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Abstract
Preliminary data on HIV-positive donor to HIV-positive recipient kidney transplantation suggest promising patient outcomes without adverse events. This is an important step in expanding the donor pool and opportunity for transplantation in HIV-positive patients.
We herein report the first case of HIV-positive donor to HIV-positive recipient kidney transplantation in Denmark. Our patient has demonstrated a successful post-transplant course with excellent 1-year graft function, no rejection episodes, good virological control with undetectable HIV RNA, no signs of HIV-associated nephropathy, and no superinfections or opportunistic infections.
This case corroborates findings from previous studies showing that kidney transplantation from carefully selected HIV-infected donors to carefully selected HIV-infected recipients seems to be a safe and effective treatment option, and supports the opportunity to expand the organ donor pool for this group of patients with end-stage renal disease.
- Infectious diseases
- HIV / AIDS
- Renal medicine
- Renal transplantation
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Background
Advances in antiretroviral therapy have rendered HIV infection a manageable disease, yet the risk of end-stage renal disease (ESRD) remains high among HIV-infected patients.1
Kidney transplantation provides a substantial survival benefit compared with dialysis for HIV-infected patients with ESRD and is now considered the treatment of choice.2 3 However, organ scarcity is an ongoing challenge for many transplant candidates.
To address this challenge in HIV-infected patients, utilisation of HIV-positive donors for HIV-positive recipients (HIV D+/R+) was pioneered in South Africa in 20084 and has since encouraged several transplant centres to use HIV-positive donors with reports of excellent patient and graft survival as well as virological control.4–10
Kidney transplantation of HIV-positive recipients is generally more challenging given the need for an accurate balance of immunosuppressive and antiviral therapy next to possible higher rejection rates. Major concerns regarding use of HIV-positive donors for this population are additional risk of transmission of a different (and possibly resistant) strain of HIV, loss of virological control and risk of other donor-derived infections. Nevertheless, based on the recently published experiences with promising outcome,4–10 it seems reasonable to consider this option for carefully selected HIV-positive patients with ESRD. We herein report the first case of kidney transplantation from an HIV-positive deceased donor to an HIV-positive recipient in Denmark.
Case presentation
The recipient was a male in his 50s diagnosed with HIV-infection and ESRD secondary to polycystic kidney disease 14 years ago. HIV viral load remained undetectable after starting his treatment using combined antiretroviral therapy with darunavir (with ritonavir as pharmacokinetic booster), dolutegravir and lamivudine. CD4 counts were continuously above 200 cells/µL and there had been no history of opportunistic infections.
Seven years later he underwent orchiectomy after being diagnosed with a stage 1 non-seminoma testicular cancer. Additional chemotherapy with cisplatin and etoposide were given based on local lymph node metastases. No evidence of recurrence had been detected on follow-up.
He progressed to ESRD within the same year and haemodialysis was initiated.
After 3 years he was evaluated and found eligible for a kidney transplant after consulting his medical oncology physicians. Additional evaluations regarding his HIV status and potential drug interactions were conducted by specialists in infectious diseases at our hospital prior to waitlisting. Antiviral treatment was changed to dolutegravir, lamivudine and abacavir to prevent potential future drug interactions with immunosuppressive medication.
The patient received an ABO-compatible kidney transplantation from an HIV-positive deceased donor.
The donor was a male in his 20s originally from Southern Africa, who was declared brain dead following traumatic subarachnoid haemorrhage. He was diagnosed with HIV 8 years earlier. The most recent CD4 count was 940 cells/µL and HIV viral load undetectable for the past 6 years. His HIV medication consisted of emtricitabine, tenofovir disoproxil fumerate and darunavir (with cobicistat as pharmacokinetic booster) and with no history of drug resistance. He had never developed an AIDS defining illness or any other infections. Serology was negative for hepatitis B and C, human herpes virus 6–8 and syphilis. cytomegalovirus (CMV) and Epstein-Barr virus serology indicating previous infection. He had a creatinine level of 71 µmol/L and urine analysis revealed no proteinuria. Assesment of the donor’s HIV status and overall compatibility to the recipient was performed by a specialist team of transplant nephrologists and HIV physicians at our hospital. No resistance testing was performed at baseline. The kidney was accepted after obtaining informed consent from the recipient.
