HIV-positive Kidney Transplant Recipients Research Articles

Prevalence of osteoporosis and factors associated with bone density in HIV-positive kidney transplant candidates and recipients from an HIV-positive donor

Background: Studies show a high prevalence of osteoporosis and fracture risk in kidney transplant candidates and recipients. However, little is known about the prevalence of osteoporosis among transplant recipients and candidates living with HIV. Objective: To determine the prevalence of osteopenia and osteoporosis and investigate the socio-demographic and nutritional factors associated with BMD in HIV-positive transplant candidates and recipients from an HIV-positive donor. Methods: In this cross-sectional study, 20 HIV- positive transplant recipients and 36 transplant candidates on haemodialysis (HD) and awaiting transplantation had BMD and body composition measured by dual-energy X-ray absorptiometry (DEXA). Vitamin D status was measured using serum 25-hydroxyvitamin D [25(OH)D]. Dietary Vitamin D and calcium intake was obtained from a single 24-hour recall. Results: Participants were mainly black African (92.9%), male (55.4%) with a mean age of 43.8 ± 8.3 years. Serum 25(OH)D levels were low for the group as a whole, with a mean of 22.04 ± 12.74 ng/ml. Osteoporosis was more prevalent amongst transplant recipients (20.0%) than transplant candidates (13.9%). Conversely, osteopenia was present amongst transplant candidates (27.8%). T-scores strongly correlated positively, with lean mass and BMD of the spine (r = 0.707, p = 0.007), and moderately, with each side of the total hip BMD (r = 0.455, p = 0.007 and r = 0.420, p = 0.007). There was a significant positive association between dietary calcium and all BMD sites in transplant recipients only. Conclusion: The prevalence of osteoporosis was similar, and in some cases, lower than in transplant recipients elsewhere. Lean mass was positively associated with BMD, and in transplant recipients, dietary calcium intake was positively associated with BMD emphasising the role of diet and exercise in preserving BMD.

Immunosuppression in HIV-positive kidney transplant recipients.

The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients. Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided. Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients

IntroductionThe management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited.MethodsThis retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression.ResultsThere were a total of 46 switches in 31 of 53 patients (58%). Protocol switches (n = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half (n = 21, 46%) occurred during the transplant admission period, and approximately two-thirds (n = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03–7.48), P = 0.044).ConclusionDespite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen.

Gastrointestinal symptoms in HIV-positive kidney transplant candidates and recipients from an HIV-positive donor

Gastrointestinal symptoms (GIS) are common in kidney transplant candidates and recipients and may be worsened by HIV. Objective: To determine the frequency and severity of GIS in HIV-positive kidney transplant recipients from HIV-positive donors, and those waiting to receive one. A GIS rating scale (GSRS) was completed by 76 participants at baseline and at 6 months. GIS frequency was defined as having at least one symptom (GSRS > 1). Severity was indicated by the GSRS score. Transplant candidates: GIS frequency was 88.9% and 86.3% at baseline and 6 months respectively. Indigestion was the most frequent (79.6% and 66.7% at baseline and 6 months), and severe GIS (GSRS 2.3). Women reported global mean (p = 0.030) severity significantly more than men. Transplant recipients: GIS frequency was 95.2% and 76.2% at baseline and 6 months respectively. At both assessment points, indigestion occurred most frequently (85.7% and 61.9% respectively). Highest GSRS was reported for indigestion at baseline (2.33) and at 6 months (1.33). Waist circumference (WC) was positively associated with the severity of constipation GSRS. GIS are common in both groups, especially indigestions. WC in transplant recipients should be monitored.

Belatacept-based immunosuppressive regimen in HIV-positive kidney transplant recipients.

BackgroundKidney allograft survival in human immunodeficiency virus (HIV)-positive patients is lower than that in the general population. Belatacept increases long-term patient and allograft survival rates when compared with calcineurin inhibitors (CNIs). Its use in HIV-positive recipients remains poorly documented. MethodsWe retrospectively report a French cohort of HIV-positive kidney allograft recipients who were switched from CNI to belatacept, between June 2012 and December 2018. Patient and allograft survival rates, HIV immunovirological and clinical outcomes, acute rejection, opportunistic infections (OIs) and HLA donor-specific antibodies (DSAs) were analysed at 3 and 12 months, and at the end of follow-up (last clinical visit attended after transplantation). Results were compared with HIV-positive recipients group treated with CNI.ResultsTwelve patients were switched to belatacept 10 (2–25) months after transplantation. One year after belatacept therapy, patient and allograft survival rates scored 92% for both, two (17%) HIV virological rebounds occurred due to antiretroviral therapy non-compliance, and CD4+ and CD8+ T-cell counts remained stable over time. Serious adverse events included two (17%) acute steroid-resistant T-cell-mediated rejections and three (25%) OIs. Kidney allograft function significantly increased over the 12 post-switch months (P = 0.009), and DSAs remained stable at 12 months after treatment. The control group showed similar results in terms of patient and kidney allograft survival rates, DSA characteristics and proteinuriaConclusionsSwitch from CNI to belatacept can be considered safe and may increase long-term kidney allograft survival in HIV-positive kidney allograft recipients. These results need to be confirmed in a larger cohort.

