HIV-positive Recipients Research Articles

Identification of Optimal Donor-Recipient Combinations Among Human Immunodeficiency Virus (HIV)-Positive Kidney Transplant Recipients.

For some patient subgroups, human immunodeficiency virus (HIV) infection has been associated with worse outcomes after kidney transplantation (KT); potentially modifiable factors may be responsible. The study goal was to identify factors that predict a higher risk of graft loss among HIV-positive KT recipients compared with a similar transplant among HIV-negative recipients. In this study, 82 762 deceased donor KT recipients (HIV positive: 526; HIV negative: 82 236) reported to the Scientific Registry of Transplant Recipients (SRTR) (2001-2013) were studied by interaction term analysis. Compared to HIV-negative recipients, the hepatitis C virus (HCV) amplified risk 2.72-fold among HIV-positive KT recipients (adjusted hazard ratio [aHR]: 2.72, 95% confidence interval [CI]: 1.75-4.22, p < 0.001). Forty-three percent of the excess risk was attributable to the interaction between HIV and HCV (attributable proportion of risk due to the interaction [AP]: 0.43, 95% CI: 0.23-0.63, p = 0.02). Among HIV-positive recipients with more than three HLA mismatches (MMs), risk was amplified 1.80-fold compared to HIV-negative (aHR: 1.80, 95% CI: 1.31-2.47, p < 0.001); 42% of the excess risk was attributable to the interaction between HIV and more than three HLA MMs (AP: 0.42, 95% CI: 0.24-0.60, p = 0.01). High-HIV-risk (HIV-positive/HCV-positive HLAwith more than three MMs) recipients had a 3.86-fold increased risk compared to low-HIV-risk (HIV-positive/HCV-negative HLA with three or fewer MMs)) recipients (aHR: 3.86, 95% CI: 2.37-6.30, p < 0.001). Avoidance of more than three HLA MMs in HIV-positive KT recipients, particularly among coinfected patients, may mitigate the increased risk of graft loss associated with HIV infection.

Renal Transplantation in HIV-positive Renal Transplant Recipients: Experience at the Mannheim University Hospital

Renal transplantation in HIV-positive patients with end-stage renal disease has in recent years become a successful treatment option. We report two patients who underwent renal transplantation using a combination of basiliximab, calcineurin inhibitors, mycophenolate mofetil (MMF), and steroids with a “non-interacting” antiretroviral combination therapy consisting of stavudine or abacavir, lamivudine, and nevirapine. We observed no acute rejection but a BK polyomavirus infection in both patients. In conclusion, a quadruple immunosuppression with an interleukin 2 receptor antagonist, a calcineurin inhibitor, MMF, and steroids appears to be advisable to prevent high rates of acute rejection, but if possible thereafter immunosuppression should be tapered rapidly (eg, MMF stop, prednisolone dose 5 mg/d). The selection of antiretroviral agents should avoid compounds that interact severely with the immunosuppression used.

Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls.

To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients. Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls. We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models. There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis. Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest. ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.

Drug induced alloreactivity: A new paradigm for allorecognition

Aim Abacavir administration is associated with drug induced hypersensitivity reactions in HIV patients expressing the HLA-B∗57:01 allele. However the immunological effects of abacavir administration in an HLA-B57 mismatched transplantation setting has not been studied. We hypothesized that abacavir exposure would induce de-novo HLA-B57 specific allorecognition. Methods Multiple HIV-specific CD8 T cell clones were generated from HIV infected patients negative for the HLA-B57 antigen, using single cell sorting based on HIV peptide/HLA tetrameric complex staining. The generated T cell clones were assayed for alloreactivity against a panel of single HLA expressing cell lines (SALs), in the presence or absence of abacavir. Cytokine assay, CD137 upregulation and cytotoxicity were used as readout. Results Abacavir exposure did induce de-novo HLA-B57 allorecognition by HIV-specific T cells. A Gag RK9/HLA-A3 specific T cell clone, from an HLA-B57 negative HIV patient, did recognize allogeneic HLA-B57 but only in the presence of abacavir. Abacavir did not induce recognition of any other allogeneic HLA molecules. Another clone from the same patient with the same specificity, but with different TCR Vb usage, did not recognize allogeneic HLA-B57 in the presence of abacavir, suggesting TCR Vb specificity of the drug induced allorecognition. Conclusion Results presented here provide the first evidence that administration of a drug could induce specific allorecognition of mismatched HLA molecules in the transplant setting. Furthermore, HIV-specific memory T cells themselves may participate in the abacavir induced alloreactivity. We suggest that HIV-positive recipients of a HLA-B57 mismatched graft should not receive abacavir until further studies are completed.