HLA mismatch was 4:2 and the recipient had known pre-transplant donor-specific antibodies (anti A11, 2500 MFI), but flow cytometry crossmatch was negative. It was an uneventful surgical procedure with immediate allograft function (figure 1).
The post-transplant clinical course showing levels of plama creatinine, CD4 count and tacrolimus from day 1 to day 341 after transplantation (Illustration: Christiane Lyngberg-Larsen).
Immunosuppression consisted of tacrolimus, mycophenolate mofetil, prednisolone and basiliximab as induction therapy. Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole was given for the following 6 months. CMV prophylaxis was not given based on donor/recipient positivity for past CMV infection, and CMV was monitored routinely according to local practice for intermediate risk of CMV infection post-transplant.
Serum creatinine dropped from 557 µmol/L to 239 µmol/L within the first 2 days after transplantation. On day 3, a kidney graft biopsy was performed showing no signs of rejection (figure 2). On day 7, the patient was discharged with a creatinine level of 153 µmol/L, stabilising at approximately 110 to 130 µmol/L for the following year post-transplant. Tacrolimus levels remained stable with only one outlier due to incorrect sampling (immediately after medication). Virological control was successful with undetectable HIV viral loads and CD4 counts above 400 cells/mm3.
(A) Light microscopy (Periodic acid-Schiff stain, magnification ×1000) of kidney allograft biopsy performed on day 3 after transplantation, showing mild interstitial inflammation (i1) but no tubulitis or glomerular lesions. (B) Light microscopy (Periodic acid-Schiff stain, magnification ×400) biopsy performed 9 months after transplantation, with normal tubular, interstitial and glomerular findings. (C) Electron microscopy (×5000) shows normal glomerular basement membrane appearance without any immune complex deposits or podocyte lesions.
On day 20, the patient was admitted to the hospital due to urinary tract infection. He had consulted his general practitioner a few days prior to admission and started treatment with oral pivmecillinam. On admission he was treated with piperacillin-tazobactam for 5 days and discharged with a stable graft function. No pathologic organism was isolated.
Approximately 2 months after transplantation a CMV viral load of 2310 U/mL was detected without any symptoms. After treatment with valganciclovir for 4 weeks the patient achieved negative viral load tests. An additional 3 months of valganciclovir prophylaxis was initiated according to local practice at that time. CMV was monitored once a week during treatment and prophylaxis and for the following 2 months. No recurrence of infection was detected after completion of therapy.
A second kidney graft biopsy was performed at 9 months post-transplant showing normal renal histology without any findings of rejection or HIV-associated nephropathy (HIVAN) (figure 2).
Outcome and follow-up
The patient was followed by specialist physicians in nephrology and transplant medicine for the first year post-transplant at our transplant centre. During this period his HIV status and treatment were regularly assessed by specialists in HIV and infectious diseases at our hospital. He is alive and well. He had a stable graft function with creatinine levels of approximately 110 to 130 µmol/L at 1 year post-transplant and virological control remained successful with undetectable HIV viral loads and CD4 counts above 400 cells/mm3. The patient was provided with access to regular physiotherapy by his general practitioner and local community and showed gradual improvement in functional status within the first year after transplantation. After 1 year he was referred to the nephrology department and infectious diseases department at his local hospital.
