Infections in solid organ transplant HIV-infected patients

12 

Loading....

Loading....

Loading....

Loading....

Loading....

Full text

(1)

Infections in solid organ transplant HIV-infected patients

J. M. Miro1, F. Ag€uero1*, J.-C. Duclos-Vallee2,3,4,5, N. J. Mueller6, P. Grossi7and A. Moreno1on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)

1) Infectious Diseases Service, Hospital Clınic-IDIBAPS, University of Barcelona, Barcelona, Spain, 2) AP-HP H^opital Paul Brousse, Centre Hepato-Biliaire, 3) Inserm, Unite 785, 4) Univ Paris-Sud, UMR-S 785, 5) DHU Hepatinov, 6) Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland and 7) Infectious Diseases Section, Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy

Abstract

Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and Europe indicates that 3- to 5-year survival in HIV/HCV-coinfected liver recipients is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected transplant patients (liver, kidney and heart) was similar to that of non-HIV-infected patients. Preliminary experience with lung transplantation and combined kidney and pancreas transplantation is also satisfactory. Infections in HIV-infected recipients during the post-transplant period are similar to those seen in non-HIV-infected patients, although the incidence rates of tuberculosis and fungal infections seem to be higher. HIV-infected patients who are being evaluated for SOT should follow the same recommendations as those used for non-HIV-infected patients in order to prevent infections during the pre-transplant period. After transplantation, HIV-infected SOT recipients must follow recommendations on post-SOT and anti-HIV immunization and on antimicrobial prophylaxis. The recommended antiretroviral regimen is one based on raltegravir or dolutegravir plus two nucleos(t)ide reverse transcriptase inhibitors (tenofovir+ emtricitabine or abacavir + lamivudine), because it can prevent pharmacokinetic interactions between antiretroviral drugs, immunosuppressive drugs and some of the antimicrobial agents used to treat or prevent post-transplant infections. In this manuscript, we review current recommendations for preventing infections both before and after transplantation. We also analyse the incidence, aetiology and clinical characteristics of opportunistic and non-opportunistic bacterial, mycobacterial, fungal and viral infections in HIV-infected SOT recipients during the post-transplant period.

Keywords: End-stage organ disease, highly active antiretroviral therapy, hepatitis B virus, hepatitis C virus, HIV/AIDS, infections, prophylaxis of opportunistic infections, solid organ transplantation

Article published online: 9 July 2014 Clin Microbiol Infect 2014; 20 (Suppl. 7): 119–130

Corresponding author: J. M. Miro, Infectious Diseases Service, Hospital Clınic. Helios Building, Desk no. 26. Villarroel, 170. Zip Code 08036 Barcelona, Spain.

E-mail: jmmiro@ub.edu

*JMM and FA contributed equally to this work.

Hot Topics

 Infection by human immunodeficiency virus (HIV) is not a contraindication for transplant in appropriate candidates with end-stage organ disease (AII).

 Efforts should be made to identify the HIV serostatus of both the donor and the recipient before solid organ transplant (SOT) in order to prevent transmission of HIV

and to enable appropriate pre-transplant evaluation of patients.

 Most HIV-infected patients with end-stage organ disease who are being evaluated for SOT should follow the general recommendations for non-HIV-infected persons. Liver transplant candidates are an exception, as they can be placed on a waiting list with a CD4+ T-cell count <200/mm3 and must therefore take antimicrobial

(2)

 All patients undergoing SOT must follow recommended preventive measures (e.g. antimicrobial prophylaxis and post-SOT and anti-HIV immunization) in the post-transplant period (BII).

 Although recommendations for prevention of post-trans-plant infections were not specifically thought to be useful in the HIV-infected SOT recipient, they have been validated in several observational studies (BII).

 The combination of two nucleos(t)ide reverse transcriptase inhibitors (tenofovir + emtricitabine or abacavir + lamivu-dine) + raltegravir or dolutegravir seems to be the antiret-roviral regimen of choice in HIV-infected SOT recipients (BII).