Kidney Rejection in HIV-Positive Recipients Is Associated With Immune Activation and Higher Frequency of Donor-Reactive CD8 Cells.

Background: HIV+ kidney transplant recipients have 3 times higher rejection rate when compared to HIV- recipients. Approximately half of those who have at least one rejection experienced a rejection episode within the first 30 days after transplant, suggesting that the enhanced rejection may be due to potent immune activation or preformed memory responses to donor alloantigens. Methods: We analyzed banked peripheral blood samples from HIV+ patients collected just before transplant and compared to HIV+ disease status-matched non-transplant and HIV- age-matched control subjects. We compared the total CD4+ cell counts in the blood and used multicolor flow cytometry to determine the frequency of effector and memory T cells. The frequencies of donor-alloantigen-reactive CD8+ T cells, conventional CD4+ T cells, and regulatory T cells were measured using an improved one-way mixed lymphocyte reaction assay. Results: CD4+ T cell counts in HIV+ pre-transplant patients were not significantly lower than HIV- pre-transplant patients, likely because of the preferential enrollment of healthiest HIV+ patients defined by the study entry eligibility criteria. HIV+ transplant patients had higher percentages of CD4+CD45RA-CCR7- effector cells when compared with age-matched HIV+ non-transplant and HIV- patients (27.2±2.3, 12.0±2.0, vs. 16.1±3.0; n=52, 10, 9; p=0.0023). However, no difference between rejector and non-rejector was noted. HIV+ rejectors had higher frequency of donor-reactive CD8+ T cells when compared to non-rejectors (4.46±0.79 vs. 2.26±0.58; n=8, 8; p=0.045); whereas frequencies of CD4+ conventional T cells and regulatory T cells were not significantly different between the rejectors and the non-rejectors. Conclusion: Our results thus far are consistent with the interpretation that HIV+ transplant recipients have more activated immune system. Higher frequency of donor-reactive CD8+ T cell pre-transplant may distinguish rejectors from non-rejectors.

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.

HIV outcomes in Hepatitis B virus coinfected individuals on HAART.

Understanding the impact of hepatitis B virus (HBV) coinfection on HIV outcomes in the highly active antiretroviral therapy (HAART) era continues to be a critical priority given the high prevalence of coinfection and the potential for impaired immunologic, virologic, and clinical recovery. Participants from the US Military HIV Natural History Study with an HIV diagnosis on HAART and serologically confirmed HBV infection status at HAART initiation (HI) were classified into 4 HBV infection (HB) groups. HIV virologic, immunologic, and clinical outcomes were evaluated by HB status. Of 2536 HIV-positive HAART recipients, with HBV testing results available to determine HB status in the HI window, HB status at HI was classified as HB negative (n = 1505; 66%), resolved HB (n = 518; 23%), isolated hepatitis B core antigen (n = 139; 6%), or chronic HB (n = 131; 6%). HIV virologic suppression and failure at 6 months or 1 year were not significantly different by HB status. A significantly faster rate of increase in CD4 cell count during the period between 4 and 12 years was observed for chronic HB relative to HB negative. Chronic and resolved HB were associated with an increased risk of AIDS/death compared with HB-negative individuals (chronic HB-hazard ratio = 1.68, 95% confidence interval: 1.05 to 2.68; resolved HB-hazard ratio = 1.61, 95% confidence interval: 1.15 to 2.25). HB status did not have a significant impact on HIV virologic outcomes, however, CD4 cell count reconstitution after HI and the risk of an AIDS event or death after HI may be associated with HB status.

