Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies.

BACKGROUND: HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors. METHODS: We aimed to evaluate the effectiveness of transplantation in HIV-positive patients and highlight some of the important issues reported in the literature. We pooled clinical data from different cohorts to show some of the common issues encountered in HIV-positive transplantation. Furthermore, we searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV-positive patients. RESULTS: We included data from 19 cohort studies and reported on outcomes of the current HIV-positive transplant programs. We made recommendations based on personal experience as well as the experience reported in the literature regarding rejection, opportunistic infection, and HIV-associated nephropathy. Opportunistic infections and malignancies are not a major problem for this population group. CONCLUSIONS: HIV-positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. When utilizing HIV-positive donors, the recurrence of HIV-associated nephropathy in the graft kidney is an issue which can be important. Despite some issues with high rejection rates, HIV-positive patients have similar results to HIV-negative patients posttransplantation.

COVID-19 in an HIV-positive kidney transplant recipient.

We report a case of a 50-year-old male with a history of HIV and kidney transplant who presented with SARS-CoV-2. We also present a review of COVID-19 cases in kidney transplant recipients.

Kidney transplantation from an HIV-positive cadaveric donor.

Kidney transplantation is the gold-standard therapy for select HIV-positive patients with ESRD. Since the Italian Ministry of Health defined the guidelines for organ donation from HIV-positive persons in 2018, we report the first case of renal transplantation from an HIV-positive cadaveric donor in two HIV-positive recipients in Italy. The donor was a 50-year-old male, deceased due to post-anoxic encephalopathy, with a history of HIV infection in HAART, undetectable viral load, and HCV-related chronic hepatitis that had been previously treated. The first recipient was a 59-year-old female with a prior history of drug addiction, and she suffered from ESRD secondary to HIV nephropathy. The patient followed preoperative HAART with a good viral response and undetectable HIV viral load. She also had a history of HCV-related chronic hepatitis that had been successfully treated. The right kidney was uneventfully transplanted. The patient developed an asymptomatic reinfection of endogenous BK virus. The second recipient was a 41-year-old male with ESRD secondary to polycystic kidney disease. The patient was HIV-positive in HAART, with a good viro-immunologic response and an undetectable HIV viral load. He suffered from a severe form of hemophilia A and HCV-related chronic hepatitis, which had been previously treated with undetectable HCV RNA. The left kidney was uneventfully transplanted. At the end of follow-up, both patients had a healthy condition with stable renal function, a persistently good viral response and undetectable HIV and HCV viral loads. These encouraging preliminary results seem to confirm the safety and effectiveness of kidney transplantation from select HIV-positive donors.

In sickness and in health: Living HIV positive kidney donation from a wife to her husband, with 7 years' post-transplant follow-up.

Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for kidney transplantation. After the introduction of ART, several studies have demonstrated comparable patient and graft outcomes between HIV-negative and HIV-positive kidney recipients. The US Congress passed the HIV Organ Policy Equity (HOPE) Act in 2013, which permits research in the area of HIV-positive to HIV-positive transplantation. HIV-infected living donation is also permitted under the HOPE Act. However, there is a concern regarding the safety of kidney donation in an HIV-infected person, given the risk of renal disease associated with HIV infection. We report here the case of successful kidney transplantation from HIV-positive living donor to HIV-positive recipient performed in our center on July 2012. To the best of our knowledge, this is the earliest case done in this medical context to be reported in the literature, therefore, potentially carrying several important messages to the transplantation community. In the present case, the living-donor kidney transplant was performed between a married couple infected with same strain of HIV-1, both on effective ART with efficiently suppressed viral replication and satisfactory pre-transplantation immune status.

HIVAN associated tubular pathology with reference to ER stress, mitochondrial changes, and autophagy.

