Curr Infect Dis Rep (2013) 15:526–535 DOI 10.1007/s11908-013-0381-x

TRANSPLANT AND ONCOLOGY (M ISON AND N THEODOROPOULOS, SECTION EDITORS)

Organ Transplantation in HIV Patients: Current Status and New Directions Valentina Stosor

Published online: 20 October 2013 # Springer Science+Business Media New York 2013

Abstract Combination antiretroviral therapy has resulted in longer life expectancies in persons living with HIV; however, end organ disease and death from organ failure have become growing issues for this population. With effective therapies for viral suppression, HIV is no longer considered an absolute contraindication to organ transplantation. Over the past decade, studies of transplantation in patients with HIV have had encouraging results such that patients with organ failure are pursuing transplantation. This review focuses on the current status of organ transplantation for HIV-infected persons. Keywords Human immunodeficiency virus . Acquired immunodeficiencysyndrome . Hepatitis C infection . Hepatitis B infection . Organ transplantation . Kidney transplantation . Liver transplantation . Hematopoietic stem cell transplantation . Heart transplantation . Mechanical circulatory support . Pancreas transplantation . Lung transplantation

Introduction Nearly 2 decades ago, highly active therapies for HIV infection became available, and soon after their introduction, dramatic reductions of AIDS-defining conditions and mortality were observed [1]. The sustained benefit of antiretroviral therapy has resulted in longer life expectancies; however, persons living with HIV are now faced with new morbidities resulting from toxicities and metabolic derangements associated with longV. Stosor (*) Divisions of Infectious Diseases and Organ Transplantation and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611, USA e-mail: [email protected]

term antiretroviral agent exposure or from chronic viral hepatitis. These conditions can lead to end organ disease and, ultimately, death from organ failure. With effective therapies for viral suppression, HIV is no longer considered an absolute contraindication to organ transplantation. Over the past decade, studies of transplantation for HIV+ patients have had encouraging results, such that patients with organ failure are increasingly pursuing transplantation. This review focuses on the current status of organ transplantation for HIV-infected persons, highlighting the outcomes of, the current standards of care for, and unique aspects of posttransplant management of this highly specialized patient population.

Abdominal Organ Transplantation Kidney Transplantation The incidence of end-stage renal disease (ESRD) has increased in the HIV population [2]. An estimated 800 HIVinfected patients develop ESRD annually, and HIV+ patients account for 1 %–2 % of the U.S. dialysis population [3, 4]. HIV-associated nephropathy (HIVAN), hypertension, and diabetes mellitus are leading causes of renal failure [2, 5, 6]. Even though the survival of HIV+ dialysis patients has improved with effective combination antiretroviral therapy (cART), all-cause mortality remains unacceptably high, and survival remains lower for HIV+, as compared with uninfected dialysis patients [2, 7–10]. While cART has reduced the incidence of HIVAN, patients on therapy remain at risk for declining kidney function [7, 11]. In addition to direct drug nephrotoxicity [11–13], cART-related metabolic complications, including diabetes and dyslipidemias, are associated with chronic kidney disease [14]. Additionally,