Ethics of facial transplantation revisited

There have been 26 cases of facial transplantation reported, and three deaths, 11.5%. Mortality raises the issue of risk versus benefit for face transplantation, a procedure intended to improve quality of life, rather than saving life. Thus, one of the most innovative surgical procedures has opened the debate on the ethical, legal, and philosophical aspects of face transplantation. Morbidity in face transplant recipients includes infections and metabolic consequences. No graft loss caused by technical failure, hyperacute, or chronic graft rejection or graft-versus-host disease has been reported. One case of posttransplant lymphoproliferative disorder, 3.45% and one case of lymphoma in an HIV-positive recipient were reported. Psychological issues in candidates can include chronic pain, mood disorders, preexisting psychotic disorders, post-traumatic stress disorder (PTSD), and substance abuse. Early publications on ethical aspects of face transplantation focused mainly on informed consent. Many other ethical issues have been identified, including lack of coercion, donor family consent and confidentiality, respect for the integrity of the donor's body, and financial promotion of the recipient and transplant team, as well as the cost to society for such a highly technical procedure, requiring lifelong immunosuppression.

HIV RNA levels in plasma and cervical-vaginal lavage fluid in elite controllers and HAART recipients.

The introduction of HAART leads to control of HIV replication to less than 50 copies/ml, similar to levels in 'elite controllers'. Low-level viral replication may be one of the contributing factors to persistent immune activation/inflammation in HAART-treated individuals. There are still gaps in our knowledge of whether low-level replication persists in systemic versus mucosal sites. Participants for this study were recruited from the Women's Interagency HIV Study. We evaluated 33 'elite controllers' who naturally controlled HIV replication and 33 matched HAART-suppressed recipients. This study employed a sensitive target-capture transcription-mediated-amplification assay to compare low-level virus concentrations in plasma and cervical-vaginal lavage (CVL) samples from HIV-positive HAART recipients and 'elite controllers'. The median (interquartile range) plasma viral load signal/cut-off (S/Co) for 'elite controllers' was 10.5 (3.9-21.1), which was significantly (P < 0.001) higher than the S/Co for HAART recipients [2.0 (1-4.9)]. The majority of CVL samples from both groups had undetectable HIV RNA and the proportion of CVL samples with a cut-off more than 1.0 was not different between 'elite controllers' and HAART-suppressed recipients. This study demonstrated persistent low-level HIV replication in 'elite controllers', suggesting potential value of HAART treatment for these individuals. Absent or very low levels of HIV RNA in CVL indicate very low risk of secondary sexual transmission for both groups.

Management of Immunosuppression and Antiviral Treatment before and after Heart Transplant for HIV-Associated Dilated Cardiomyopathy

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.

Vitamin D status of human immunodeficiency virus-positive patients with advanced liver disease enrolled in the solid organ transplantation in HIV: Multi-site study

An optimal vitamin D status may benefit liver transplantation (LT) patients. Higher levels of 25-hydroxyvitamin D [25(OH)D] mitigate steroid-induced bone loss after LT, correlate with better hepatitis C virus treatment responses, and increase graft survival. This study investigated 25(OH)D levels and assessed strategies for vitamin D deficiency prevention in human immunodeficiency virus (HIV)–positive patients with advanced liver disease who were enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study. 25(OH)D was measured in banked specimens from 154 LT candidates/recipients with the DiaSorin assay; deficiency was defined as a 25(OH)D level < 20 ng/mL. Information about vitamin D supplement use after LT was obtained from medication logs and via surveys. Logistic regression, Cox regression, and linear repeated measures analyses were performed with SAS software. We found that none of the 17 academic medical centers in the United States routinely recommended vitamin D supplements before LT, and only a minority (4/17) recommended vitamin D supplements to all patients after LT. Seventy-one percent of the 139 patients with pre-LT values had vitamin D deficiency, which was significantly associated with cirrhosis (P = 0.01) but no other variable. The vitamin D status improved modestly after LT; however, the status was deficient for 40% of the patients 1 year after LT. In a multivariate linear repeated measures model, a higher pre-LT 25(OH)D level (P < 0.001), specimen collection in the summer (P < 0.001), a routine vitamin D supplementation strategy after LT (P < 0.001), and the time elapsing since LT (P = 0.01) were significantly associated with increases in the post-LT 25(OH)D level; black race was associated with a decreased level (P = 0.02). In conclusion, the majority of patients awaiting LT were vitamin D deficient, and approximately half were vitamin D deficient after LT. More extensive use of vitamin D supplements, more sun exposure, or both are needed to prevent this deficiency in HIV-positive LT candidates and recipients. Liver Transpl 20:156-164, 2014. © 2013 AASLD.