Experience with a six-month regimen of Pneumocystis pneumonia prophylaxis in 122 HIV-positive kidney transplant recipients.

Anti-Pneumocystis pneumonia (PCP) prophylaxis is recommended for 3 to 6months post-transplant in HIV-negative kidney transplant recipients. For HIV-positive kidney transplant recipients, there is no definite duration of primary prophylaxis and is often prescribed life-long. The objective of this study was to determine the incidence of PCP in HIV-positive recipients who received 6months of prophylaxis with trimethoprim-sulfamethoxazole or an alternative agent. One hundred and twenty-two HIV-positive recipients received a kidney transplant from 2001 to 2017 at Hahnemann University Hospital. Most patients received induction immunosuppression with an IL-2 receptor antagonist, with or without intravenous immunoglobulin. Only one patient received anti-thymocyte globulin. Maintenance immunosuppression included a calcineurin-inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or sirolimus), and prednisone. Mean CD4 cell count was 461±127cells/uL prior to transplant and 463±229cells/μL at 6 to 12months after transplant. None of the recipients developed PCP after a median follow-up of 2.88years (IQR 1.16-4.87). Based on our observation, a 6-month regimen of PCP prophylaxis may be sufficient among HIV-positive recipients, similar to those without HIV infection.

Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients

BackgroundHuman immunodeficiency virus (HIV)-positive kidney transplant (KT) recipients have been shown to experience higher rejection rates due in part to drug-drug interactions between antiretroviral therapy (ART) and immunosuppression regimens. High tacrolimus (FK) intrapatient variability (IPV) is associated with inferior outcomes in KT. The purpose of this study was to determine the impact of protease inhibitor (PI)-based ART on FK IPV and graft outcomes. MethodsWe performed a single-center review of HIV-positive KT recipients from 2007 to 2017. Percentage coefficient of variation (%CV = (σ/μ) × 100; σ, median; μ, standard deviation) was calculated for FK IPV. FK IPV at 6 and 12 months, graft function, and immune outcomes in PI-based vs non-PI-based KT recipients were compared. ResultsA total of 23 HIV-positive KT patients were identified, of whom 10 were maintained on PI-based ART. Median IPV for the entire cohort at 6 and 12 months was 35.8% and 41%, respectively. Patients on PI-based regimens were proportionally more likely to experience high IPV at both time points. Median FK IPV was numerically higher at 6 months (37.3% vs 26.8%, P = .11) and significantly higher at 12 months (57.8% vs 30.9%, P = .01) for patients on PI-based regimens. Lastly, inferior graft function was observed in PI-based patients. ConclusionOur data suggest that PI-based ART is associated with a higher degree of FK IPV, which may contribute to worsening graft function. Larger studies are warranted to determine the impact of PI-based ART on FK IPV and graft outcomes in this population.

Strongyloides hyperinfection in an HIV-positive kidney transplant recipient: a case report

BackgroundStrongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening.Case presentationA 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1–0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days.ConclusionsThis case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.

Conversion to belatacept maintenance immunosuppression in HIV-positive kidney transplant recipients.

There are only scattered case reports documenting belatacept use in HIV+kidney transplant recipients. We performed a retrospective review to describe short-term outcomes following conversion to belatacept in a cohort of HIV+patients. Patients were included if they were converted to belatacept between May 2015 and May 2019, had an HIV- donor, and received ≥4 doses of belatacept. All patients were treated with non-depleting induction and triple maintenance immunosuppression. Allograft and HIV-related outcomes were collected from the date of belatacept infusion until May 2020. Ten HIV+kidney transplant recipients were identified, who were converted to belatacept a median of 364days post-transplant. At last follow-up (median 3.3years), 8 patients remained on belatacept therapy, and all patients were alive with functioning allografts. Mean estimated glomerular filtration rates (eGFR) improved from 31.6mL/min at baseline to 42.8mL/min at 1year (P=.03). Two patients developed acute rejection, with one necessitating conversion back to tacrolimus. All patients maintained undetectable HIV-1 viral loads at last follow-up. One patient each developed pneumocystis pneumonia and Kaposi sarcoma following conversion, which were responsive to standard medical therapy. In our cohort of stable HIV+kidney transplant recipients, conversion to belatacept was associated with excellent early patient and allograft survival and improved eGFR at 1year.