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hepatitis B (HBV) or C (HCV) virus coinfection increases the risk of kidney failure [11, 15, 16]. It is not unexpected, then, that with this growing burden of advanced kidney disease, HIVinfected persons are seeking renal transplantation. In 2003, a U.S. pilot study demonstrated the feasibility of kidney transplantation in HIV+ individuals, paving the way for active investigation of transplantation for this population [17]. In recent years, single- and multicenter studies throughout the U.S. and Europe have reported results of kidney transplantation for HIV+ patients (see Table 1) [6, 18••, 19–22]. In the largest trial conducted, Stock and colleagues reported the outcomes of 150 HIV-infected patients who were prospectively followed after kidney transplantation. The 1- and 3-year allograft survival estimates were 90.4 % and 73.7 %, respectively, and fell between those reported in the U.S. Scientific Registry of Transplant Recipients (SRTR) for the general (92.5 % and 82.8 %) and older (>65 years of age; 88.3 % and 74.4 %) transplant populations. Additionally, the 1- and 3-year patient survival estimates for HIV-infected kidney recipients were 94.6 % and 88.2 %, respectively, and compared favorably with those reported in the SRTR for general (96.2 % and 90 %) and older (91.8 % and 79.5 %) kidney recipients [18••]. In the U.S. multicenter trial, candidates underwent a careful selection process, and eligibility (Table 2) required receipt of antiretroviral therapy, documented treatment adherence with suppression of HIV, CD4 lymphocyte counts ≥ 200 cells/μL, and control of prior opportunistic infections. These are now accepted criteria for transplant candidacy by centers that treat HIV+ patients [23]. Additionally, both primary and secondary antiinfective prophylaxis for Pneumocystis jeroveci, herpesviruses, Candida spp., Toxoplasma gondii, and Mycobacterium avium complex was utilized. Under these conditions, control of HIV was excellent, and few opportunistic infections or new AIDSdefining conditions were documented. Bacterial infections, however, occurred frequently, especially in recipients who were treated with thymoglobulin or coinfected with HCV [18••]. Although kidney transplant outcomes are favorable, a number of issues complicate the posttransplant course of HIV-infected recipients and may, ultimately, impact outcomes. First, a high incidence of delayed allograft function (DGF), defined as the need for hemodialysis in the immediate posttransplant period, is reported in HIV-infected recipients [18••, 21, 22, 24]. In the U.S. multicenter trial, DGF complicated 15 % of living and 46 % of deceased donor transplants [18••]. Additionally, in a Spanish multicenter study, DGF occurred in 52 % of HIV-infected, as compared with 21 % uninfected, recipients. In this study, HIV, HCV, older recipient age, and increased cold ischemia time predicted DGF [21]. Factors such as use of marginal or extended criteria donor organs or tacrolimus toxicity (see the Pharmacokinetic and Pharmacologic Considerations section

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below) may lead to delayed or poor graft function [6, 24]. The effect of DGF on long-term graft outcomes is not completely clear in this patient population; however, in a multivariate analysis of U.S. multicenter trial data, DGF was not predictive of graft failure [18••]. Perhaps the most intriguing finding of the U.S. multicenter trial, which has been confirmed by others, was the unanticipated high allograft rejection rates of HIV-infected kidney recipients. In the U.S. trial, the 1-year incidence of rejection was 31 %, as compared with 12 % reported to the U.S. SRTR [18••]. Other centers have reported rejection rates ranging from 15 % to 73.9 % [6, 19–21]. Rejection may relate to suboptimal and fluctuating antirejection drug levels caused by drug interactions or to minimization of antirejection therapy out of fear for over-immunosuppression of HIV patients. This leads to the question of what is the optimal immunosuppression regimen for HIV-infected patients, and data are emerging in this area. In the U.S. trial, tacrolimus has emerged as the preferred calcineurin inhibitor for immunosuppression [18••]. IL-2 receptor antagonists such as basiliximab and daclizumab are commonly employed as induction immunosuppression for HIV patients. However, early recognition of the potential for graft rejection prompted use of thymoglobulin, an agent that results in profound and sustained lymphocyte depletion, for induction immunosuppression by some investigators. While many experts believe that induction immunosuppression is necessary to prevent rejection in HIV+ recipients, the safety and efficacy of agents that result in lymphocyte depletion are not well defined in this population. In the U.S. trial, thymoglobulin led to larger and more sustained reductions in CD4 counts and, ultimately, was associated with more severe infections and allograft loss [18••]. In contrast, in a series of 11 HIV+ kidney recipients, 82 % received thymoglobulin induction, all underwent early steroid withdrawal, and the center reported a 9 % 1-year incidence of rejection [25]. In registry studies [26, 27] and in smaller studies[28], it is evident that lymphocyte-depleting induction agents, including thymoglobulin and alemtuzumab, are commonly utilized, but more data are required to determine the effects of induction immunosuppressive agents on infection, allograft, and patient outcomes. The investigators of the U.S. multicenter trial [18••] have proposed alternative explanations for high rejection rates, including allosensitization resulting from incorporation of host human leukocyte antigen molecules into the HIV envelope, nonspecific enhancement of alloimmunity through the homeostatic proliferation of T-cells that occurs with HIV infection, or cross-reactivity of memory T-cell responses resulting from prior infections. This remains an active area of investigation. Although transplantation is a more complicated process in persons with HIV infection, overall good outcomes justify

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Table 1 Outcomes of HIV-infected patients undergoing kidney transplantation Study

N

Immunosuppression regimen Induction (%)

Maintenance (%) CyA (100) SRL (100)

Kumar et al. 2005 [6]a

40

IL2Ra (100)

Stock et al. 2010 [18••]