Human immunodeficiency virus associated nephropathy (HIVAN) is a unique form of a renal parenchymal disorder. This disease and its characteristics can be accredited to incorporation of DNA and mRNA of human immunodeficiency virus type 1 into the renal parenchymal cells. A proper understanding of the intricacies of HIVAN and the underlying mechanisms associated with renal function and disorders is vital for the potential development of a reliable treatment for HIVAN. Specifically, the renal tubule segment of the kidney is characterized by its transport capabilities and its ability to reabsorb water and salts into the blood. However, the segment is also known for certain disorders, such as renal tubular epithelial cell infection and microcyst formation, which are also closely linked to HIVAN. Furthermore, certain organelles, like the endoplasmic reticulum (ER), mitochondria, and lysosome, are vital for certain underlying mechanisms in kidney cells. A paradigm of the importance of said organelles can be seen in documented cases of HIVAN where the renal disorder results increased ER stress due to HIV viral propagation. This balance can be restored through the synthesis of secretory proteins, but, in return, the secretion requires more energy; therefore, there is a noticeable increase in mitochondrial stress. The increased ER changes and mitochondrial stress will greatly upregulate the process of autophagy, which involves the cell's lysosomes. In conjunction, we found that ER stress and mitochondrial changes are associated in the Tg26 animal model of HIVAN. The aim of our review is to consolidate current knowledge of important mechanisms in HIVAN, specifically related to the renal tubules' association with ER stress, mitochondrial changes and autophagy. Although the specific regulatory mechanism detailing the cross-talk between the various organelles is unknown in HIVAN, the continued research in this field may potentially shed light on a possible improved treatment for HIVAN.

Renal transplantation in HIV-positive patients - No more a scare!

Human immunodeficiency virus (HIV) infection has posed as a major global health epidemic for almost three decades. With the advent of highly active antiretroviral therapy in 1996 and the application of prophylaxis and management of opportunistic infections, acquired immunodeficiency syndrome mortality has decreased markedly. The most aggressive HIV-related renal disease is end-stage renal disease due to HIV-associated nephropathy. Presence of HIV infection used to be viewed as a contraindication to renal transplantation for multiple reasons; concerns for exacerbation of an already immunocompromised state by administration of additional immunosuppressants; the use of a limited supply of donor organs with unknown long-term outcomes. Multiple studies have reported promising outcomes at three to five years after kidney transplantations in patients treated with highly active antiretroviral therapy, and HIV is no longer a contraindication for renal transplant. Hence, we present eight HIV-positive patients who received live-related renal transplantation at our center and their follow-up.

HIV Infection in the Native and Allograft Kidney: Implications for Management, Diagnosis, and Transplantation.

The native kidney is a reservoir for human immunodeficiency virus (HIV)-1 and a site of viral replication, similar to lymphoid tissue, gut-associated lymphoid tissue or semen. The ability of the virus to persist may result from either a true latency or sequestration in an anatomic site that is not effectively exposed to antiretroviral therapy. The presence of HIV in kidney epithelial cells will lead progressively to end-stage renal disease. For decades, HIV-infected patients were excluded from consideration for kidney transplantation. Hemodialysis and peritoneal dialysis were the only forms of treatment available to these patients. The introduction of combined antiretroviral therapy has changed the overall prognosis of these patients and allowed them to benefit from kidney transplantation without an increased risk of opportunistic infections or cancer. However, we recently established that HIV-1 can infect kidney transplant epithelial cells in the absence of detectable viremia. The presence of HIV in kidney cells can manifest itself in multiple ways, ranging from indolent nephropathy and inflammation to proteinuria with glomerular abnormalities. Because the tools that are available to diagnose the presence of HIV in kidney cells are complex, the rate of infection is certainly underestimated. This finding will certainly have implications in the management of patients, particularly for HIV-positive donors. The purpose of this review is to highlight recent evidence that the allograft kidney can be infected by the virus after transplantation as well as the associated consequences.

Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy.

INTRODUCTION: Several studies have demonstrated that renal transplantation in HIV positive patients is both safe and effective. However, none of these studies have specifically examined outcomes in patients with HIV-associated nephropathy (HIVAN). METHODS: Medical records of all HIV-infected patients who underwent kidney transplantation at Johns Hopkins Hospital between September 2006 and January 2014 were reviewed. Data was collected to examine baseline characteristics and outcomes of transplant recipients with HIVAN defined pathologically as collapsing focal segmental glomerulosclerosis (FSGS) with tubulo-interstitial disease. RESULTS AND DISCUSSION: During the study period, a total of 16 patients with HIV infection underwent renal transplantation. Of those, 11 patients were identified to have biopsy-proven HIVAN as the primary cause of their end stage renal disease (ESRD) and were included in this study. They were predominantly African American males with a mean age of 47.6 years. Seven (64%) patients developed delayed graft function (DGF), and 6 (54%) patients required post-operative dialysis within one week of transplant. Graft survival rates at 1 and 3 years were 100% and 81%, respectively. Acute rejection rates at 1 and 3 years were 18% and 27%, respectively. During a mean follow up of 3.4 years, one patient died. CONCLUSIONS: Acute rejection rates in HIVAN patients in this study are higher than reported in the general ESRD population, which is similar to findings from prior studies of patients with HIV infection and ESRD of various causes. The high rejection rates appear to have no impact on short or intermediate term graft survival.