Acquired hypogammaglobulinemia in HIV‐positive subjects after liver transplantation

As more solid organ transplantations are performed in patients infected with human immunodeficiency virus (HIV), post-transplant complications in this population are becoming better defined. Using serum samples from the Solid Organ Transplantation in HIV: Multi-Site Study, we studied the epidemiology of acquired hypogammaglobulinemia (HGG) after liver transplantation (LT) in 79 HIV-infected individuals with a median CD4 count at enrollment of 288 (interquartile range 200-423) cells/μL. Quantitative immunoglobulin G (IgG) levels before and after LT were measured, with moderate and severe HGG defined as IgG 350-500 mg/dL and <350 mg/dL, respectively. Incidence, risk factors, and associated outcomes of moderate or worse HGG were evaluated using Kaplan-Meier estimator and proportional hazards (PH) models. The 1-year cumulative incidence of moderate or worse HGG was 12% (95% confidence interval [CI]: 6-22%); no new cases were observed between years 1 and 2. In a multivariate PH model, higher pre-transplant model for end-stage liver disease score (P = 0.04) and treated acute rejection (P = 0.04) were both identified as significant predictors of moderate or worse HGG. There was a strong association of IgG levels <500 mg/dL with non-opportunistic serious infection (hazard ratio [95% CI]: 3.5 [1.1-10.6]; P = 0.03) and mortality (3.2 [1.1-9.4]; P = 0.04). These associations held after adjustment for important determinants of infection and survival among the entire cohort. These results suggest that a proportion of HIV-positive LT recipients will develop clinically significant HGG after transplantation.

Does increased hepatitis B vaccination dose lead to a better immune response in HIV-infected patients than standard dose vaccination: a meta-analysis?

Human immunodeficiency virus (HIV)-infected patients often fail to produce protective antibodies to hepatitis B virus (HBV) vaccine. Some reports have suggested that increased-dose vaccination improves immune response to HBV vaccine in HIV-infected patients. To assess the efficacy of increased-dose HBV vaccination in HIV-infected patients, a systematic review of the literature and meta-analysis of clinical trials was conducted. We only included trials that compared the response rate at completion of HBV vaccine schedules in patients who had increased-dose HBV vaccine courses with controls (standard-dose HBV vaccine vaccination schedule). The fixed-effects model, with heterogeneity and sensitivity analyses, was used in this study. We identified five studies involving 883 HIV-positive vaccine recipients. Pooling of study results showed a significant increase in response rates among high-dose patients versus control patients; the pooled odds ratio (OR) was 1.96 (95% confidence interval [CI]: 1.47; 2.61). Four out of five identified studies included only vaccine-naive patients. The overall OR was 1.82 (95% CI: 1.35-2.47). No study heterogeneity was found. Our meta-analysis showed that increasing the dosage of vaccine may significantly improve immune responses in HIV-infected patients.

High Frequency of Rejections in HIV-Positive Recipients of Kidney Transplantation

This is a single institution report of the incidence of combined acute antibody-mediated rejection (ABMR) + acute cellular rejection (ACR) [mixed rejection] in HIV (+) kidney transplant recipients. We prospectively enrolled 92 HIV (+) patients who received a kidney transplant between 2001 and 2009. There were three cohorts: no rejection [n=26], ACR [n=53], and mixed rejections (ABMR and ACR) [n=13]. Immunosuppression comprised of basiliximab, cyclosporine, sirolimus, and steroid minimization. Fisher exact tests for categorical variables, t test for continuous variables, and Kaplan-Meier estimates were used to describe events. Mixed rejections were seen in all 13 HIV (+) kidney transplant recipients (14%) with a median time to ABMR of 48 days. Acute cellular rejection occurred in 28% at 1 month and 55% at 12 months. eGFR was lower for recipients who experienced ABMR versus those experiencing ACR and those never experiencing rejection up to 3 years (14 ± 9.4 vs 19 ± 3.3 vs 29 ± 7.3 mL/min, respectively). Kaplan-Meier showed that graft survival up to 9 years was worse in recipients experiencing mixed rejection. Suboptimal donors with terminal creatinine greater than 2.5 mg/dL was associated with increased incidence of mixed rejections versus cellular rejections and no rejection (42% vs 17% vs. 8%, respectively). Our single center study showed a relatively higher incidence of mixed rejection compared with that reported for non-HIV transplant recipients. A donor terminal serum creatinine greater than 2.5 mg/dL predicted mixed rejection, which was associated with poor outcomes. Donor selection and optimization of immunosuppression may be critical in these patients.

Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant.