 Infections are a major source of morbidity and mortality in the post-transplant period (BII). HIV-related immunosuppression and exogenous immunosuppression due to the immunosup-pressive drugs used for maintenance therapy and to treat rejection play a key role in increased morbidity and mortality.

 Further research is needed in the HIV/AIDS setting to optimize current antimicrobial prophylaxis (i.e. duration of prophylaxis against Pneumocystis jiroveci pneumonia (PCP)) and to evaluate the safety and effectiveness of using HIV-infected donors (e.g. kidney transplantation). It is also important to know the impact of new antiretroviral drugs (e.g. dolutegravir) and new molecules for HCV infection (e.g. protease inhibitors and polymerase inhibitors), both of which are thought to have a safe pharmacokinetic profile and/or optimal clinical effectiveness that could facilitate management of this complex clinical scenario.

Basic research is necessary to improve our knowledge of the cumulative effect of factors, both HIV related and drug related, involved in immunosuppression and the individual role of each factor.

Introduction

With the advent of highly active antiretroviral therapy (HAART) in 1996, patients infected with HIV are living longer and dying from illnesses other than AIDS [1]. Liver disease due to chronic hepatitis C is now a leading cause of mortality among patients coinfected with HIV and hepatitis C virus (HCV) in the developed world [2,3]. The prevalence of end-stage renal disease (ESRD) is also increasing among HIV-infected patients [4], for whom solid organ transplant (SOT) is the only therapeutic option and HIV infection is not a contraindication [5]. Recent experience in North America and Europe indicates that 3- to 5-year survival in HCV/HIV-coin-fected liver recipients is lower than that of HCV-monoinHCV/HIV-coin-fected recipients [6–8]. Conversely, 3- to 5-year survival of non-HCV-coinfected liver recipients and kidney recipients is

similar to that of non-HIV-infected patients [9,10]. Experience with heart [11], pancreas [12] and lung [13] transplantation in HIV-infected patients is very limited. The post-transplant period is complicated by the risk of infection and becomes even more problematic as a result of factors such as pharmacokinetic and pharmacodynamic interactions between drugs (antiretrovirals, immunosuppressors and antimicrobial agents), the increased rate of acute rejection, and HCV re-infection in HIV-infected liver recipients, which is the main cause of mortality. In this context, team learning curves could improve the prognosis of these patients [7].

In the present manuscript, we review infections in HIV-infected SOT recipients, because transplantation in patients with HIV/AIDS has become more common in Western countries in the last decade. Hospitals wishing to carry out transplants in HIV-infected patients must have a multidisciplinary team that can regularly evaluate patients both before and after transplantation. In order to design appropri-ate preventive strappropri-ategies, ensure early diagnosis and select appropriate therapy for potentially life-threatening infections, the team should include staff from the transplant unit itself (medical, surgical, social work and psychological/psychiatric), experts on alcoholism and drug abuse, HIV/infectious disease specialists and tropical medicine specialists.

Magnitude of the Problem in Europe

End-stage liver disease

According to current estimates, there are around 540 000 HIV-infected patients in Western Europe [14]. The preva-lence of coinfection by HCV and HBV in this population is 33% [15] and 9% [16], respectively. Therefore, the estimated number of HCV- and HBV-coinfected patients is around 180 000 and 49 000, respectively [15,16]. In a cross-sec-tional study performed in Spain [17], 8% of coinfected patients had clinical or histological criteria for liver cirrhosis, and 17% met the Spanish criteria for inclusion on an orthotopic liver transplantation (OLT) waiting list. Therefore, there could be approximately 3100 potential candidates for OLT in Europe.

Other end-stage organ diseases

The prevalence of HIV infection in dialysis units varies widely between countries, and even within the same country. Information on prevalence in Europe during the HAART era is scarce. A EuroSIDA survey revealed a prevalence of 0.46% among HIV-infected persons with ESRD in Europe [18].

The prevalence of other end-stage organ diseases in HIV-infected patients in Europe is unknown, although

(3)

end--stage ischaemic cardiovascular disease and, therefore, heart transplantation, is likely to become increasingly prevalent.