Current status of kidney transplantation in HIV-infected patients.

PURPOSE OF REVIEW: To summarize the most current literature on transplant outcomes in HIV-infected kidney recipients. RECENT FINDINGS: HIV-infected recipients overall have excellent patient and allograft outcomes. Acute rejection, delayed graft function, drug-drug interactions and limited access to organs have emerged as important issues for HIV-infected kidney transplant patients. The subset of patients who are coinfected with hepatitis C virus do not fare as well and improving their outcomes should be a focus of future research in the field. SUMMARY: Renal transplantation remains the optimal treatment for end stage renal disease in the HIV-infected patient.

Successful outcome of renal transplantation in a child with HIV-associated nephropathy.

Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active antiretroviral therapy in late stages of HIV disease with high viral load and low CD4 cell count. Renal transplantation has been successful in a large series of carefully selected HIV-infected adults, with patient and renal allograft survival approaching those of non-HIV-infected patients. We report the successful outcome of living related renal transplantation in a vertically transmitted HIV-infected 8-year-old girl with end-stage kidney disease on haemodialysis due to HIVAN. The pretransplant preparations and post-transplant care, with particular emphasis on immunosuppression and avoidance of opportunistic infections, are discussed.

Pretransplantation pharmacokinetic curves of tacrolimus in HIV-infected patients on ritonavir-containing cART: a pilot study.

BACKGROUND: Ritonavir is an extremely strong inhibitor of P450 cytochrome 3A, which is the main metabolizing enzyme of tacrolimus. Subsequently, the pharmacokinetics of tacrolimus are affected to a large extend by the coadministration of ritonavir in HIV-infected transplant recipients. Therefore, to prevent overexposure directly posttransplantation in HIV-infected patients on ritonavir-containing cART, the predictive value of a pretransplantation pharmacokinetic curve of tacrolimus was explored. METHODS: A pretransplantation pharmacokinetic model of tacrolimus in these patients was developed, and a posttransplantation dosing advice was established for each individual patient. The pharmacokinetic population parameters were compared with HIV-negative patients, and predictive value of the pretransplantation curves was assessed in patients after the transplantation procedure. RESULTS: No significant difference was found between the model-predicted and actual posttransplantation 24 h-tacrolimus levels (14.6 vs. 17.8 ng/mL, P=0.19). As the simulated pharmacokinetic curves lacked an absorption peak every 12 h, the mean 12 h-AUC was approximately 40 % lower compared with AUC's reported in HIV-negative recipients, when similar trough levels were targeted. CONCLUSION: In conclusion, pretransplantation curves of tacrolimus seem a promising tool to prevent overexposure directly posttransplantation in patients on ritonavir-containing cART and raising trough levels to achieve an exposure equivalent to HIV-negative recipients is suggested.

[Kidney transplant in patients with HIV infection]. / IL trapianto di rene nel paziente con infezione da HIV.

Until recently, human immunodeficiency virus (HIV) infection was an absolute contraindication to solid organ transplantation because it was feared that the anti-rejection therapy could result in accelerated HIV disease. At the end of the 1990s it became clear that HIV infection, once deemed a fatal disease, could be effectively turned into a chronic condition by the use of highly active antiretroviral therapy. Since then, the mortality rate from opportunistic infections has decreased dramatically, while liver and renal insufficiency have become the major causes of morbidity and mortality in these patients in the long term. A growing number of HIV patients develop end-stage renal disease secondary to immune-mediated glomerulonephritis, HIV-associated nephropathy, nephrotoxic effects induced by antiretroviral medication, or diabetic and vascular nephropathy, and therefore need maintenance dialysis. For this reason we have to reconsider kidney transplant as a possible treatment option. During the last decade, the results of many studies have shown that transplantation can be safe and effective as long as the HIV infection is effectively controlled by antiretroviral therapy. The short- and medium-term patient and graft survival rates in HIV-positive transplant recipients are comparable with those of the overall transplant population, but the incidence of acute rejection episodes is higher. The main clinical problem in the management of HIV-positive transplant recipients originates from the interference between immunosuppressive regimens and antiretroviral drugs. Thus, a close collaboration between infectious disease specialists and nephrologists is mandatory in order to optimize transplantation programs in these patients.

