HIV-infected Kidney Transplant Recipients Research Articles

Deciphering the True Immunologic Risk in Renal Transplantation in Patients With HIV

Since 1995, rates of end-stage renal disease have risen dramatically in patients living with HIV infection. However, given the concern for higher rates of acute rejection in this patient population, the immunologic threat posed by HIV infection is a specter clinicians must continually confront. Living donor transplantation may negate this risk; this study aims to assess the benefit of living donor transplantation in this population and to ascertain the immunologic risk faced by patients who are HIV-infected. The 2021 UNOS database was queried, and all HIV-infected kidney transplant recipients since 1987 were identified. Recipients were stratified based on deceased (DDKT) vs living (LDKT) donor status. Overall survival, allograft survival, acute rejection, panel reactive antibody (PRA) percentage, and crossmatch positivity were compared between groups. One thousand two hundred twenty-six patients underwent DDKT, and 304 patients underwent LDKT. Living donor kidney transplantation demonstrated greater overall survival (P=.045) and graft survival (P < .001). However, no difference in acute rejection was noted between the cohorts, and no difference in overall or graft survival was evident based on PRA percentage. Crossmatch positive status did not negatively affect graft survival. Patients with HIV undergoing LDKT fared better than those undergoing DDKT. Nevertheless, patients at higher immunologic risk-elevated PRA% and crossmatch positivity-did not experience graft loss at a higher rate than patients at lower immunologic risk. These results were valid in both DDKT and LDKT cohorts. These findings suggest that infection with HIV does not overtly increase patients' immunologic risk, and concerns surrounding transplantation in this population may be overestimated.

Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients.

Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking. We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival. Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively. rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRβ repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRβ clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

Importance of multidisciplinary collaboration for smooth kidney transplantation in HIV-infected patients with chronic kidney disease: a case report

BackgroundAntiretroviral therapy (ART) has reduced mortality caused by AIDS resulting from HIV infection. Meanwhile, the prevalence of chronic kidney disease, a chronic HIV complication, is increasing. Antiretroviral therapy has improved the life expectancy of HIV-infected kidney transplant recipients. In Japan, discrimination and prejudice against HIV persist, and few kidney transplants are performed. We report three cases in which kidney transplantation was smoothly performed with multidisciplinary collaboration.Case presentationThe first case involved a 29-year-old male urgently hospitalized due to severe kidney dysfunction, diagnosed with HIV-associated nephropathy (HIVAN), and placed on maintenance dialysis. The patient was administered oral lamivudine, abacavir, and raltegravir as ART and underwent blood group-matched living donor kidney transplantation at age 32. The second case involved a 49-year-old male diagnosed as HIV-positive at age 33 and placed on maintenance dialysis for HIVAN at age 47. Darunavir, ritonavir, and dolutegravir (DTG) were initially administered. However, the ART was switched to rilpivirine (RPV) and DTG prior to kidney transplantation because of potential ART interactions with calcineurin inhibitors. The patient underwent blood group-matched living donor kidney transplantation. The third case involved a 41-year-old male diagnosed as HIV-positive at 23 years old and treated with RPV and DTG. Due to autosomal dominant polycystic kidney disease (ADPKD), his kidney function gradually worsened, and he was started on hemodialysis. He underwent hemodialysis, followed by blood type-matched living donor kidney transplantation. In all cases, transplant physicians, nephrologists, infectious disease physicians, hepatologists, nurses, pharmacists, nutritionists, and clinical psychologists collaborated to discuss and share medical problems and sociopsychological backgrounds of the patients. There was no rejection, CD4+ lymphocyte counts were maintained, and there was no increase in viral load post-surgery. Information sharing among various departments has continued post-surgery, kidney function has improved, and no increase in viral load has been identified on follow-up.ConclusionsKidney transplantation is the kidney replacement therapy of choice for HIV-infected patients with CKD. Specialized support is required for kidney transplantation, including coordinating immunosuppressive therapy to avoid rejection, learning about drug interactions, and providing sociopsychological support. Multidisciplinary collaboration is important to ensure safe and smooth kidney transplantation care for HIV-infected patients.

Early steroid withdrawal in HIV-infected kidney transplant recipients: Utilization and outcomes.

Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P<.001). AR was more common with ESW by 1year (18.4% vs 12.3%; aOR: 1.08 1.612.41 , P=.04) and over the study period (aHR: 1.02 1.391.90 , P=.03), without difference in death-censored graft failure (aHR 0.60 0.911.36 , P=.33) or mortality (aHR: 0.75 1.151.77 , P=.45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable.

Role of Maraviroc in minimizing the risk ofgraft rejection in HIV-infected kidney transplant recipients.

Kidney transplantation in HIV-infected patients is characterized by a concerning high rate of allograft rejections. The etiological mechanisms leading to this increased immunoreactivity are still unknown. Maraviroc is a new antiretroviral agent that has been associated with immunomodulatory proprieties; therefore, its use may be a promising strategy to minimize the rate of rejections in HIV-infected kidney transplant (KT) recipients. We conducted a retrospective study in our cohort of HIV-KT recipients with the aim to explore the effects of maraviroc in reducing the risk of graft rejection. Twenty-two HIV-infected KT recipients predominantly of Caucasian origin (86%) and with a median age of 49 (IQR, 51.9-42.2) years were evaluated. Ten HIV-infected patients were treated with maraviroc and 12 with a maraviroc-free antiretroviral regimen. After a median follow-up of 3.01years, half of the maraviroc-treated patients (n=5) developed seven episodes of graft rejection, most of them were T cell-mediated rejections (85.7%). Five episodes were recorded in the maraviroc-free group. The difference in the rate of graft rejections was not statistically significant (P=.23). The administration of maraviroc was ineffective in preventing graft rejections in our cohort of patients.

Higher rates of rejection in HIV-infected kidney transplant recipients on ritonavir-boosted protease inhibitors: 3-year follow-up study.

Rejection rates in HIV-infected kidney transplant (KTx) recipients are higher than HIV-negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug-drug interactions, likely influencing outcomes. This is an IRB-approved, single-center, retrospective study of adult HIV-infected KTx patients between 5/2009 and 12/2014 with 3-year follow-up, excluding antibody-depleting induction. A total of 42 patients were included; median age was 52years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre-transplant dialysis. All patients received IL-2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir-boosted PI-based HAART (rtv+) regimen. Patient and graft survival at 3years were 93% and 90%. At 1-, 2-, and 3-year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy-proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P=0.029), 59% vs 24% (P=0.029), and 68% vs 24% (P=0.01). Despite higher rejection rates, HIV-infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.

Higher Rates of Rejection in HIV-infected Kidney Transplant Recipients on Ritonavir-Boosted Protease Inhibitors-Three-Year Follow Up

Background One-year rejection rates in HIV-infected kidney transplant recipients range from 15-40%, compared to overall rejection rates of 10% in HIV-negative patients. Protocols for immunosuppression and highly active antiretroviral therapy (HAART) vary substantially and there is potential for significant drug-drug interactions, specifically between ritonavir-boosted protease inhibitors (rtv+ PI) and calcineurin inhibitors. Methods This is an IRB-approved, single center, retrospective study of adult HIV-infected patients who underwent a kidney transplantation between 5/2009 to 12/2014 with a three-year follow up for each patient. Results Forty-two patients were identified with a median age of 52 (47, 57) years. Of these, 81% were male and 50% were African American, 29% were Hispanic, and 17% were Caucasian. The most common cause of renal failure was hypertensive nephrosclerosis (50%) followed by HIV-associated nephropathy (14%), and the median duration of pre-transplant dialysis was 5.8 (2.8, 8.7) years. All patients were induced with IL-2 receptor antagonist (IL-2 RA): 83% with basiliximab and 17% with daclizumab induction. Calcineurin inhibitor therapy included tacrolimus (76%), cyclosporine (17%), or transitions between these two (7%). 40% of patients received a rtv+ PI-based HAART regimen. At 30 days, patient and graft survival were 100%. Patient and graft survival were consistent at 93% and 90%, respectively, at years one, two, and three. Overall treated biopsy-proven rejection rates at one, two, and three years were 38%, 38%, and 41%, respectively, and 92% of these episodes were acute rejection. At one, two, and three years, rejection rates were significantly higher for recipients on rtv+PI compared to those on other HAART regimens as 59% vs 24% (p=0.029), 59% vs 24% (p=0.029), and 68% vs 24% (p=0.01), respectively. Conclusion HIV-infected kidney transplant recipients maintain excellent outcomes despite higher rates of acute rejection relative to HIV negative recipients. Given the significantly higher rates of rejection at one, two, and three years in the rtv + PI group, alternative HAART regimens should be considered prior to transplant when possible.