Criteria for SOT in HIV-Infected Persons

HIV-infected patients are included on the SOT waiting list according to the specific organ disease, HIV infection criteria and other criteria [3,5].

Organ disease

The disease criteria are the same as for non-HIV-infected transplant patients [3,5].

HIV infection criteria

Most transplant groups from Europe and North America use similar HIV criteria. These are summarized in Table 1 [5,6,19– 22].

 Clinical criteria: Ideally, no patients should have had AIDS-defining diseases, as these increase the risk of reactivation [6]. However, some opportunistic infections (OIs) have been withdrawn as exclusion criteria in most countries, as they can be treated effectively and prevented. In fact, the inclusion criteria for OI were updated in a study sponsored by the National Institutes of Health (NIH)[20], and only untreatable diseases are still exclusion criteria for SOT.

 Immunological criteria: For OLT, most groups [5,6,19–21] agree that the CD4+ lymphocyte count should be >100 cells/mm3. This figure is lower than that recom-mended for other SOT recipients (>200 cells/mm3), because patients with cirrhosis often have lymphopenia due to hypersplenism, which leads to a lower absolute CD4+ count despite high CD4+percentages and good virological control of HIV [5]. On the other hand, in Spain, Italy and the

USA, the CD4+ T-cell count must be >200 cells/mm3 in patients with a previous OI [5, 19, 20]. In the UK [21], the CD4+cut-off is 200 cells/mm3, unless patients have decom-pensated cirrhosis or portal hypertension, which is the same CD4+ cell threshold as used in Spain and the USA (>100 cells/mm3). In France, patients with <100 CD4+ cells/mm3are evaluated on an individual basis.

 Virological criteria: Ideally, the patient should tolerate HAART before transplantation and have an undetectable HIV viral load in plasma using ultra-sensitive techniques (<50 copies/mL) [5,6,21,23]. In some cases (e.g. patients who remain viraemic on HAART), it is essential to carry out antiretroviral sensitivity testing to ascertain real therapeutic options.

HAART regimens should be tailored according to the grade of end-stage organ disease (dose adjustment of ARVs for patients with impaired hepatic function) [24], drug interactions and HIV genotyping results. Some patients do not have an indication for HAART, as they are long-term non-progressors or do not fulfil the immunological or clinical criteria to start treatment and, therefore, have a detectable plasma viral load. In this setting, it is unknown whether and when (before or after transplant) it would be beneficial to initiate HAART so as to reach an undetectable viral load. However, in most centres, HAART is initiated before or after transplantation in order to prevent progression of end-stage organ disease and HIV infection, because the effects of HIV on these organs (e.g. inflammation) contribute to HIV-related morbidity and mor-tality. In addition, HAART-associated sustained viral suppres-sion and higher CD4+ count can delay, prevent or reverse some non-AIDS-defining complications [24].

Other criteria

The candidate must have a favourable psychiatric evaluation [5]. Patients who actively consume drugs or alcohol are

TABLE 1. HIV criteria for SOT in Europe and the USA

Spain [5] Italy [19] UK [21] USA [20] France [6,22]

Previous C events [92]

Opportunistic infections None except PCP, TB, OC

None except PCP, TB, OC

None after HAART-induced immune reconstitution

All except untreatable

diseasesa None except PCP, TB, OC

Malignant neoplasms No No No Not defined

CD4+T-cells/mm3

Liver transplantation >100b >100b >200 or >100 if portal

hypertension >100

b >100c

Other SOT >200 >200 >200 >200 Not defined

Plasma HIV RNA viral load

BDL on HAARTd Yes Yes Yes Yes Yes

SOT, solid organ transplantation; BDL, below detection limit (<50 copies/mL); TB, tuberculosis; PCP, Pneumocystis jiroveci pneumonia; OC, esophageal candidiasis.

aOnly untreatable diseases are exclusion criteria for SOT (e.g. progressive multifocal leukoencephalopathy, chronic cryptosporidiosis, multidrug-resistant systemic fungal

infections, primary CNS lymphoma and visceral Kaposi sarcoma).

bPatients with previous opportunistic infections should have>200 CD4 cells/mm3.

cNo exclusion criteria are available for patients with<100 CD4/mm3; cases should be evaluated on an individual basis. dIf plasma HIV RNA viral load is detectable, post-transplant suppression with HAART should be provided for all liver recipients.

