Is it acceptable to intentionally expose a transplant recipient to infection?

Issue: June 2018

To expand the organ donor pool, physicians in the United States have begun transplanting kidneys and livers from hepatitis C-infected donors into HCV-negative recipients who are treated with direct-acting antivirals, or DAAs. Infectious Disease News asked Christine M. Durand, MD, assistant professor of medicine and oncology and a transplant infectious diseases specialist at Johns Hopkins University School of Medicine, about the ethics of giving someone an infection they did not already have. Durand helped launch the EXPANDER trial at Johns Hopkins, a small study of 10 HCV-negative patients who received HCV-positive kidneys.

More than 100,000 Americans are waiting for a lifesaving organ transplant — and many will die before receiving an organ offer. Thus, efforts to expand the pool of organ donors are critical. One innovative strategy is maximizing the use of organs from donors with an increased risk for infection or a known infection.

Ideally, new infections would be avoided around the time of transplant. However, remaining on a waitlist also carries a real risk for death. What is an acceptable risk when it comes to infected or potentially infected donors? Deceased donors at risk for HIV, hepatitis B virus or HCV due to behaviors such as injection drug use are considered increased infectious risk donors (IRDs). However, the true increase in risk is not very high. The actual risk for transmission with an IRD transplant is less than 1 in 10,000 for HIV and less than 1 in 1,000 for HCV. With the advent of DAAs, HCV can be reliably cured in more than 95% of patients.

For patients with end-organ disease awaiting transplant, the risk for death on the waitlist needs to be weighed against the risk for acquiring a treatable infection.

Today, amid a national opioid epidemic, more than one in eight organ donors has died of an overdose. A recent study reported a 23-fold increase in transplants using organs from overdose death donors from 2000 to 2016; more than half of overdose death donors were considered IRD, and 18% were infected with HCV. Patients who received transplants from these donors had excellent outcomes; patient survival and organ function were similar (or better) when compared with trauma or medical death donors.

Recently, two pilot clinical trials — the THINKER study at the University of Pennsylvania and the EXPANDER trial at Johns Hopkins — investigated the use of kidneys from HCV-positive deceased donors for transplant in HCV-negative recipients. In other words, study participants were intentionally exposed to or infected with HCV. In the THINKER study, 10 patients were cured postoperatively of HCV with DAAs. In EXPANDER, DAAs were successfully used as prophylaxis to prevent HCV infection in 10 patients.

Even before these innovative trials, transplant teams routinely infected transplant recipients with other infections. Today, more than half of all CMV-negative transplant recipients receive a CMV-positive donor organ. These transplants are routine — and CMV is suppressible, not curable, unlike HCV.

Is it reasonable to intentionally give a transplant recipient an infection? In the words of one EXPANDER study participant, “If I gauged the risk of staying on dialysis against what to me seemed like a very slight risk with this ... it was a no brainer.”

References:
Durand CM, et al. Ann Intern Med. 2018;doi:10.7326/M17-2451.
Durand CM, et al. Ann Intern Med. 2018;doi:10.7326/M17-2871.
Goldberg DS, et al. N Engl J Med. 2017;doi:10.1056/NEJMc1705221.

Disclosure: Durand reports receiving research grants from Merck, GlaxoSmithKline and ViiV Healthcare and serving on advisory boards for Gilead Sciences.