150

IL2Ra (51) ATG (32)

Touzot et al. 2010 [19]

27

IL2R (96) ATG (4)

Malat et al. 2012 [20]a

92

IL2Ra (100)

Mazuecos et al. 2013 [21]

36

IL2Ra (30) ATG (11)

Steroids (100) FK (66) CyA (22) MMF (87) Steroids CSA FK MMF Steroids CyA (100) SRL (74) MMF or MPA (11) Steroids (100) FK (94) CyA (6) MPA (100) Steroids (100)

Graft rejection rate, %

Graft survival, %

Patient survival, %

1 YR

3 YR

1 YR

3 YR

29

75

–

85

–

33

90

74

95

88

15

100

–

90

–

73.9

–

–

–

–

33.9

91.6

86.2

100

100

N, number of subjects; IL-2Ra interleukin-2 receptor antagonist; CyA cyclosporine A; SRL sirolimus; ATG anti-thymocyte globulin; FK tacrolimus; MMF mycophenolate mofetil; MPA mycophenolic acid a

These studies include data from the same single-center prospective cohort

kidney transplantation for HIV-infected patients with ESRD. Yet European and U.S. investigators have reported low rates of referral of HIV-positive patients for evaluation and listing for transplantation [5, 10, 29]. At one center, only 20 % of

Table 2 Criteria for organ transplantation candidacy in HIV-infected patients [18••, 23] • CD4 + T lymphocyte count ≥ 200 cells/mm3 (≥100 cells/mm3 for liver transplant)a • On stable antiretroviral therapy with undetectable plasma HIV RNA levelb • No wasting syndrome • No active or recent opportunistic infection (OI) • No history of OI for which there is no or limited therapyc • For organ transplantation other than the liver, no evidence of cirrhosis in patients with hepatitis B and/or C coinfection • Meet all other center-specific criteria for transplantation a

If there is a history of opportunistic infection such as Pneumocystis jeroveci pneumonia, then CD4 count ≥ 200 cells/mm3 b

If patient is unable to tolerate HIV therapy due to liver failure, the transplant team may decide to proceed with transplantation if an effective regimen can be initiated posttransplant c

Including progressive multifocal encephalopathy, chronic cryptosporidiosis, primary CNS lymphoma, and visceral Kaposi’s sarcoma

HIV+ candidates were ultimately listed for transplant, as compared with 73 % of uninfected recipients; while barriers to transplant listing included medically valid reasons such as uncontrolled HIV, the predominant barrier was simply failure to obtain medical records documenting CD4 lymphocyte counts and HIV viral load data to determine eligibility [29]. Additionally, there are obstacles to living donor transplantation; most HIV-infected patients consider their HIV status a barrier to living donor transplantation [30]. Even so, analyses of the United States Renal Data System and SRTR indicate the number of kidney transplants performed in HIV+ persons is rising, providing some evidence that, increasingly, these patients have access to transplantation [26, 27]. Liver Transplantation Liver disease, caused by a number of etiologies, has become a significant issue for HIV-positive patients. HBV and HCV are common in the HIV population, with prevalence estimates of 5 %–20 % and 25 %, respectively [31, 32]. Furthermore, HIV infection increases the risk for progressive and advanced liver disease in patients with viral hepatitis [31–33]. Hepatic injury can also result from antiretroviral therapy, whether due to direct hepatotoxicity, hypersensitivity reactions, mitochondrial