(4)

excluded [5]. A consumption-free period of 2 years is recommended for heroin and cocaine and 6 months for alcohol [5]. Patients who are on stable methadone mainte-nance programmes are not excluded. Finally, patients must show an appropriate degree of social stability to ensure adequate care in the post-transplant period.

Antiretroviral Therapy in SOT Recipients

The optimal HAART regimen in the post-transplant period is currently unknown (Table 2). One of the most challenging treatment issues has been that of managing the numerous drug interactions associated with antiretrovirals, immunosuppres-sive agents and medications such as the anti-HCV direct antiviral agents (DAAs) (Table 3). Some drugs should not be co-administered (i.e. efavirenz and voriconazole at standard doses or rifampin and rilpivirine). In addition, patients receiving regimens based on a ritonavir-boosted protease inhibitor (PI) or cobicistat-boosted elvitegravir require rapid and significant dose adjustments of both calcineurin inhibitors and mTOR inhibitors [6,25–27]. Ritonavir and cobicistat are potent inhibitors of CYP3A4 enzymes [26,27].

Drug interactions also exist with non-nucleoside reverse transcriptase inhibitors (NNRTIs) because of their ability to induce clearance of drugs metabolized by CYP3A4; however,

these drugs seem to be associated with less marked dose adjustments than ritonavir and cobicistat [25]. In any case, levels of immunosuppressive drugs should be closely moni-tored. Interestingly, there is a growing body of knowledge on the appropriateness of HAART regimens, including raltegravir (the first integrase inhibitor) plus two nucleos(t)ide reverse transcriptase inhibitors (NRTI; tenofovir + emtricitabine or abacavir+ lamivudine), which are not a substrate of CYP450 and can therefore be safely used in HIV-1 SOT recipients [24,28–31].

The same pharmacokinetic safety profile is probably obtained with dolutegravir-based HAART, although no pub-lished data are available [32].

Given that raltegravir and, probably, dolutegravir lack significant interactions with calcineurin inhibitors and the new HCV DAAs [28,33,34], management of immunosuppres-sive and HCV treatments is simplified (Table 3). In addition, the results of two clinical studies (liver, kidney and heart recipients treated with raltegravir-based HAART) revealed excellent tolerability without events related to outcome (acute rejection) or to HIV infection [29,31]. Therefore, the combi-nation of two NRTIs (tenofovir/emtricitabine or abacavir/ lamivudine) with a non-boosted integrase inhibitor (raltegravir and, probably, dolutegravir) is the antiretroviral regimen of choice in HIV-infected SOT recipients. The second option could be the combination of two NRTIs plus efavirenz (an NNRTI), because the pharmacokinetic profile of efavirenz is safer than that of ritonavir-boosted PIs.

Finally, given the speed with which new antiretrovirals and DAAs to treat HCV are becoming available, new interactions may emerge; therefore, physicians should consult updated databases on drug interactions [33,35,36].

General

Preventive

Measures

in

the

Pre-transplant Period

Most HIV-infected patients with end-stage organ disease who are being evaluated for SOT do not need to follow a specific antimicrobial prophylactic regimen to prevent OI, because the immunological threshold for waiting list acceptance is a CD4+ T-cell count >200 cells/mm3. The only HIV-infected SOT candidates who can be placed on a waiting list with a CD4+T-cell count of 100–200 cells/mm3are OLT recipients. The 2013 updated guidelines for prevention of OI and primary PCP prophylaxis must be followed (Table 4) [37]. Recurrence of PCP (secondary prophylaxis) must also be prevented [37]. Primary PCP prophylaxis (A1) and secondary PCP prophylaxis (B2) can be stopped in patients with a CD4+ T-cell count>200 cells/mm3for more than 3 months and an

