1253There are currently nearly 120,000 Americans awaiting solid organ transplantation on the United Network for Organ Sharing (UNOS) waiting lists. Unfortunately, only a small fraction will get the opportunity for transplantation this year. While deceased organ donation has continued to increase (with 9,079 donors in 2015), this increase is relatively small and pales in comparison to the rate at which we are adding people to these waiting lists (currently >30,000 annually). The end result—and the harsh reality—is that many of these people waiting will never be transplanted unless they can identify a living donor (for a kidney or liver transplant) or we find a way to dramatically increase the donor pool. It is not for lack of effort that there are not enough deceased donors, but societal attitudes and personal beliefs about organ donation have not changed significantly and, as a result, the number of deceased donors has increased less than 15% over the last decade .
The vast majority of the patients (>80%) awaiting transplantation are those with end-stage renal disease who need a kidney transplant. The impact of this has individual and societal implications. Dialysis, which for most consists of being hooked up to a machine in a dialysis center for 4 hours three times a week, is debilitating, draining, and most are unable to work or enjoy a good quality of life. Dialysis can only replace about 10% of the lost kidney function. Additionally, the risk of death from heart attacks and strokes is significantly higher for those on dialysis. The cost of this care, burdened by us all via the End-Stage Renal Disease (ESRD) Network of Medicare, is staggering and increasing steadily. Transplantation has been modeled and shown to have a cost saving over dialysis in addition to the more obvious quality-of-life improvements and decreased overall mortality rate.
Can HIV+ patients really have a transplant?
Because of the success of kidney transplantation, the indications for transplantation have continued to expand including younger and older extremes as well as for those with significant comorbidities, including infection with Human Immunodeficiency Virus (HIV). A recently concluded National Institute of Health (NIH)-sponsored, 5-year, multicenter study evaluated kidney and liver transplantation in patients with HIV using HIV-negative (HIV-) donors. With the advent of anti-retroviral therapies over the last two decades, those infected with HIV enjoy longer lives and are now confronted with the same realities of medical complications from diabetes and hypertension as those uninfected.
While once considered an absolute contraindication to transplantation because of the need for immunosuppression to prevent rejection, anecdotal and now formal experiences have proven that these patients, when carefully selected with controlled HIV, can be successfully transplanted. In fact, HIV is more about immune dysregulation than immune deficiency and, somewhat counter-intuitively, many antirejection immunosuppressive medications actually work synergistically with the HIV anti-retroviral medications. For HIV-positive (HIV+) patients with maintained CD4 counts, undetectable HIV viral loads and no history of significant opportunistic infections, transplantation can be lifesaving and is justifiable.¹
The HOPE Act
In the 1980s, HIV and the associated acquired immunodeficiency syndrome (AIDS) were feared as a pandemic. And when the National Organ Transplant Act (NOTA) was passed by Congress in 1984, the recovery of organs from HIV+ donors was banned. With the improved therapies, HIV is now associated with much less stigma and HIV has become a chronic disease that can be successfully managed in most cases. Given the success of transplantation for those with HIV utilizing HIV- donor organs, the transplant community raised the question about the ban on procuring HIV+ donor organs for use in HIV+ recipients. In South Africa, where until very recently the government would not allow dialysis to be given to anyone infected with HIV, transplant surgeon Elmi Muller was tired of seeing those with kidney failure and HIV die and successfully performed the first transplants using HIV+ organs.²
This previously untapped pool of donors could potentially increase the global pool of organs for everyone. Those with HIV could directly benefit by receiving these organs and those without would benefit by having the waiting lists reduced and, thereby, their own waiting times for a non-infected organ. In addition, because of the cost-effectiveness of transplantation, this would have significant Medicare savings. While UNOS did not previously maintain data on potential HIV+ donors because of the NOTA ban, studies were done that conservatively estimated there could be as few as 500 and as many as 2,500 HIV+ donors in the United States annually. This would easily be the largest increase in the donor pool ever. The stage was set and the HIV Organ Policy Equity (HOPE) Act garnered bipartisan support and was one of only 57 laws passed in 2013 by President Obama.³ This law makes it legal to procure organs from HIV+ donors for transplantation.
The HOPE Act also mandates that the Secretary of Health and Human Services develop criteria for the conduct of clinical research involving these organs which have now been realized and the first HIV+ organs were successfully procured and transplanted in the United States at John Hopkins Hospital and, subsequently, at Mount Sinai Hospital just a few months ago. There are currently four additional hospitals (including Yale, Alabama, Hahnemann, and the University of California at San Francisco) with approval to proceed. All participating hospitals are required to conduct transplants with HIV+ organs under Institutional Review Board (IRB)-approved research protocols that conform to the Final HIV HOPE Act Safeguards and Research Criteria for Transplantation of Organs Infected with HIV, which were developed by the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH.
Implications of the HOPE ACT
The wait for a kidney transplant in the United States varies significantly based upon one’s blood type and where one lives. In New York, the average wait for someone with blood type O is around 7 years. This wait has only increased and is expected to continue to do so. Quite intimidating, considering the statistics for risk of death while waiting on dialysis; roughly 50% chance of dying within 4 years without transplantation. The HIV+ patients that agree to accept an HIV+ organ will remain on the national waiting lists for any kidney, but will be the only ones considered when an appropriate HIV+ donor is identified. Organ Procurement Organizations (OPOs) are actively being trained and preparing to pursue these donors and a handful has already been procured and transplanted. For those awaiting a kidney, the wait will be dramatically reduced and likely be measured by a few months, not several years. For those awaiting a liver, because there is no such thing as chronic liver dialysis, this can mean the difference between living longer or dying.
While there is much to learn about utilizing these types of organs for transplantation, the potential benefits seem obvious. Theoretically, there are concerns that the HIV viral strains differ and have varying drug resistance profiles, but it remains to be determined if this will have real clinical implications to potential recipients. As we start to use these organs, we as a transplant community are being very careful to select more ideal, younger donors with good graft function and preferably with undetectable HIV viral loads and/or known drug sensitivities. Like any new expansion of criteria, there are sure to be learning curves and challenges. But with the passage of the HOPE Act and its implementation being a success of expanding our horizons to help more people realize transplantation, these efforts should be championed.