In this study of two large national databases, we estimated that there are likely several hundred potential HIVDD per year in the US. An average of 534 (range: 481–652) potential donors per year were estimated among inpatient deaths of HIV-infected patients captured in NIS. An average of 494 (range: 441–533) potential donors per year with well-controlled HIV and causes of death compatible with organ donation were estimated among HIV-infected patients in care in the HIVRN cohort. Additionally, an average of 20 (range: 11–34) unanticipated HIV-infected donor referrals per year were identified through UNOS, likely representing a pool of potentially eligible HIV-infected donors separate from those captured in NIS or HIVRN.
To our knowledge, this is the first estimation of the number of medically suitable HIVDD in the US. The finding that there is a significant potential pool of HIVDD among HIV-infected patients who die of causes unrelated to HIV is consistent with the findings of several large studies identifying intentional or unintentional injury as a major cause of mortality among many people living with HIV (1
). Based on the estimate of potential HIVDD from this study, several hundred additional HIV-infected patients could receive HIV-infected but otherwise high-quality kidney and liver transplants every year.
HIV-infected patients with ESLD and ESRD are likely to derive benefit from accepting organs from HIVDD. As life expectancy has dramatically improved in many people living with HIV, ESLD and ESRD account for a considerable amount of morbidity and mortality among HIV-infected patients (27
). HIV-infected patients encounter accelerated rates of liver and kidney disease due in part to hepatotoxic and nephrotoxic HAART, high rates of co-infection with HCV, HIV-associated nephropathy, cocaine induced kidney damage, diabetes mellitus and hypertension (29
). As such, mortality among HIV infected patients awaiting transplantation has been shown to be higher than pre-transplant mortality in their uninfected counterparts (13
The number of HIV-infected patients waitlisted for both kidney and liver transplants has grown substantially since 2000. In 2000, there were 3 kidney transplants involving HIV-infected transplant recipients, whereas in 2009, there were 111 such transplants. The growth in liver transplantation has been less dramatic. In 2000, there were 6 liver transplantations involving HIV-infected transplant recipients and in 2009, there were 29. This trend has been shown at transplantation centers across in Europe, as well (31
). Despite successful early reports of HIVDD transplantation and highly favorable attitudes among people living with HIV and their health care providers, potential attenuation of the organ shortage for HIV-infected patients through the use of HIVDD is limited by US law (15
A valid concern associated with the transplantation of organs from HIVDD to HIV-infected recipients is the development of drug resistance acquired through a HIV superinfection and subsequent acceleration of the recipient’s HIV to AIDS. Evidence suggests that patients with well-established HIV-infection on HAART may be at a lower risk of developing a superinfection because they have fewer host cells that are susceptible to becoming infected with new viral strains (32
). Though it is difficult to define the “ideal” potential HIVDD in the absence of a clinical trial, one approach might be to utilize organs from donors who were on HAART and who were virologically suppressed for at least 6 months prior to donation. In this situation, donors will have virally suppressed HIV (< 50 copies/mL) which should reduce the chance of transmission of resistance. Another approach suggested by Muller et al.
would be to use organs from donors who were HAART naïve and whose HIV was not virologically suppressed (> 50 copies/mL) (16
). In this complex situation, it is recommended to suppress the new viral strain with HAART in order to control the recipient’s superinfection. Though the transmission of a drug resistant superinfection has the potential to negatively impact graft and patient survival, this risk should be carefully balanced against the increased risk of mortality HIV-infected patients experience while awaiting transplantation.
Though the natural history of HCV-infection is markedly different from that of HIV, a parallel situation can be drawn to the use of organs from deceased donors infected with HCV for HCV-infected recipients. This practice has substantially shortened time on the waiting list for these recipients without significantly compromising patient or graft survival (33
). The decision of whether or not to utilize these organs falls within the bounds of clinical acumen, not legal judgment. Should the ban on HIVDD be reversed, waiting time for HIV-infected patients who accept HIV-infected organs would almost certainly decrease. Similarly, as the general waiting list would likely get smaller, waiting time for uninfected people would likely decrease as well, an achievement which would have a far reaching public health impact.
This study has several key strengths. NIS is a nationally representative cohort which enabled us to capture cause of death information and relevant diagnostic information from all HIV-infected patients who died as inpatients in the US. Ordinarily, to qualify as a solid organ donor, an individual must have died in a hospital, making NIS the correct “denominator” for potential HIV infected donors. Patients were excluded based on the presence of conditions incompatible with solid organ donation. The HIVRN enabled us to analyze detailed clinical information, laboratory values, and causes of death in a select population with well-controlled HIV within 12 months of death. The UNOS database enabled us to capture terminal kidney and liver function among patients who were thought to be uninfected and thus who would likely not have been captured by HIVRN or NIS.
Estimates derived from datasets not originally designed to answer our research question are, of course, somewhat limited and based on a number of assumptions. As with any large database, the accuracy of coding in NIS is variable. This may have biased our results by not having accurately captured all relevant diagnostic information. Through NIS, we were unable to reliably assess HIV-stage based on CD4 count and presence of AIDS-defining illnesses. Thus, our criteria were very selective for whom we deemed eligible donors and we may have actually underestimated the pool as a result. Though we identified potential donors whose causes of death are ordinarily compatible with solid organ donation, not all trauma or stroke patients, for example, are medically suitable organ donors. This may have resulted in an overestimation of the potential pool of donors.
Though the demographics of the HIVRN mirror the demographics of HIV-infected US population, it is not a nationally representative cohort. Thus, our scaling may have not appropriately captured inpatient deaths among HIV-infected patients in the US, possibly biasing our results upwards. However, our analysis of HIVRN did take into account deaths from geographically diverse centers with diverse patient populations. Similarly, multi-site studies afford greater generalizability than single-site studies. We were limited in our inferences from the HIVRN by lack of information about organ function at the time of death, so we were unable to differentiate between types of donors as we did with the NIS database. As with the NIS database, we were very selective with whom we deemed eligible potential donors, possibly underestimating the pool of potential donors. We likely underestimated the number of potential donors from the HIVRN due to the large proportion of individuals we excluded without CD4 counts and plasma HIV-1 RNA levels recorded within one year of death.
While the medical reasons for excluding HIVDD have changed over time, there may be several other concerns that merit discussion. First, there is the ever-present possibility of clerical error which may result in the introduction of HIV into a previously uninfected recipient. This is an important consideration which will have to be addressed by the transplant community with appropriate administrative safeguards, perhaps drawing from experience with HCV-infected organs. Second, there is the potential for a population-based association of donation with HIV, which may negatively influence rates of donation. Only upon transplanting HIV-infected transplant candidates with HIVDD organs would the transplant community be able to monitor rates of donation and decide the ultimate balance between increased organ availability and potential changes in image or attitude.
Though our data are preliminary and may require further validation, the findings of this study challenge the current US law banning the transplantation of HIV-infected donor organs. As morbidity and mortality from liver and kidney disease continue to increase among HIV-infected people, demand for solid organ transplant among HIV-infected patients will increase, as will the general waiting list (36
). HIVDD represent a significant potential source of organs for many patients with HIV infection. While donor selection and recipient management will require careful clinical judgment, a legal ban on the use of these organs seems unwarranted and likely harmful.