Infectious complications in HIV-infected kidney transplant recipients.

Renal transplantation is now a viable alternative for dialysis in HIV-infected patients who achieve good immunovirological control with current antiretroviral therapy regimens available. However, there are few studies that analyze the incidence of post-transplant infections in this population. In this study, a retrospective analysis of data files of 24 HIV-infected kidney transplant (KT) recipients was undertaken, matched to 21 non-infected controls. All patients received induction with anti-interleukin-2 antibodies and were followed in the Pitié-Salpêtrière Hospital in Paris, France. The rate of incidence of post-transplant infections was 23.58 and 26.98/100 patient-years, in HIV-infected and HIV-negative groups (relative risk [RR]: 0.90; 95% confidence interval [CI]: 0.58-1.39; p = 0.63). In HIV-infected KT recipients, bacterial infections were the most frequent (67.7%), followed by viral (14.7%) and fungal and parasitic infections (8.8%). Similar trends were seen in the control group. Incidence of opportunistic infections was similar in HIV-infected KT recipients and controls (38.2 vs. 26.5%; p = 0.44). There were three post-transplant HIV reactivations in two patients, secondary to poor adherence to medication. HIV status did not influence survival, but infections increased the risk of unfavorable outcome. Incidence of post-transplant infections was similar in HIV-infected KT recipients and controls. Infections, but not HIV status, had adverse effects on patient and graft survival.

Renal transplantation in human immunodeficiency virus‐infected recipients: a case–control study from the Brazilian experience

Highly active antiretroviral therapy has turned human immunodeficiency virus (HIV)-infected patients with end-stage renal disease into suitable candidates for renal transplantation. We present the Brazilian experience with kidney transplantation in HIV-infected recipients observed in a multicenter study. HIV-infected kidney transplant recipients and matched controls were evaluated for the incidence of delayed graft function (DGF), acute rejection (AR), infections, graft function, and survival of patients and renal grafts. Fifty-three HIV-infected recipients and 106 controls were enrolled. Baseline characteristics were similar, but a higher frequency of pre-transplant positivity for hepatitis C virus and cytomegalovirus infections was found in the HIV group. Immunosuppressive regimens did not differ, but a trend was observed toward lower use of anti-thymocyte globulin in the group of HIV-infected recipients (P = 0.079). The HIV-positive recipient group presented a higher incidence of treated AR (P = 0.036) and DGF (P = 0.044). Chronic Kidney Disease Epidemiology Collaboration estimated that glomerular filtration rate was similar at 6 months (P = 0.374) and at 12 months (P = 0.957). The median number of infections per patient was higher in the HIV-infected group (P = 0.018). The 1-year patient survival (P < 0.001) and graft survival (P = 0.004) were lower, but acceptable, in the group of HIV-infected patients. In the Brazilian experience, despite somewhat inferior outcomes, kidney transplantation is an adequate therapy for selected HIV-infected recipients.

A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients.

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002-2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)-negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.

Tacrolimus Exposure and Its Relation With Clinical Outcomes in HIV Infected Kidney Transplant Recipients On Antiretroviral Agents: An Area-Under-The-Curve Driven Analysis.

Tacrolimus Exposure and Its Relation With Clinical Outcomes in HIV Infected Kidney Transplant Recipients On Antiretroviral Agents: An Area-Under-The-Curve Driven Analysis.

Low Incidence of Opportunistic Infections in HIV Infected Kidney Transplant Recipients Who Recieved Lymphocyte Depleting Induction Therapy.

Low Incidence of Opportunistic Infections in HIV Infected Kidney Transplant Recipients Who Recieved Lymphocyte Depleting Induction Therapy.

Long-Term Outcomes Among HIV-Infected Kidney Transplant Recipients.