TABLE 2. Recommendations for HAART in HIV-infected

solid organ recipients

1. HAART should be designed on an individual basis, taking into account factors such as grade of end-stage organ disease, drug interactions and, when possible, antiretroviral sensitivity testing 2. The optimal HAART regimen in the post-transplant period is

unknown

3. Pharmacokinetic interactions between antiretrovirals, immunosuppressive agents and other drugs used during the post-transplant period play a major role in this complex clinical s cenario (BII)

4. PIs and cobicistat act as CYP3A4 inhibitors and require rapid and considerable dose adjustment of immunosuppressive agents (BII) 5. NNRTIs (mainly efavirenz and nevirapine) are inducers of CYP3A4

and lead to more rapid elimination of calcineurin inhibitors, thus necessitating higher doses of these drugs (BII)

6. The integrase inhibitor raltegravir is not a substrate of cytochrome P450, thus making it safe and effective in this setting (BII). The second-generation integrase inhibitor dolutegravir could prove to be a useful therapeutic option, although data are lacking

7. The combination of two nucleos(t)ide reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) with a non-boosted integrase inhibitor (raltegravir and, probably, dolutegravir) is the antiretroviral regimen of choice in HIV-infected liver recipients (BII)

(5)

undetectable plasma HIV RNA viral load while on HAART [37]. A previous report showed that discontinuation of primary PCP prophylaxis may be safe in patients with CD4 T-cell counts of 101–200 cells/mm3if the HIV-1 viral load is suppressed [38].

Screening and treatment of latent tuberculosis (TB) infection is a cornerstone of the prevention of OI, owing to the difficulties involved in diagnosis and the impact of the disease on the management of HIV-infected patients (Table 4) [39,40]. SOT candidates with a tuberculin skin test (TST) induration ≥5 mm, a history of untreated tuberculosis or a history of contact with a patient with active tuberculin should be treated with isoniazid (300 mg/day) supplemented with vitamin B6 for 9 months [41]. Ideally, patients should receive this treatment before transplantation, except in the case of OLT, where, if treatment cannot be completed before the procedure, it should be completed after the procedure [40].

Additionally, susceptible HIV-infected patients should receive the vaccines included in the immunization schedules for SOT candidates before transplant (Tables 4 and 5) [33,37,39,42]. In patients with a CD4+ T-cell count <200 cells/mm3

, varicella vaccine and measles, mumps and rubella vaccine are contraindicated [33,37,39,42]. On the other hand, killed and recombinant vaccines (e.g. influenza, diphtheria, tetanus, rabies, HAV, HBV, Japanese encephali-tis and meningococcal) should be administered to HIV-infected persons as they would be to non-HIV-infected persons.

Finally, in order to prevent surgery-related infectious complications, the recommended antimicrobial agents for surgical prophylaxis are the same as for non-HIV-infected patients [43]. Previous case-control studies [44,45] revealed that the rate of surgery-related infections after cardiac [45] and orthopaedic surgery [44] in HIV-infected patients were similar to those reported in non-HIV-infected patients.

General

Preventive

Measures

in

the

Post-transplant Period

HIV-infected patients who undergo SOT are thought to have an increased risk of developing OI resulting from conventional exogenous immunosuppression, which may cause an initial and long-lasting decline in the CD4+ T-cell count, particularly in patients receiving thymoglobulin [9]. Moreover, these patients frequently receive additional doses of immunosuppressive drugs to treat rejection, which is more frequent than in non-HIV-infected patients [7–9,46]. Prophylaxis for prevention of OI is essential and should be administered to HIV-infected transplant recipients (BII) [6,7,37,47] (Tables 4 and 5).

Despite the lack of specific guidelines on prophylaxis regimens for the prevention of OI in HIV-infected transplant recipients, both recommendations on prevention in HIV-in-fected patients [37,48] and general recommendations for SOT recipients [39,40] are being used. These recommendations are summarized briefly in Tables 4 and 5.