BackgroundThe Infectious Disease Society of America (IDSA) 2010 Clinical Practice Guidelines for the management of cryptococcosis outlined three key populations at risk of disease: (1) HIV-infected, (2) transplant recipient, and (3) HIV-negative/non-transplant. However, direct comparisons of management, severity and outcomes of these groups have not been conducted.Methodology/Principal FindingsAnnual changes in frequency of cryptococcosis diagnoses, cryptococcosis-attributable mortality and mortality were captured. Differences examined between severe and non-severe disease within the context of the three groups included: demographics, symptoms, microbiology, clinical management and treatment. An average of nearly 15 patients per year presented at Duke University Medical Center (DUMC) with cryptococcosis. Out of 207 study patients, 86 (42%) were HIV-positive, 42 (20%) were transplant recipients, and 79 (38%) were HIV-negative/non-transplant. HIV-infected individuals had profound CD4 lymphocytopenia and a majority had elevated intracranial pressure. Transplant recipients commonly (38%) had renal dysfunction. Nearly one-quarter (24%) had their immunosuppressive regimens stopped or changed. The HIV-negative/non-transplant population reported longer duration of symptoms than HIV-positive or transplant recipients and 28% (22/79) had liver insufficiency or underlying hematological malignancies. HIV-positive and HIV-negative/non-transplant patients accounted for 89% of severe disease cryptococcosis-attributable deaths and 86% of all-cause mortality.Conclusions/SignificanceIn this single-center study, the frequency of cryptococcosis did not change in the last two decades, although the underlying case mix shifted (fewer HIV-positive cases, stable transplant cases, more cases with neither). Cryptococcosis had a relatively uniform and informed treatment strategy, but disease-attributable mortality was still common.

Is it justifiable to transplant infected livers into haemophilia recipients?

Is it justifiable to transplant infected livers into haemophilia recipients?

Pap testing among newly diagnosed women living with HIV/AIDS (WLWHA) in South Carolina (SC): routine screening and abnormal follow-up behaviors of HIV-positive female SC medicaid recipients 18-64 years between 2005-2009

Background Oncogenic human papillomavirus (HPV) infection is a main cause of cervical cancer. HIV-positive women are at an increased risk of becoming infected with high risk HPV (hrHPV) types that can lead to cervical cancer. Unlike other AIDS defining cancers, such as Kaposi’s sarcoma and Hodgkin’s lymphoma, the incidence of invasive cervical cancer among WLWHA has not decreased with the arrival of highly active antiretroviral therapies (HAART). [1,2] Annual Pap tests are recommended for WLWHA because the risk of developing cervical cancer, an AIDS defining illness, is increased in this group.[3] Early detection of abnormal, precancerous cells and following up on abnormal cytology results is essential to the prevention and control of cervical cancer among WLHWA.

Report of Four Simultaneous Pancreas–Kidney Transplants in HIV-Positive Recipients With Favorable Outcomes

The advent of combined antiretroviral therapy (cART) dramatically changed the view of human immunodeficiency virus (HIV) infection as an exclusion criterion for solid organ transplantation, resulting in worldwide reports of successful transplants in HIV-infected individuals. However, there are few reports on simultaneous pancreas-kidney transplant in HIV-positive recipients detailing poor outcomes. A series of four pancreas-kidney transplant performed on HIV-infected individuals between 2006 and 2009 is presented. All recipients reached stably undetectable HIV-RNA after transplantation. All patients experienced early posttransplant infections (median day 30, range 9-128) with urinary tract infections and bacteremia being most commonly observed. In all cases, surgical complications led to laparotomic revisions (median day 18, range 1-44); two patients underwent cholecystectomy. One steroid-responsive acute renal rejection (day 79) and one pancreatic graft failure (month 64) occurred. Frequent dose adjustments were required due to interference between cART and immunosuppressants. At a median follow-up of 45 months (range, 26-67) we observed 100% patient survival with CD4 cell count >300 cells/mm(3) for all patients. Although limited by its small number, this case series represents the largest reported to date with encouraging long-term outcomes in HIV-positive pancreas-kidney transplant recipients.

Human immunodeficiency virus-infected patients undergoing liver transplantation are at high risk of vascular complications: True or not?

