Despite its very optimistic name, the U.S. government's HIV Organ Policy Equity Act, or HOPE Act, might not actually significantly increase the availability of high-quality organs for people living with HIV who are on the national transplant waiting list, according to the Potential HIV Transplant (PHIT) study presented at ICAAC 2014 by Aaron Richterman of the University of Pennsylvania.
The study estimated that there are only four to five potential HIV-infected organ donors dying in Philadelphia each year who might provide, at best, two to three kidneys and three to four livers -- while, as noted by the researchers, there are around 80 to 100 people living with HIV on the waiting list for transplants in the Philadelphia area alone.
Since only about five to 10 people on the waiting list currently receive transplants each year, even four or five donors would represent a significant increase in the organ pool in Philadelphia.
However, the potential donors identified by the study were older with a high prevalence of hypertension, diabetes and hepatitis C antibody. Consequently, according to Richterman, the organs, and particularly the kidneys, from these potential donors would be of a reduced quality.
There is a large disparity today between the number of organ transplants performed in the U.S. and the number of patients who are on the waiting list for organ transplant.
This waiting list now includes people living with HIV, who were ineligible to receive an organ transplant until relatively recently when antiretroviral therapy made HIV a chronic, manageable condition. However, mounting evidence shows that people living with HIV do worse on the waiting list than their HIV-negative counterparts, indicating that there may be a disproportionately greater need for organs among this population.
In South Africa, where there is a shortage of organ donors, people living with HIV still do not qualify for transplants from HIV-negative donors. In response, Elmi Müller, a surgeon at Groote Schuur Hospital in Cape Town, began transplanting kidneys from HIV-positive deceased donors into HIV-positive recipients in 2008. She reported the first four cases in the New England Journal of Medicine, and reported good outcomes in a larger cohort of patients with HIV-associated nephropathy (which is usually fatal in resource-limited settings) a couple of years later.
It was partly due to these findings that the U.S. Congress passed the HOPE Act in November 2013 to legalize research into HIV-positive organ donation in the U.S.
Because little is known about the potential pool of HIV-infected deceased donors in the U.S., Boyarsky and colleagues retrospectively examined dying patients captured by two databases, the Nationwide Inpatient Sample (NIS) and the HIV Research Network, and estimated that there were approximately 500 potential HIV-infected donors dying in the U.S. each year.
The study had several limitations, however. First, its estimates were based on the causes of death that are ordinarily compatible with organ donation, but the specific circumstances of each death in the study cohort itself were not evaluated. Additionally, the NIS database lacked HIV-specific information like recent CD4 count and viral load that would be important when determining the eligibility of a potential donor. Furthermore, the HIV Research Network lacked information on organ function at the time of death, and the cause of death was identified in less than 40% of the deaths reviewed.
Study Details and Results
In order to determine if a significant number of potential donors actually existed based on more specific and detailed patient information, Richterman and colleagues conducted the PHIT study.
It was a retrospective chart review performed on all deaths in care at six large HIV continuity care clinics in Philadelphia from 2009 to 2014. Potential kidney and liver donors were the focus of the analysis due to the greater need for these organs in people living with HIV.
Of specific interest were the patients in care at the time of their death since it is likely that this group would form the core of future potential donors. The definition for being in care was the same as for the Philadelphia department of health: Having two or more CD4 counts and/or viral loads measured at least 90 days apart within 12 months of death.
Potential donors were identified using the standard criteria for organ donation plus HIV-specific criteria (namely, having a viral load below 200 copies/mL and no active opportunistic infections).
Thirty-four percent of the people living with HIV in Philadelphia are followed at one of the six clinics in the study. In addition, about half the deaths in care in the city from 2009 to 2014 were captured by these clinics.
Potential donor findings:
- HIV-positive individuals dying in care: 508.
- The median age was 53.
- The population was predominantly male and African American.
- There was a significant amount of comorbidity including diabetes and hypertension; nearly one-third of these patients had cancer.
- 44% were hepatitis C antibody positive.
- 63% of the patients had a suppressed viral load.
- 56% had a CD4 count over 200.
- 20% had documented HIV resistance mutations.
In addition to AIDS-related mortality, non-AIDS malignancy, cardiovascular disease and liver disease all contributed significantly to the cause of death, which is in keeping with the trends reported since the widespread use of antiretroviral therapy. Additionally, cause-specific mortality in the study was strikingly similar -- with the exception of AIDS-related mortality -- to that documented in industrialized settings in recent data published from the D:A:D study.
But how many potential donors were identified in the PHIT study? Logistical issues dramatically reduced the number of qualifying donors.
Of the deaths reported from January 2009 to June 2014 (n = 578)
70 were excluded, not in care
Deaths in care (n = 508)
260 were excluded due to death outside of the hospital
75 were excluded due to unknown place of death (recorded in the chart)
Deaths in the hospital (n = 173)
63 were excluded because they were not on mechanical ventilation
Deaths on mechanical ventilation (n = 110)
87 were excluded, no documented brain death
Among the documented brain deaths (n = 23):
7 were excluded due to a viral load greater than 200
3 were excluded due to a history of malignancy
Leaving 13 potential donors (n = 13)
A closer look at these remaining 13 potential donors found that they had a median age of 53. There was also a significant amount of diabetes, hypertension and hepatitis C antibody among the potential donors, and several of them had evidence of end-stage organ damage.
Just over half of these potential donors had a positive death secondary to anoxic encephalopathy with the rest dying of cerebrovascular accident (CVA, or stroke) and head trauma.
The Scientific Registry of Transplant Recipients (SRTR) has developed organ specific mathematical models that estimate the potential organ yield from a given set of eligible donors. These models deceased the donor expected yield to four to five potential donors who could provide two to three kidneys and three to four livers.
Next the researchers employed standard transplant models to determine organ graft survival based on a variety of donor and recipient characteristics. Models for both the kidney and liver suggested that there was a reduced kidney and liver quality, driven in part by the older age of the potential donors, by the high prevalence of hypertension, diabetes and hepatitis C, as well as by the predominance of African-American race. There were also questions regarding the implication of the HIV factors identified in this study.
As far as HIV history, causes of concern included a history of opportunistic infections in four individuals, questions of whether current drug therapy would need to be continued in recipients and documented HIV resistance mutations in two individuals.
The researchers mentioned that there were a number of limitations to the study -- including the fact that the charts did not contain information about the cause of death in at least 12% of the deaths, the applicability of models derived from HIV-negative donors to donors with HIV is unknown, and there are a number of logistical constraints that would potentially further limit the number of qualifying organs that would be available in a reasonable time after death.
However, there was also no active HIV organ transplant program in place in the city -- or reason to track potential donors.
It is clear that both the size of the population of potential donors and their health status at time of death will be significantly different in the U.S., and perhaps all industrialized countries, than in South Africa. In South Africa, there are millions of people living with HIV who were not, by this definition, in care or on antiretroviral therapy, and yet the outcomes in South Africa were still better than in the absence of organ transplants.
At the same time, a large proportion of people living with HIV in the U.S. are not on treatment either. Ultimately, the goal of the HOPE Act is to develop research protocols and criteria to establish whether and how organ transplant policies should change. Engagement of the community in the process will be necessary to ensure that safer options are available for people living with HIV in need of an organ transplant.
Theo Smart is an HIV activist and medical writer with more than 20 years of experience. You can follow him on Twitter @theosmart.