Long-Term Outcomes Among HIV-Infected Kidney Transplant Recipients.

Choice of Induction in HIV-Infected Kidney Transplant Recipients and Its Impact On Transplant Outcomes.

Purpose: The introduction of highly active antiretroviral therapy (HAART) has made kidney transplantation among HIV-infected patients possible. Despite the improvement in overall transplant outcomes, the incidence of acute cellular rejection (AR) in this population is high. The reasons for this have not been fully studied. We sought to examine the association of induction agent with AR and graft outcomes in these patients. Methods: From 2003 to 2013, our institution performed 45 renal transplants in HIV-infected individuals. 34 (75.6%) patients received basiliximab (BSX) and 11 (24.4%) received lymphocyte depleting (LD) agents. Mean follow up time were (43 ± 24) months in BSX and (15 ± 7) months in LD group. Results: Patient and transplant-related characteristics are summarized in Table 1.Table: No Caption available.Graft function, evidenced by SCr, was similar between groups at 3 months (1.79 ± 0.74 vs 2.09 ± 1.4, p = 0.36), 6 months (1.89 ± 1.41 vs 2.28 ± 1.94, p = 0.49), and 1 year (1.97 ± 1.38 vs 2.15 ± 1.59, p = 0.11). AR rates were similarly high in both groups.Figure: No Caption available.There were 10 (29.4%) graft losses in the BSX and 3 (27.2%) in the LD group. 5 patients in the BSX group (14.7%) and none in the LD group died during the follow up period (P=0.3). Conclusions: Our study showed a relatively high incidence of acute cellular rejection in HIV-positive renal transplant recipients. The choice of induction agent did not impact acute rejection rate, allograft function, and patient or graft survival.

Reduction of HIV Persistence Following Transplantation in HIV-Infected Kidney Transplant Recipients

Chronic inflammation may contribute to human immunodeficiency virus (HIV) persistence through a number of potential pathways. We explored the impact of immunosuppressant therapy on peripheral blood measures of HIV persistence following kidney transplantation. Stored plasma and peripheral blood mononuclear cells prior to transplantation and at weeks 12, 26, 52 and 104 posttransplant were obtained from 91 transplant recipients. In a multivariate model, higher pretransplant plasma HIV RNA level (p < 0.0001) and a longer duration of follow-up posttransplant (p = 0.09) were associated with higher posttransplant plasma HIV RNA levels. A higher baseline HIV DNA (p < 0.0001) was significantly associated with higher HIV DNA levels posttransplant, while higher CD4+ T cell count (p = 0.001), sirolimus use (p = 0.04) and a longer duration of follow-up (p = 0.06) were associated with lower posttransplant HIV DNA levels. The association between sirolimus exposure and lower frequency of cells containing HIV DNA levels posttransplant suggest that the immune-modifying drugs may affect the level of HIV persistence during effect therapy. Future studies of sirolimus as a reservoir-modifying agent are warranted.

Best Single Time Point Correlations With AUC for Cyclosporine and Tacrolimus in HIV-Infected Kidney and Liver Transplant Recipients

Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, tacrolimus (TAC) trough levels (C0) or cyclosporine (CsA) drawn at C0 or 2 hours after dosing (C2) correlate with drug exposure (area under the curve [AUC]/dose) and outcomes. Because of ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, this study investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels. This study prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS in 150 studies over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with liquid chromatography-tandem mass spectrometry and AUC calculated using WinNonlin 9.0. Correlation analyses were run on SAS 9.2. CsA concentration at C4 correlated better with AUC than C0 or C2, and over time TAC concentration correlated better at C0 or C2. It is suggested that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.