We read with interest the article recently published by Cherian et al.1 in Liver Transplantation. The authors presented a series of 24 liver transplants in human immunodeficiency virus (HIV)–positive recipients and focused on vascular complications. They reported that 8 of the 24 patients (33%) suffered a vascular complication; precisely 5 (20%) had hepatic artery thrombosis (HAT), 1 (4%) had a generalized arteriopathy (according to angiography), and 1 (4%) had endoarteritis (according to a histological analysis). Multiple arterial anastomoses were created in 8 of the 24 recipients, and 2 cases of HAT occurred in this group. The authors did not mention how many patients had undergone an aortohepatic bypass. In addition, 5 separate venous thrombotic events were detected in the 24 recipients. These data compared unfavorably with their experience with HIV-negative cases (ie, a 2.7% incidence of HAT among more than 2000 adult recipients over a 15-year period). The authors concluded that the prothrombotic state associated with the combination of HIV and liver disease was a cause of post-LT morbidity, in that 8 of the 24 recipients (33%) suffered a vascular thrombotic complication. Moreover, according to Cherian et al., there was a potential increase in the risk of HAT in the HIV-positive cohort versus the HIV-negative historical controls [3.2% versus 12%, P = 0.016 (Fisher's exact test)]. They suggested that multiple acquired and persistent thrombophilic abnormalities, such as protein C and S deficiencies and increased factor VIII concentrations, which are more frequently observed in HIV-infected patients versus healthy populations, might be a possible explanation for the high incidence of vascular complication in this HIV series.2, 3 The results reported for this series are not in accordance with the experience with liver transplantation in HIV-infected patients at our center. From 2004 to 2011, we performed liver transplantation for 32 HIV-positive patients. No cases of HAT were encountered. Vascular complications included 2 cases of early hepatic artery stenosis (within 30 days after transplantation) successfully treated with percutaneous transluminal angioplasty (PTA) and stenting, 1 case of early portal vein thrombosis (day 1) successfully treated with surgical thrombectomy, and 1 case of late hepatic vein stenosis (6 months after transplantation) successfully treated with PTA and stenting. The overall incidence was 12.5%. No separate venous thrombotic events were detected in our series. An aortohepatic bypass was used in 5 cases (15.6%); 4 patients received full right split liver grafts with an arterial anastomosis on the right hepatic artery. Complex arterial reconstructions at the back table were performed in 5 cases (15.6%). At a median follow-up of 33 months (range = 9-85 months), the resistive index of the hepatic artery according to color Doppler ultrasound was 0.64 ± 0.07; no cases of HAT were encountered, and this included 2 cases of arterial stenosis treated with PTA and stenting. Our posttransplant thrombotic prophylaxis policy consisted of low-molecular-weight heparin for 10 days followed by long-term anti-aggregation therapy with 100 mg of acetylsalicylic acid daily, and it did not differ from the policy for non-HIV cases. Historically, the incidence of HAT at our center has been 4.4%,4 which is perfectly within the range reported in the literature (1.6%-8%).5 In conclusion, according to our experience, liver transplantation for HIV-positive recipients is not associated with a higher incidence of any type of vascular complication and is especially not associated with HAT. Umberto Baccarani M.D. Ph.D. F.E.B.S.*, Stefania Bidinost M.D.*, Marcello Tavio M.D. , Pierluigi Viale M.D. , Gian Luigi Adani M.D., Ph.D.*, * Liver Transplant Unit Department of Medical and Biological Sciences University Hospital of Udine Udine, Italy, Infectious Disease Unit Hospital of Ancona Ancona, Italy, Institute of Infectious Diseases University Hospital of Bologna Bologna, Italy.

Renal transplantation between HIV-positive donors and recipients justified

HIV infection was previously an absolute contraindication to renal transplantation. However, with the advent of highly active antiretroviral therapy (HAART), renal transplantation using HIV-negative donor kidneys has successfully been employed for HIV-infected patients with end-stage renal failure. In resource-limited countries, places on dialysis programmes are severely restricted; HIV-infected patients, like many others with co-morbidity, are often denied treatment. Kidneys (and other organs) from HIV-infected deceased donors are discarded. The transplantation of HIV-positive donor kidneys to HIV-infected recipients is now a viable alternative to chronic dialysis or transplantation of HIV-negative donor kidneys. This significantly increases the pool of donor kidneys to the advantage of HIV-positive and -negative patients. Arguments are presented that led to our initiation of renal transplantation from HIV-positive deceased donors to HIV-positive recipients at Groote Schuur Hospital, Cape Town.