Associated Risks

Risks to consider when evaluating HIV-positive to HIV-positive transplantation include HIV superinfection, transfer of resistant virus, and HIV transmission to health care workers.6,12,17 Although studies demonstrate a low rate of OIs in HIV-positive kidney and liver transplants,5,8 the risk of transplanting an HIV-resistant viral strain is a major concern.5 If a recipient contracts a superinfection with a resistant virus, then the recipient often is treated with PIs, which can lead to increased risk for rejection.12

Social risks are a factor as well. The global campaign “U=U” (undetectable = untransmittable) spreads awareness that persons taking ART who have an undetectable viral load have zero risk of sexual transmission of HIV. The same cannot be assumed about potential transmission of HIV via liver transplants.8 In addition, a donor’s race may affect outcomes. Black patients have increased rates of glomerulopathy including HIV-associated nephropathy.3,5

Factors Associated With Rejection

Management of the transplanted organ can be complex due to drug interactions and an increased risk of rejection.8 Compared with HIV-negative recipients, HIV-positive recipients have an approximately 3 times higher risk for acute rejection.13 Muller et al examined cumulative survival rates among 27 patients with an HIV-positive to HIV-positive kidney transplant at 1, 3, and 5 years; results were 84%, 84%, and 74%, respectively. Among the 27 patients, 5 patients had an acute rejection episode.13


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The cause of the higher rejection rates is still unclear. Many factors, including medications, infections, and organ rejection, affect allograft dysfunction. Increased rejection rates occur especially in the presence of HCV coinfection.6 Malat et al propose that “HIV itself causes immune dysregulation and an inflammatory milieu that enhances allorecognition by humoral and cellular mediated pathways,” which increase rejection rates.2

Another hypothesis accounts for host and drug-related factors: elevated host CD3 levels have been definitively linked to rejection (CD3 + HLA-DR+ cells in HIV+ patients).5 According to Sparkes et al, “continued CNI overexposure can contribute to allograft loss through the development of chronic allograft nephropathy.”18 Dosing of CNIs can be complex due to renal dose adjustments that are needed. Signs and symptoms of acute rejection may not always be present. Monitoring is a crucial part of post-transplant management. Persistently elevated serum creatinine and liver enzymes warrant an allograft biopsy.13,17,18

Infections also can result in post-transplant complications. One study observed the differences between infections in podocytes and tubular cells after kidney transplantation. Results showed a faster decline in graft function in podocytes compared with tubular cells. Researchers suggest this relationship is possibly due to poorer glomerular filtration rates in podocytes.13

In a retrospective study, Araiz et al concluded that patients with HCV/HIV coinfection had higher mortality compared with patients with HCV alone (44.1% vs 33%). Results were of clinical significance but were not statistically significant.1

Future Research

There is still much to study in the growing field of HIV-positive organ transplantation. Cell-free DNA assays can be used to diagnose allograft injury in kidney transplant recipients, but there are limited data on HIV-positive recipients.17 Further studies with HIV-positive recipients can aid in earlier detection of injury and earlier intervention. Other areas of future study include access to HIV transplants, optimal immunosuppression and ART regimens, management of donor-derived transmission of a resistant HIV strain, and prevention of acute and chronic rejection.16 Transplant research primarily has been on kidney and liver transplants in HIV-positive adults. Further studies are needed on the outcomes of heart, lung, and pancreas transplants, as well as transplants in pediatric populations.17

Eudiah Ochieng, PA-C, is a graduate of Augusta University. Lisa Daitch, MPA, PA-C, is associate professor at Augusta University.

References

1. Araiz JJ, Serrano MT, García-Gil FA, et al. Intention-to-treat survival analysis of hepatitis C virus/human immunodeficiency virus coinfected liver transplant: is it the waiting list? Liver Transpl. 2016;22(9):1186-1196.

2. Malat GE, Boyle SM, Jindal RM, et al. Kidney transplantation in HIV-positive patients: a single-center, 16-year experience. Am J Kidney Dis. 2019;73(1):112-118.

3. Durand CM, Segev D, Sugarman J. Realizing HOPE: the ethics of organ transplantation from HIV-positive donors. Ann Intern Med. 2016;165(2):138-142.

4. Avettand-Fenoël V, Rouzioux C, Legendre C, Canaud G. HIV infection in the native and allograft kidney: implications for management, diagnosis, and transplantation. Transplantation. 2017;101(9):2003-2008.

5. Werbel WA, Durand CM. Solid organ transplantation in HIV-infected recipients: history, progress, and frontiers. Curr HIV/AIDS Rep. 2019;16(3):191-203.

6. Miro JM, Grossi PA, Durand CM. Challenges in solid organ transplantation in people living with HIV. Intensive Care Med. 2019;45(3):398-400.

7. Health Resources and Services Administration. Organ donation statistics. Accessed November 2, 2020. https://www.organdonor.gov/statistics-stories/statistics.html#:~:text=There%20are%20currently%20over%20109%2C000,and%20Transplantation%20Network%20National%20Data

8. Botha J, Fabian J, Etheredge H, Conradie F, Tiemessen CT. HIV and solid organ transplantation: where are we now. Curr HIV/AIDS Rep. 2019;16(5):404-413.

9. Malinis M, Boucher HW. Screening of donor and candidate prior to solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13548.

10. Botha J, Conradie F, Etheredge H, et al. Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options. AIDS. 2018;32(16):F13-F19.

11. US Department of Health & Human Services. Organ Procurement and Transplantation Network. HOPE Act. Accessed October 28, 2020. https://optn.transplant.hrsa.gov/learn/professional-education/hope-act/

12. Muller E, Barday Z. HIV-positive kidney donor selection for HIV-positive transplant recipients. J Am Soc Nephrol. 2018;29(4):1090-1095.

13. Muller E, Barday Z, Mendelson M, Kahn D. HIV-positive-to-HIV-positive kidney transplantation-results at 3 to 5 years. N Engl J Med. 2015;372(7):613-620.

14. Abara WE, Collier MG, Moorman A, et al. Characteristics of deceased solid organ donors and screening results for hepatitis B, C, and human immunodeficiency viruses. MMWR Morb Mortal Wkly Rep. 2019;68(3):61-66.


15. Wolfe CR, Ison MG. Donor-derived infections: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13547.

16. Ruck JM, Segev DL. Expanding deceased donor kidney transplantation: medical risk, infectious risk, hepatitis C virus, and HIV. Curr Opin Nephrol Hypertens. 2018;27(6):445-453.

17. Blumberg EA, Rogers CC. Solid organ transplantation in the HIV-infected patient: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13499.

18. Sparkes T, Manitpisitkul W, Masters B, et al. Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients. Transpl Infect Dis. 2018;20(6):e12992.