TABLE 3. Antiretroviral drug options for patients taking HCV direct-acting antivirals

HCV NS34 PIs HCV NS5A replication

complex inhibitor HCV NS5B polymerase inhibitor Boceprevir 800 mg tid Telaprevir

750 mg tida Simeprevir150 mg qd Faldaprevir240 mg qd Daclatasvir 60 mg qd Sofosbuvir 400 mg qd

HIV PIs

Lopinavir/ritonavir Not recommended Not recommended Not recommended No data No data Recommended

Darunavir/ritonavir Not recommended Not recommended Not recommended Recommended at

120 mg qd

No data Recommended

Atazanavir/ritonavir Consider on an individual basis

Recommended Not recommended Recommended at

120 mg qd

Recommended at 30 mg qd

Recommended HIV NNRTIs

Efavirenz Not recommended Recommended at

1125 mg tid

Not recommended Recommended at 240 mg qd

Recommended at 90 mg qd

Recommended

Rilpivirine Recommended Caution because of

QT prolongation

Recommended No data No data Recommended

Etravirine Consider on an

individual basis

Recommended No data No data No data No data

HIV InSTIs

Dolutegravir Recommended Recommended No data No data No data No data

Raltegravir Recommended Recommended Recommended Recommended No data Recommended

Elvitegravir/cobicistat No data Recommended Not recommended No data No data No data

HIV NtRTI

Tenofovir Recommended Recommended Recommended Recommended Recommended Recommended

CCR5 inhibitor

Maraviroc Reduce maraviroc to

150 mg bid

Reduce maraviroc to 150 mg bid

No data No data No data No data

HIV, human immunodeficiency virus; HCV, hepatitis C virus; PIs, protease inhibitors; NNRTIs, non-nucleoside reverse-transcriptase inhibitors; InSTIs, integrase strand transfer inhibitors; ARV, antiretroviral; tid, three times a day; bid, twice daily; qd, once daily.

Modified from Karageorgopoulos et al. and Antiretroviral Treatment Options for Patients on DAAs - Summary available at http://www.hcvdruginfo.ca (accessed 5 January 2014).

(6)

Post-transplant vaccination has not been fully evaluated in non-HIV-infected patients. However, most centres restart vaccination at approximately 3–6 months after transplantation, once baseline immunosuppression levels are attained [39]. Immunization schedules are indicated in HIV-infected trans-plant recipients, although they must take the CD4+ T-cell count into consideration [37].

The most widely used antimicrobial prophylaxis regimens include antifungal prophylaxis and valganciclovir to prevent cytomegalovirus infection in high-risk recipients [6,49–52]. However, there are differences in the duration of prophylaxis against PCP (life-long in the USA [50], at least 1 year in Spain [53], 6 months in Italy [51] and 3 months in the UK [52]). This issue remains controversial in non-HIV-infected patients [54], and recommendations can vary between transplant centres.

Observational studies [6,49–53,55] have shown that HIV-infected patients do not have a significantly greater risk of OI than non-HIV-infected patients thanks to currently available prophylaxis, monitoring and treatment. The studies cited confirm the appropriateness of these measures (AII).

Prevention of Donor-Transmitted Infections

Pre-transplant screening of infections in organ donors is the same in both HIV-infected and non-HIV-infected patients; HIV-infected donors are ruled out [56]. Of note, in recent years, the use of kidneys from HIV-infected donors for non-HIV-infected kidney recipients with ESRD has been the subject of debate in South Africa [57–60]. The preliminary results for 26 HIV-infected patients who received a kidney from an HIV-infected donor were satisfactory [61]. In 2013, 24 (92%) patients were alive, and most continued to have undetectable HIV viral loads [62]. Moreover, in the USA, the recently passed HIV Organ Policy Equity Act (HOPE) [63] allows transplantation of organs from deceased HIV-infected donors to HIV-infected recipients. This law is expected to expand the number of donor organs available for transplantation in patients living with HIV and to facilitate research into this field. However, we believe that further studies are needed to establish the effectiveness and safety of this type of transplantation [58]. Unfortunately, the results from a similar experience (HIV/HCV-coinfected transplant recipients receiving grafts from an anti-HCV-po-sitive donor) were discouraging, and the procedure is no longer recommended owing to severe and faster HCV recurrence [8].