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toxicity, steatosis and/or steatohepatitis, or immune reconstitution phenomena [34, 35]. Finally, alcohol and other non-HIV-related causes of liver disease may occur as primary or contributing factors to the development of end-stage liver disease. A number of studies provide evidence that advanced liver disease and its complications are a leading cause of nonAIDS-related morbidity and mortality [34, 36–41]. Primarily due to viral hepatitis coinfection, 14.5 %–50 % of deaths in HIV-infected patients are attributed to liver failure and its complications [34, 37, 38]. In the Swiss HIV Cohort Study, 32 % of deaths in HCV coinfected patients were attributed to liver failure, and active HCV and/or HBV coinfections were associated with a higher risk of death [38]. Accordingly, the need for liver transplantation in this patient population has grown, and there are indications that the number of HIV+ persons undergoing liver transplantation is increasing [42–44]. In a recent analysis of the United Network for Organ Sharing database, the number of liver transplant procedures in HIV+ patients increased steadily during the period spanning 1999–2008; however, only 0.3 % of all transplants were performed in HIV-infected recipients [44]. Selection criteria for HIV+ liver candidates are the same as those for kidney transplantation, with the exception of allowance for (1) CD4≥100 cells/μL because of splenic sequestration in setting of portal hypertension, if there is no opportunistic infection history, and (2) detectable HIV RNA if cART is not tolerated but posttransplant suppression can be predicted [23, 45]. Preliminary and small case series [17, 45–47], a metaanalysis [48], and a registry study [49] have indicated that outcomes of HIV-infected liver recipients vary according to underlying liver disease, and this has become more evident in larger trials (Table 3). For patients with HIV–HBV coinfection, when liver transplantation is performed in the setting of indefinite passive prophylaxis with hepatitis B immunoglobulin and antiviral regimens containing lamivudine and/or tenofovir, excellent outcomes have been reported, with both graft and patient survivals ranging from 85 % to 100 % after 3 to 5 years of follow-up [46, 50]. Control of HIV and HBV infections was excellent, although, in one study, 54 % of liver recipients had intermittent low-level HBV viremia without recurrence of HBV in the allograft [50]. The investigators concluded that due to frequency of breakthrough viremia, lifelong HBV prophylaxis is prudent. The transplant outcomes of patients with HIV–HCV coinfection have not been as favorable. Larger studies indicate significantly lower graft and patient survival rates in HIV– HCV coinfected liver recipients, as compared with HCVmono-infected controls [43, 51–53, 54•, 55•]. In these studies, 1-, 3-, and 5-year graft survival estimates ranged from 52 % to 86 %, 45 % to 60 %, and 31 % to 45 %, respectively; 1-, 3-, and 5-year patient survival estimates ranged from 57 % to

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88 %, 50 % to 62 %, and 33 % to 58 %, respectively. It is clear from some reports that HCV-related complications were more likely to occur in coinfected versus HCV mono-infected patients [51], and HCV recurrences and HCV-related progressive liver disease contributed to poor outcomes [52]. Additionally, severe infections and sepsis, seemingly unrelated to control of HIV, also occurred frequently in these studies and contributed to lower survival [42, 43, 52, 53, 54•]. In the majority of these studies, acute rejection rates exceeded 30 %. In the U.S. multicenter trial, the cumulative incidence of rejection was 39 % in HIV–HCV coinfected recipients at 3 years, as compared with 24 % in HCV-monoinfected controls, and more than half of rejection episodes occurred in the first 3 weeks following transplant. Further analysis demonstrated a protective effect of prednisone and higher tacrolimus levels, suggesting that inadequate immunosuppression may be a factor in the development of allograft rejection. Importantly, though, allograft rejection was a predictor of graft loss in this study [55•]. These disappointing outcomes have prompted further analyses that provide some potentially important insights when proceeding with liver transplantation in HIV–HCV coinfected patients. In the U.S. multicenter trial, independent predictors for liver allograft loss included low body mass index (BMI21 kg/m2, no need for combined liver–kidney transplant, and no HCV+ donor organ should be met when determining candidacy of HIV–HCV coinfected patients for liver transplant [56].

Simultaneous Pancreas–Kidney Transplantation Simultaneous pancreas–kidney transplantation is not commonly performed in type I diabetic patients with HIV infection. In the 10 cases reported in the literature, induction immunosuppression with an IL-2 receptor antagonist and maintenance therapy with prednisone, tacrolimus, and mycophenolate mofetil (or mycophenolic acid) were commonly utilized [57–62]. Recent publications demonstrate good early and intermediate outcomes [59, 60], but most centers document frequent complications such as graft thrombosis, rejection, and bacterial infections, including fatal sepsis [60, 61, 63]. On the basis of these preliminary findings, pancreas transplantation can be successful in HIV-infected patients, but it is prudent to proceed carefully with selection of candidates and posttransplant management to minimize risk of complications.

