.
"Although organ transplantation has increased by 20% during the past 5 years—largely because of an increase in the number of available donors who have died from a drug overdose—many organs that are otherwise medically suitable for transplantation have not been used because of HCV infection in the donors," Woolley and colleagues explained.
In an accompanying editorial, Emily Blumberg, MD, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, pointed out additional advantages of employing DAA treatment to facilitate HCV-mismatched transplantation.
"These donors are typically younger than donors without HCV infection, and they have fewer coexisting conditions that are associated with decreased recipient and organ survival," Blumberg observed.
"Moreover, a sustained viral response (SVR) and cure are now achievable with the increased availability of DAAs, which have expanded efficacy against diverse HCV genotypes, favorable safety profiles, limited drug interactions, and pharmacokinetic properties that allow for administration of these agents irrespective of the patient's renal function," she added.
Woolley and colleagues administered sofosbuvir 400mg/velpatasvir 100mg within hours after transplantation and continued once daily for 4 weeks. The regimen was selected for pangenotypic efficacy as well as for lack of interaction with the immunosuppressive regimens. They reasoned that immediate initiation of a shorter—and less expensive—regimen than the customary 12 weeks employed for chronic infection would be efficacious for exposure to a low viral load that is analogous to requirement for post-exposure prophylaxis.
"This type of transplantation differs from liver transplantation because the heart and lungs are not reservoirs for HCV," the investigators pointed out.
After obtaining a new drug exemption for this treatment plan from the FDA, the investigators recruited 44 patients awaiting organ transplant to participate in the open-label trial. After transplantation, a detectable HCV load was identified in 42 of the 44 (95%), with a median of 1800 IU/ml. HCV genotype 1 was conveyed to 61% of the recipients, genotype 2 to 17%, genotype 3 to 17 %, and 5% received HCV of an indeterminate genotype.
Woolley and colleagues reported that, for the 35 patients who completed 6 months of follow-up, all (100%) maintained excellent graft function; and all had undetectable viral load at approximately 2 weeks after transplantation which remained undetectable at 6 months.
The investigators were able to begin the DAA treatment regimen within hours of transplantation for all study participants regardless of their insurance coverage because of hospital funding for the study. Blumberg emphasized the importance of this capability for the viability of the procedure.
"It is imperative that transplantation centers determine how antiviral agents will be provided in advance of acceptance of organs from HCV-positive donors," Blumberg indicated.
The trial report, “Heart and Lung Transplants form HCV-Infected Donors to Uninfected Recipients,” and editorial, “Organs from Hepatitis C Virus–Positive Donors,” were published in The New England Journal of Medicine.