Post-Transplant Infections in HIV-Infected

SOT Recipients

Nowadays, the vast majority of HIV-infected transplant recipients know their HIV serostatus before transplant. The efforts of transplant professionals and the release of guide-lines for reducing transmission of blood-borne viruses (mainly HIV, HBV and HCV) through organ transplantation have facilitated this knowledge. Conversely, when systematic screening of donors had not yet been fully established, the proportion of transplant patients with HIV seroconversion after transplantation in the pre-HAART era was around 60% (14/25) [64].

Post-transplant infections are a major cause of morbidity and mortality in transplant recipients with HIV infection [53,65,66], and severe infection was generally more frequent in HIV/HCV-coinfected SOT recipients [9,53]. Post-transplant infections can be classified into three types: healthcare-related infections and post-surgical infections (e.g. biliary tract, urinary tract); infections caused by immunosuppressive drug therapy; and infections related to complications of end-stage graft disease (e.g. liver cirrhosis and dialysis).

TABLE 4. Recommendations for prevention of infectious diseases in HIV-infected solid organ transplant (SOT) recip-ients

Pre-transplant period

1. Most HIV-infected SOT candidates must follow the same recommendations as non-HIV-infected candidates (BII) 2. OLT candidates with a CD4 T-cell count between 100 and

200 cells/mm3must take primary PCP prophylaxis (AI) 3. In OLT candidates, primary PCP prophylaxis (AI) and secondary

PCP prophylaxis (BII) should be discontinued for patients who have responded to HAART with an increase in CD4+T-cell counts to >200 cells/mm3for >3 months

4. Live-virus vaccines are not generally recommended in HIV-infected persons (see Table 5) (AIII)

5. Screening for latent tuberculosis should be performed and treatment administered to patients on waiting lists (AII) 6. Recommended antimicrobial agents should be used for surgical

prophylaxis (AII)

Post-transplant period

1. HIV-infected transplant recipients must receive the same prophylaxis for OIs as non-HIV-infected SOT recipients (BII)

2. Antiviral prophylaxis or pre-emptive therapy should be used for the prevention of CMV replication and disease after SOT (BII) 3. Antifungal and PCP prophylaxis should be used (BII), although the

duration of prophylaxis against PCP remains unclear 4. Immunization regimens should be used as in the pre-transplant

(7)

It is generally accepted that the incidence and aetiology of infections in HIV-infected patients during the early post-trans-plant period are similar to those reported in non-HIV-infected patients [67,68]. Moreover, the occurrence of HIV/AIDS-re-lated infections is uncommon when appropriate antimicrobial prophylaxis is administered [6–8,49–51,55]. However, most published results on HIV-infected transplant recipients do not provide details of non-AIDS-related infections after transplan-tation. Furthermore, OI rates are generally not adequately

reported in either HIV-infected cohorts or non-HIV-infected cohorts.

HIV-infected recipients generally receive the same immu-nosuppressive regimens as non-HIV-infected recipients. In order to suppress plasma HIV RNA viral load, HAART is usually administered until the day of surgery and resumed once the patient is stable and oral intake can be reintroduced, as recommended in national guidelines [69,70].

It is difficult to separate the complications of a specific HIV-associated OI from the complications associated with the immunosuppression required for transplantation. Cellular immunity is affected in both cases. In patients on HAART with suppressed viral replication, CD4+ T-cell counts are stable or increased and the frequency of OI decreases [71]. Because all HIV transplant programmes require full control of HIV viral replication and a specific CD4+ T-cell threshold [5,20,21,72,73], it is more likely that OI will be related to a post-transplant immunosuppressive state than to HIV infec-tion. Table 6 summarizes the OIs diagnosed in the major studies on liver and kidney transplantation in HIV-infected patients [9,46,53,74,75].

Infections in HIV-Infected Liver Recipients

The most significant comorbid condition associated with OLT in HIV/HCV-coinfected patients is post-transplant recurrence of HCV infection. In addition, HCV infection is more severe in this group than in non-HIV-infected patients, and fibrosing cholestatic hepatitis is more frequent [7,8,67,76,77]. Con-versely, recurrence of HBV infection is easily prevented in the post-transplant period [10].