Discussion
Currently the numbers of HIV D+/R+ solid organ transplants in the United States are increasing under the HIV Organ Policy Equity Act, and ongoing studies are exploring the safety and risks within this field.11
We herein report the first case of HIV-positive donor to HIV-positive recipient kidney transplantation in Denmark. This case corroborates findings from previous studies showing that kidney transplantation from carefully selected HIV-infected donors to carefully selected HIV-infected recipients seems to be a safe and effective treatment option.5 6 8 9 11 12
In 2015, Muller and colleagues performed a prospective study of 27 HIV-positive kidney transplant recipients using HIV-positive donors. The 5-year patient survival rate was 74% and the 5-year graft survival 84% among the patients receiving HIV-positive kidneys. Among the patients receiving HIV-negative kidneys the rates were 85% and 75%, respectively. HIV infection remained well controlled in all patients.8
These findings are also supported by a very recent prospective study by Durand et al, who compared outcomes of kidney transplantations with 25 HIV D+/R+ to 50 HIV D-/R+. This study showed overall excellent transplant and HIV outcomes with no differences between the groups, but a trend towards a higher rejection rate in the HIV D+/R+ was noted.11 The risk of rejection in HIV-positive transplant recipients is already known to be higher than HIV-negative controls and the underlying reasons for this are not fully understood.13 14
A possible risk of HIV superinfection in HIV-positive patients is concerning, if an infection with a second distinct strain of HIV in HIV D+/R+ transplants occurs. The study by Selhorst et al included 25 HIV+/+ kidney transplants and initially donor virus was detected in 32% of recipients, yet no cases of HIV superinfection or long-term detection of donor virus was observed.7 Similar results were found in an observational study including 22 HIV D+/R+ transplantations (14 kidney transplant and 8 liver transplant recipients) with no cases of HIV superinfection.10
HIVAN is rarely reported to recur in the transplanted kidney. The spectrum of renal pathology in HIV-positive individuals is diverse, including lesions related to drug effects, comorbidities and co-infections. Typical HIVAN can manifest as podocytopathies such as collapsing focal segmental glomerulosclerosis, immune complex-mediated glomerular disease, or tubulointerstitial injury with tubular microcysts and interstitial inflammation. A recent review from 2021 reports data from two studies on recurrence of HIVAN in HIV-positive transplanted patients. One study from South Africa found 12 of 51 transplanted patients to have some HIVAN-related changes on biopsy but only two patients lost graft function as a result. A multicentre study from the United States including 150 patients found HIVAN in two patients. There were no correlations between HIV viral load and HIVAN, but patients with recurrent HIVAN had significantly decreased graft survival.12
Regarding opportunistic and donor-derived latent infections, Roland et al report nine cases of opportunistic infections in 274 HIV-positive recipients (150 kidney recipients, 124 liver recipients) consisting of oesophageal and bronchial candidiasis, P. jiroveci infections and one cryptosporidiosis. They also found four cases of cutaneous Kaposi’s sarcoma.14 Durand et al found seven cases of opportunistic infections among 75 HIV-positive recipients and no difference in the proportion of opportunistic infections between the recipient group with HIV-positive donors and HIV-negative donors. The detected cases included oesophageal candidiasis, CMV viraemia and one Bartonella infection. There were no cases of Kaposi’s sarcoma or other malignancies in the HIV-positive donor group.11
This case has demonstrated a successful post-transplant course with excellent 1-year graft function, no rejection episodes, good virological control with undetectable HIV RNA, no signs of HIVAN, and no superinfections or opportunistic infections aside from a brief period of CMV viraemia successfully treated with valganciclovir. This corroborates the overall beneficial findings in recent reports on HIV D+/R+ kidney transplantation and supports the opportunity to expand the organ donor pool with the use of organs from HIV-positive donors to HIV-positive patients.
Learning points
This first Danish case of an HIV D+/R+ kidney transplantation has demonstrated a successful post-transplant course with excellent 1-year graft function.
The use of HIV-positive organs for HIV-positive recipients is an established practice in South Africa and the United States, yet only a few cases from other countries have been reported.
Recent data suggest that HIV D+/R+ kidney transplantation may be an acceptably safe and valuable therapy for HIV-positive patients with end-stage renal disease, and use of organs from HIV-positive donors could help to expand the organ donor pool for HIV-positive patients.
Ethics statements
Patient consent for publication
Footnotes
Contributors CLL and LAØ drafted the manuscript. LAØ and ALL provided critical appraisal and feedback. LAØ revised the manuscript. All authors have read and approved the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.