Outcomes of donor-derived superinfection screening in HIV-positive to HIV-positive kidney and liver transplantation: a multicentre, prospective, observational study

One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection. In this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per μL for liver and >200 cells per μL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262. 14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART. These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients. US National Institute of Allergy and Infectious Diseases and National Cancer Institute.

Barriers to kidney transplant evaluation in HIV-positive patients with advanced kidney disease: A single-center study.

HIV-positive kidney transplant (KT) recipients have similar outcomes to HIV-negative recipients. However, HIV-positive patients with advanced kidney disease might face additional barriers to initiating the KT evaluation process. We sought to characterize comorbidities, viral control and management, viral resistance, and KT evaluation appointment rates in a cohort of KT evaluation-eligible HIV-positive patients. We included patients seen between January 1, 2008, and December 31, 2015, at a primary care HIV clinic who met KT evaluation eligibility by an estimated glomerular filtration rate ≤20mL/min/1.73meters2 or dialysis dependence. The primary outcome was a documented appointment for KT evaluation. Of 3735 patients evaluated at the HIV primary clinic during the study period, 42 (1.6%) were KT evaluation-eligible patients. The median age was 47years, 77% were male, and 95%, black. Median CD4 count was 328cells/mm3 (IQR 175-461). Among the 63% percent with antiretroviral therapy (ART) prescription, 40% had viral loads >200 copies. Among patients with HIV resistance profiles (50%, n=21), 52% had resistance to at least one class of ART. A majority (60%, n=25) were scheduled for KT evaluation appointment, but of those, only 8% (n=2) had evidence of appointments before dialysis dependence. Those without appointments had more schizophrenia (29% vs 4%, P=.02), resistance (78% vs 33%, P=.04), ART prescription (76% vs 48%, P=.04), and more kidney disease of unknown etiology (53% vs 8%, P=.02). Kidney transplant evaluation-eligible HIV-positive patients had a high rate of evaluation appointments, but a low rate of preemptive evaluation appointments. Schizophrenia and viral resistance disproportionally affected patients without evaluation appointments. These data precede the recommendation for universal ART for all HIV+ patients, regardless of CD4 count and viral load, and must be interpreted in the context of this limitation.

Impact of Protease Inhibitor-Based Anti-Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients.

Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p=0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p=0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p=0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p=0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.

Association of tenofovir disoproxil fumarate with primary allograft survival in HIV-positive kidney transplant recipients.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral agent frequently used to treat human immunodeficiency virus (HIV). There are concerns regarding its potential to cause acute kidney injury, chronic kidney disease, and proximal tubulopathy. Although TDF can effectively suppress HIV after kidney transplantation, it is unknown whether use of TDF-based antiretroviral therapy (ART) after kidney transplantation adversely affects allograft survival. We examined 104 HIV+ kidney transplant (KT) recipients at our center between 2001 and 2014. We generated a propensity score for TDF treatment using recipient and donor characteristics. We then fit Cox proportional hazards models to investigate the association between TDF treatment and 3-year, death-censored primary allograft failure, adjusting for the propensity score and delayed graft function (DGF). Of the 104 HIV+ KT candidates who underwent transplantation during the study period, 23 (22%) were maintained on TDF-based ART at the time of transplantation, and 81 (78%) were on non-TDF-based ART. Median age of the cohort was 48years; 87% were male; 88% were black; and median CD4 count at transplantation was 450 cells/mm3 . Median kidney donor risk index was 1.2. At 3years post transplantation, primary allograft failure occurred in 26% of patients on TDF-based ART and in 28% of patients on non-TDF-based ART (P=.5). TDF treatment was not associated with primary allograft failure at 3years post transplant after adjusting for DGF and a propensity score for TDF use (hazard ratio 2.12, 95% confidence interval 0.41-10.9). In a large single-center experience of HIV+ kidney transplantation, TDF use following kidney transplantation was not significantly associated with primary allograft failure. These results may help inform management for HIV+ KT recipients in need of TDF therapy for adequate viral suppression.

Kidney Transplantation Outcomes in HIV Infection: The European Experience

Kidney Transplantation Outcomes in HIV Infection: The European Experience

Renal Transplantation in HIV-Positive Recipients

About 1% of all patients with end-stage renal disease in the United States are infected with HIV. With the introduction of highly active antiretroviral therapy (HAART), HIV death rates have declined 80%, and chronic diseases resulting from HIV have replaced opportunistic infections as the leading cause of death among HIV-infected patients. Traditionally, HIV infection has been considered an absolute contraindication to solid-organ transplantation. However, in the context of improved survival, the role for kidney transplantation among HIV-positive patients is currently being revisited. This article discusses long-term outcomes after kidney transplantation in the HAART era and management strategies for the HIV-positive kidney transplant recipient.