Immunosuppression Regimen and the Risk of Acute Rejection in HIV-Infected Kidney Transplant Recipients

Kidney transplantation (KT) is the treatment for end-stage renal disease in appropriate HIV-positive individuals. However, acute rejection (AR) rates are over twice those of HIV-negative recipients. To better understand optimal immunosuppression for HIV-positive KT recipients, we studied associations between immunosuppression regimen, AR at 1 year, and survival in 516 HIV-positive and 93,027 HIV-negative adult kidney-only recipients using Scientific Registry of Transplant Recipients data from 2003 to 2011. Consistent with previous reports, HIV-positive patients had twofold higher risk of AR (adjusted relative risk [aRR], 1.77; 95% confidence interval [CI], 1.45-2.2; P<0.001) than their HIV-negative counterparts as well as a higher risk of graft loss (adjusted hazard ratio, 1.51; 95% CI, 1.18-1.94; P=0.001), but these differences were not seen among patients receiving antithymocyte globulin (ATG) induction (aRR for AR, 1.16; 95% CI, 0.41-3.35, P=0.77; adjusted hazard ratio for graft loss, 1.54; 95% CI, 0.73-3.25; P=0.26). Furthermore, HIV-positive patients receiving ATG induction had a 2.6-fold lower risk of AR (aRR, 0.39; 95% CI, 0.18-0.87; P=0.02) than those receiving no antibody induction. Conversely, HIV-positive patients receiving sirolimus-based therapy had a 2.2-fold higher risk of AR (aRR, 2.15; 95% CI, 1.20-3.86; P=0.01) than those receiving calcineurin inhibitor-based regimens. These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

High incidence of delayed graft function in HIV-infected kidney transplant recipients

Kidney transplantation (KT) outcomes in human immunodeficiency virus (HIV)-infected recipients are under continuous research. High incidence of early post-transplant complications such as acute rejection has been observed. A multicenter study including HIV-infected patients who underwent KT in Spain, from 2001 to 2011, was performed. The study population included 108 recipients, 36 HIV-infected, and 72 matched HIV-negative KT recipients. HIV-infected recipients developed more delayed graft function (DGF) (52% vs. 21%, P < 0.001). One- and 3-year graft survival was 91.6% and 86.2% in HIV-infected patients, and 97.1% and 94.7% in HIV-negative patients (P = 0.052). In two-variate Cox analysis, HIV infection was not a predictor of graft loss after adjusting for time on dialysis, acute rejection, and DGF. Multivariate analysis for DGF revealed HIV-positive status as independent risk factor. We analyzed the evolution of immunosuppressive and antiretroviral therapy (ART). In HIV-infected patients tacrolimus trough levels were very high in the first week and significantly lower in the second week post-transplant (P = 0.042). Post-transplant ART was significantly changed: protease inhibitors use decreased (P = 0.034) and integrase inhibitor use increased (P < 0.001). DGF is another frequent early complication in HIV-infected recipients that can affect graft survival. Strategies to prevent DGF and antiretroviral regimes with less drug interactions could improve outcomes.

HIV-Infected Kidney Graft Recipients Managed With an Early Corticosteroid Withdrawal Protocol

The outcome of HIV-infected kidney transplant recipients managed with an early corticosteroid withdrawal protocol is not known. Eleven consecutive HIV-infected patients with undetectable plasma HIV RNA and more than 200/mm CD4 T cells underwent deceased-donor (n=8) or living-donor (n=3) kidney transplantation at our center. All were managed with an early corticosteroid withdrawal protocol; 9 of 11 received antithymocyte globulin and 2 received basiliximab induction. We analyzed patient and graft outcomes, acute rejection rate, HIV progression, BKV replication, infections, and urinary cell mRNA profiles. The median (range) follow-up was 44.5 (26-73) months. The incidence of acute rejection was 9% at 1 year and the patient and allograft survival rates were 100% and 91%, respectively. Estimated glomerular filtration rate at 1 year (mean ± SD) was 78 ± 39 mL/min/1.73 m. Plasma HIV RNA was undetectable at 24 months and none had BKV replication. Six of the 11 kidney recipients developed eight infections requiring hospitalization. Urinary cell levels of mRNA for complement components and complement regulatory proteins, cell lineage-specific proteins CD3, CD4, CD8, CTLA4, Foxp3, chemokine IP-10, cytotoxic perforin and granzyme B, and BKV VP1 mRNA were not different (P>0.05) between HIV-infected patients and HIV-negative recipients (n=22) with stable graft function and normal biopsy results. An early steroid withdrawal regimen with antithymocyte globulin induction was associated with excellent graft and patient outcomes in HIV-infected recipients of kidney allografts. Their urinary cell mRNA profiles are indistinguishable from those of HIV-negative patients with stable graft function and normal biopsy results.