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Table 3 Outcomes of HIV-infected patients undergoing liver transplantation Study

N

Duclos-Vallee et al. 2007 [52]

35

de Vera et al. 2007 [51]a Coffin et al. 2010 [50]

27 22

DiBenedetto et al. 2011 [53]

23

Anadol et al. 2012 [45]

32

Miró et al. 2012 [42, 54•]

84

Terrault et al. 2012 [55•]

89

Underlying liver disease(s)

HCV (100 %) HCC (9 %) HCV (100 %) HCV (9 %) HBV (100 %) HCC (9 %) HCV (87 %) HBV (26 %) HDV (4 %) HCV (66 %) HBV (38 %) HDV (3 %) HCV (100 %) HBV (15 %) HCC (18 %) HCV (100 %) HBV (6 %) HCC (34 %)

Acute rejection, %

Graft survival, %

Patient survival, %

1 Yr

3 Yr

5 Yr

1 Yr

3 Yr

5 Yr

31

–

–

–

73

–

51

37 23

63 85

52 85

31 –

67 85

56 85

33 –

HCC (57 %) ETOH (9 %)

35

52

45

45

57

50

50

HCC (22 %) ETOH (6 %) Budd-Chiari (3 %)

31

–

–

–

–

–

58 (HCV) 80 (HBV)

38

86

60

45

88

62

54

39

72

53

–

76

60

–

N, number of subjects; HCV hepatitis C virus; HBV hepatitis B virus; HCC hepatocellular carcinoma; HDV hepatitis delta virus; ETOH ethanol a

This study includes 2 liver recipients also reported in the U.S. multicenter trial (Terrault et al.).

Thoracic Organ Transplantation Heart Transplantation and Mechanical Circulatory Support HIV-infected patients are vulnerable to cardiomyopathy resulting from the virus itself, nutritional deficiencies, and drug toxicity [64]. Additionally, in the cART era, cardiovascular disease is a major comorbidity due to the aging HIV population, chronic immune activation, and untoward metabolic effects of antiretroviral therapy [65]. Although advanced heart failure therapies have not been rigorously evaluated for HIV+ patients, reports of successful heart transplantation and mechanical circulatory support are emerging. Since 2001, there are at least 11 reported cases of heart transplantation performed in HIV+ individuals with generally good short-term outcomes, although, interestingly, allograft rejection has complicated the majority of these cases [60, 66–72]. Meeting reports indicate that more heart transplant procedures are performed in the HIV population than the published experience suggests [73]; systematic studies are required to define long-term outcomes and to determine whether complications such as allograft rejection and cardiac allograft vasculopathy will be more problematic for HIV-infected individuals owing to dyslipidemias, immune dysregulation, and chronic immune activation. Limited reports also indicate that HIV-infected patients with heart failure can be supported with ventricular assist devices, whether for temporary support or as a bridge to heart transplantation or destination therapy [72, 74–77]. Problems

such as pump thrombosis and driveline infections [75, 76] have been described, although with so few cases, it is difficult to determine whether such complications will be more prevalent among HIV+ patients, as compared with the general heart failure population. Even with the successes of organ transplantation and preliminary reports of feasibility of advanced heart failure therapies in HIV-infected patients, cardiovascular specialists have been slow to consider HIV+ patients for these therapies [78]. Lung Transplantation In many centers, HIV infection remains an absolute contraindication to lung transplantation. However, some are reconsidering the candidacy of HIV-infected individuals with end-stage lung disease from HIV-associated arterial pulmonary hypertension or other etiology, because of the demonstrated successes with abdominal organ and heart transplantation. There is only one published case of double lung transplantation in an HIV–HBV coinfected man with cystic fibrosis [79], although, almost certainly, other HIVinfected lung recipients exist [80].

Pharmacokinetic and Pharmacologic Considerations The most complex aspect of posttransplant care is the management of concomitant immunosuppressive and