Alloantigen-specific response is preserved and autoimmunity is maintained in an HIV-positive patient with immunoglobulin A nephropathy undergoing renal transplantation: a warning about long-term reduction in immunosuppression--a case report.

We report the case of a 43-year-old patient with HIV infection treated with antiretroviral therapy, which was complicated by immunoglobulin A (IgA) nephropathy and renal failure, who subsequently was transplanted using a deceased donor kidney transplant. During the late posttransplant period we detected specific anti-donor HLA antibodies showing a preserved alloantigen response. A renal biopsy showed no acute cellular or humoral rejection, an absence of pericapillary C4d deposits or SV40 infected cells, but demonstrated IgA mesangial deposits and mild interstitial fibrosis probably related to calcineurin inhibitor toxicity. This case shows that allo- and autoimmune responses are preserved despite immunosuppressive treatment and original HIV disease. It warns of the importance of maintaining optimal monitoring and immunosuppressive strategies among HIV-positive recipients who become solid organ transplant recipients.

Kidney transplantation at UCSF: 8,300 transplants and onward.

Overall, the kidney transplant experience at UCSF has been highly successful. The program has made significant contributions to the field of kidney transplantation with advancements in organ allocation, crossmatching, clinical trials, pediatric transplantation, organ preservation and transplantation in HIV-positive recipients, to name a few. The program was built on the shoulders of giants in kidney transplantation but continues to be innovative and bold and does not rely on past success to pave the future. The program is truly a tribute to the many surgeons, nephrologists, fellows and ancillary personnel who have made this program a premiere center for kidney transplantation over the past 40 years.

Management of HIV-infected patients with ESRD.

Patients infected with human immunodeficiency virus (HIV) often progress to ESRD. In the era of highly active antiretroviral therapy, the care of these patients has become increasingly complex as survival has improved. Patients infected with HIV who also have ESRD are at risk for critical interactions between medication regimens to treat both of these conditions. Within this population, hemo- and peritoneal dialysis as well as kidney transplantation are life sustaining but present a host of obstacles related to HIV monitoring and risk of transmission, access thrombosis, infection, and rejection. Knowledge of antiretroviral regimens, drug interactions, and HIV resistance as well as the management of ESRD in the presence of HIV infection will improve the care of these unique patients.

Long-term survival after kidney transplantation in an HIV-positive patient.

Only a decade ago, human immunodeficiency virus (HIV)-seropositivity was considered an absolute contraindication for organ transplantation. With the currently available experience, it is no longer justified to deny HIV-positive patients access to transplantation. To the best of our knowledge, we here present the longest surviving HIV-positive patient after renal transplantation. The follow-up period after renal transplantation in this HIV-positive female is now 13 yr and she is in good general condition with excellent renal function. Throughout her post-transplant follow-up, we encountered a number of problems that are illustrative of the HIV-positive patient.

ABO incompatible renal transplantation in an HIV-seropositive patient.

To date, there have been no reports of successful ABO blood group incompatible renal transplantation in HIV patients. We describe a case of a 47-year-old African American man with end-stage renal disease secondary to HIV-induced nephropathy who underwent a live unrelated (spouse) donor ABO blood group incompatible transplant using an intravenous immunoglobulin/plasmapheresis preconditioning regimen with interleukin-2 receptor antagonist induction along with tacrolimus and mycophenolate mofetil maintenance. The postoperative course was complicated by two acute cellular rejection (Banff Ia) episodes that were successfully managed with corticosteroid boluses and the addition of corticosteroids to maintenance immunosuppression. Antibody-mediated rejection was not observed on biopsy. The patient reached a serum creatinine nadir of 2.0 mg/dL on postoperative day 20, which has now been maintained for 170 days. His current CD4 count was 410 cells/microL.