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A Source of Treatment for Those Who Were (Almost) Lost: Human Immunodeficiency Virus–Positive to Human Immunodeficiency Virus–Positive Kidney Transplantation—Results at 3 to 5 Years

Stock, Peter G. MD, PhD1

doi: 10.1097/TP.0000000000000893
In View: Game Changer
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1 University of California, San Francisco Medical Center, San Francisco, CA.

The author declares no conflicts of interest.

Correspondence: Peter G. Stock, MD, PhD, University of California, San Francisco Medical Center, 400 Parnassus Ave., 7th Floor San Francisco, CA 94143. (Peter.Stock@ucsfmedctr.org).

In a true game changer, a New England Journal of Medicine article by Muller and colleagues reported that transplantation of kidneys from human immunodeficiency virus (HIV)–positive deceased donors into HIV-positive recipients was safe and effective.1 Most importantly, the Cape Town team has “changed the game” for HIV-infected patients with renal failure in South Africa. Although a misnomer in this context, transplantation using HIV organs from HIV-infected deceased donors was a lifesaver, rather than a “game changer” for many of the HIV-infected patients with renal failure in South Africa. Because state-funded renal replacement programs in South Africa are limited, the bold strategy to use organs which otherwise would have been discarded was the only opportunity for survival. Dr. Muller's perseverance in pushing this life saving innovative approach forward in the face of initial resistance is commendable and has already had an impact on US laws. In November of 2014, President Obama signed into law the HIV Organ Policy Equity (HOPE) Act, ending the federal ban on the procurement of organs from donors infected with HIV. As a side note, a welcoming change to the usual unidirectional “game” of exporting innovation from the developed to the developing world.

The rationale for using HIV positive organs in HIV-positive recipients in South Africa was clear because most of the HIV-positive patients in renal failure did not have the funding necessary for dialysis. However, in the United States, the potential for receiving HIV-positive organs will also play an important role in expediting the time to either liver or kidney transplant, in turn, significantly impacting patient and graft survival rates. In many parts of the United States, waiting times for deceased donor kidneys are in excess of 7 years, and the negative impact of longer dialysis times have been well characterized.2 Based on the estimated number of viable deceased donors, waiting times for HIV-positive recipients willing to accept an HIV-positive organ would likely be less than 1 year. For liver recipients, the opportunity to get transplanted with a lower Model for End-stage Liver Disease (MELD) score and before progression of liver disease is of benefit to all liver transplant recipients, and of paramount importance to HIV-positive recipients. In the report from the US NIH multicenter trial, outcomes were particularly poor in HIV/Hepatitis C virus (HCV) coinfected recipients who had muscle wasting (BMI<21) and renal failure, both associated with progression of liver disease required to obtain the higher MELD scores necessary for organ allocation.3 Poor outcomes in this group of patients has prompted many centers to abandon liver transplantation in the HIV/HCV coinfected population, just as the newer and highly effective direct acting antiviral agents against HCV are becoming available. Clearly, the opportunity to transplant these patients at a lower MELD will have a positive impact on outcomes in this challenging cohort of patients and complement the dramatic effect of the highly effective direct acting antiviral agents on clearing HCV.

“…transplantation using HIV organs from HIV infected deceased donors was a lifesaver, rather than a ‘game changer’ for many of the HIV infected patients with renal failure in South Africa.”

Although the numbers of deceased donors have stagnated, most increases in the deceased donor pool have been in the extended criteria category. When looking at estimates of Boyarsky et al4 with estimated numbers of approximately 500 potential HIV-positive donors per year, it is important to know that those calculations excluded “extended” donors. Indeed, the outstanding results observed in Muller's series of kidney transplantation from 28 HIV-positive donors into HIV-positive recipients were better than those observed in the US NIH multicenter trial.5 Even if numbers of more ideal HIV deceased donors are significantly lower than the estimates by Boyarsky et al, the opportunity for a new pool of viable donors is apparent. With many advantages when using HIV-positive donors, there remain unknown risks. A potential risk of superinfections with more virulent/resistant strains of HIV is an obvious risk, although this was not a problem in Muller's experience. Because most of the HIV positive donors used in the Cape Town experience were treatment naive, the risk of a mutated and more virulent strain, at least in theory less likely than in the combined antiretroviral therapy experienced HIV-positive US population. Although this potential danger of superinfection will need to be part of an informed consent, the likelihood of transmitting a virulent strain which would escape immunologic control is unlikely. With an increasing number of agents constituting combined antiretroviral therapy, HIV specialists are capable of providing regimens which can control a mutated strain. Indeed, in the US multicenter trial with 150 kidney transplant recipients and 125 liver recipients, progression of HIV related to loss of viral control had not been an issue.3,5

A potentially more concerning risk will be recurrent HIV nephropathy, which was noted in 3 of the patients in the South African trial.1 Recurrent HIV nephropathy was not observed in the US trial as evidenced by an absence of proteinuria. Of note, however, only for cause biopsies were performed in this study. A concerning report from Canaud et al6 reported on the presence of HIV virus in greater than 2 of 3 of renal biopsies in HIV-positive recipients (n=19). Moreover, in 6 of 19 patients (38%), the HIV virus localized in the podocytes. Transplant recipients in the latter group developed proteinuria and ultimate loss of graft function. The differences between the French and US experience remains unclear.7 Regardless, the findings by Canaud could have significant implications as the United States move forward with the implementation of the HOPE Act. The US centers participating in the HOPE Act will be required to participate in an IRB-approved protocol which follows guidelines currently being developed by the National Institutes of Health. It will be important to collect donor tissue and monitor recipients for potential HIV infections in allografts to assure the optimally utilization of HIV-positive donors while identifying which HIV-positive donors should be avoided. Moreover, safety and efficacy of using livers from HIV positive donors remain to be tested, but similar concerns related to an HIV reservoir in the HIV-positive liver need to be studied.

Ultimately the benefits of providing an HIV-positive organ to expedite transplantation for HIV-positive recipient clearly outweigh theoretical risks. Obviously, the only way to get a more accurate assessment of the risk/benefit ratio will be to move forward with using these valuable donor organs for an increasing population of HIV-positive patients in need of transplantation. Thanks to the bold and pioneering work by Dr. Muller and her colleagues, the United States will be able to move forward with this important trial.

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REFERENCES

1. Muller E, Barday Z, Mendelson M, et al. HIV-positive-to-HIV-positive kidney transplantation—results at 3 to 5 years. N Engl J Med. 2015; 372: 613–620.
2. Meier-Kriesche HU, Schold JD. The impact of pretransplant dialysis on outcomes in renal transplantation. Semin Dial. 2005; 18: 499–504.
3. Terrault NA, Roland ME, Schiano T, et al. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transpl. 2012; 18: 716–726.
4. Boyarsky BJ, Hall EC, Singer AL, et al. Estimating the potential pool of HIV-infected deceased organ donors in the United States. Am J Transplant. 2011; 11: 1209–1217.
5. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med. 2010; 363: 2004–2014.
6. Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, et al. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol. 2014; 25: 407–419.
7. Stock PG. Kidney infection with HIV-1 following kidney transplantation. J Am Soc Nephrol. 2014; 25: 212–215.
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