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antiretroviral therapies. The reader is referred to a recent comprehensive review of this topic [81•]. Antiretroviral agents such as the protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), primarily through the inhibition or induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme or inhibition of the intestinal P-glycoprotein (P-gp) transmembrane transporter, can significantly alter the pharmacokinetics of immunosuppressive medications, such as the calcineurin inhibitors (tacrolimus, cyclosporine A) and mTOR inhibitors (sirolimus), resulting in drastic alterations in doses and dosing schedules of these drugs [82, 83]. This lends to the potential for inconsistent and subtherapeutic immunosuppressive levels that may place the patient at risk of rejection or, alternatively, supratherapeutic levels resulting in toxicity [84]. Conversely, NNRTIs have differing potential for induction of CYP3A4, resulting in the need for increased doses of calcineurin and mTOR inhibitors to achieve desired drug levels. The management of drug interactions is further complicated by use of other medications, such as fluconazole, that also inhibit CYP3A4 enzymes. Finally, fluctuating organ function, especially in the early posttransplant period, necessitates frequent dose adjustments of antiretroviral agents such as tenofovir. Transplant specialists have attempted to optimize immunosuppressive therapy in a number of ways. In order to prevent early rejection episodes, some elect to hold antiretroviral therapy in the early days and weeks following transplant until graft function stabilizes and therapeutic levels of calcineurin inhibitors are achieved. Others have reported on calcineurin inhibitor dose finding prior to kidney transplantation [85]. One group reported the use of daily dosing of tacrolimus in very small amounts (0.03–0.08 mg/ d) with stable tacrolimus levels in patients receiving PI-based therapy [86]. Preferences regarding choice of cART posttransplantation are emerging. The integrase inhibitor, raltegravir (RAL), is considered the preferred treatment agent for HIV infection [87]. RAL is not a substrate for CYP3A4 or P-gp, and because of this, interactions with immunosuppression agents is minimal, leading some experts to favor RAL- over PI- and NNRTI-based regimens for HIV+ organ recipients [56, 88, 89]. The CC chemokine receptor (CCR5) is a co-receptor to which HIV-1 binds to gain entry into CD4 lymphocytes. It has long been recognized that persons who are homozogous for a mutant allele, CCR5Δ32 , possess a nonfunctional receptor and are resistant to infection with HIV. However, this nonfunctional receptor is also of interest to transplant specialists due to its apparent role in alloimmunity. Homozygotes for CCR5Δ32 have improved allograft survival and less rejection after transplant [90–93]. Maraviroc is an antiretroviral agent that exerts its effect through CCR5 blockade and, thus, inhibition of HIV-1 entry into CD4 lymphocytes, but in the HIV+ (and general) transplant population, it may have the

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added benefit of reducing susceptibility to rejection [92, 94]. Further study of CCR5 blockade in transplantation is warranted. Sirolimus (rapamycin) is used as an immunosuppressive agent in transplantation, and it is an attractive alternative to calcineurin inhibitors because it lacks the nephrotoxic, diabetogenic, and neurotoxic effects of these drugs. Additionally, sirolimus has antitumor effects [95]. Sirolimus is now known to have anti-HIVeffects through downregulation of CCR5, upregulation of β-chemokines, and blockade of mTOR [96, 97]. There is now limited clinical data supporting the use of sirolimus as an immunosuppressive agent in HIV+ liver recipients [98].

Transplantation Between HIV-Infected Donors and Recipients In South Africa, a resource-limited setting where access to hemodialysis is difficult and HIV-associated nephropathy is prevalent, Muller and colleagues performed four kidney transplants on HIV-infected recipients utilizing known HIVinfected donor organs [99]. This has sparked an international debate regarding the safety and ethics of using HIV-infected organs for transplantation. Currently, the U.S. and many other countries have laws prohibiting the recovery of HIV-infected organs for transplantation (http://www.law.cornell.edu/ uscode/text/42/274.). However, with severe organ shortages for persons on transplant waiting lists, the growing need for organ transplantation in the HIV population, the generally favorable outcomes of organ transplantation for HIVinfected patients, and an estimated 500–600 potential HIVinfected organ donors per year [100••], there is growing support for passage of U.S. legislation that would allow the use of HIV-infected organs for transplantation. Obvious benefits include expansion of the donor pool not only for HIV-infected candidates, but also for all who are waiting for life-saving organs. Safety concerns that will need to be addressed by a careful research agenda, if use of HIVinfected organs is legalized, include suboptimal organ quality due to the high prevalence of kidney and liver disease in the HIV population and potential transmission of HIV that is more virulent or drug resistant or of another infectious agent, such as the hepatitis viruses or occult opportunistic pathogens.

Conclusions Research efforts over the past decade have advanced the care of HIV-infected patients who require organ transplantation. Outcomes are best described for patients who receive kidney or liver transplantation, although data regarding transplantation of pancreas and thoracic organs are emerging. Due to the

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medical complexity of these patients, transplantation of HIV+ persons is best accomplished in centers with an experienced multidisciplinary team that can meet their unique needs. In addition to defining optimal antiretroviral and immunosuppressive therapies, future efforts to improve graft and patient outcomes must address high rejection rates and treatment of HCV coinfected patients. Finally, the use of HIV+ donor organs should be explored as a mechanism for increasing organ availability for HIV+ patients awaiting transplantation. Compliance with Ethics Guidelines Conflict of Interest Valentina Stosor declares no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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