TABLE 6. Post-transplant opportunistic infections in HIV-infected liver and kidney recipients

Liver recipients Kidney recipients

Country (reference) Spain [53] France [75] USA [74] Spain [46] USA [9,74]

No. of patients 84 105 125 20 150

Follow-up (months) 24 36 32 40 28

No. of cases with at least one opportunistic infection 9 (11%) 5 (5%) 6 (5%) ND 7 (5%)

Opportunistic infections

Tuberculosis 2 1 0 0 0

PCP 1 0 1 0 1

Oesophageal candidiasis 2 2 3 0 2

Other invasive fungal infections 3a 0 0 1 0

CMV disease 2 1 0 1 0

Other opportunistic infections 0 1b 1c 2d 1e

Neoplasm

Kaposi sarcoma 0 ND 1 0 3

Non-Hodgkin lymphoma 0 ND 0 1 0

ND, no data; PCP, Pneumocystis jiroveci pneumonia; CMV, cytomegalovirus.

aTwo mucormycosis and one aspergillosis. bNon-tuberculous mycobacteria. cBronchial candidiasis. dOther viruses. e

Chronic cryptosporidiosis.

TABLE 5. Guidelines for the vaccination of solid organ transplant candidates and recipients

Vaccine

Before

transplant After transplant

Influenza (I) Yes Yes (every year)

Hepatitis B Yes Yes

Hepatitis A Yes Yes (if HAV-seronegative)

Tetanus Yes Yes (if no booster in the

last 10 years)

Pertussis Yes Yes (especially in patients

who have contact with infants)

Polio (I) Yes Yes

Diphtheria Yes Yes

Streptococcus pneumoniae (P)

Yes Yes (once after 3–5 years)

Varicella (LA) Yesa No

HPV Yes Yes

Rotavirus, measles, mumps, rubella

Yesa(in children or

non-vaccinated adults)

No

Vibrio choleraeb Yes Yes

Yellow feverb Yesa No

Salmonella typhi (I)b Yes Yes

Japanese encephalitisb (JE-MB is an inactivated mouse-brain-derived vaccine)

Yes Yes (this vaccine should

only be given to persons traveling to endemic areas for longer periods of time) I, inactivated vaccine; LA, live-attenuated vaccine; P, polysaccharide vaccine; HPV, human papilloma virus.

aSusceptible patients with CD4 counts≥200 cells/lL. b

Travel vaccine.

(8)

In a Spanish cohort of HIV/HCV-coinfected liver recipients [53], severe infections increased mortality almost two-fold (HR, 2.9). Independently associated factors for severe infection included pre-transplant MELD score >15 (HR, 3.50), non-ta-crolimus-induced immunosuppression (HR, 2.5), and a history of OI prior to transplantation (HR, 2.5). The last of these three groups warrants special attention, because patients are at high risk of dying from severe infection. An AIDS-defining OI before transplantation is not an exclusion criterion if the infection can be prevented or treated [5,20,21,72,73]; however, if this finding is confirmed in larger studies, a pre-transplant AIDS-defining OI could become an exclusion criterion. Effec-tive antiretroviral treatment has been found to have a protective effect [53].

Bacterial infections

In Spain, Moreno et al. [53] evaluated 84 consecutive HIV/ HCV-coinfected liver recipients and found that bacteria were the principal aetiological agent of post-transplant infections. Forty-six per cent of patients developed a bacterial infection during follow-up, and 9.5% had bacteraemia. The incidence of surgical site infection was 2.3% (similar to that observed in non-HIV-infected patients), although the incidence of intra-abdominal infections was slightly higher in HIV-infected recipients (8% vs. 4%) [78]. Most cases of early bacterial infection were related to surgery and invasive procedures. Data from a recent US study [74] reported that 70 of 125 liver recipients (56%) had 243 serious infections, of which 71% were bacterial. The most common sites of infection were the respiratory tract (17%), blood (17%) and the genitourinary tract (12%) [74]. These results are similar to those reported for infections in non-HIV-infected transplant recipients. Nev-ertheless, significantly higher mortality due to infectious complications has been reported in a small case series of HIV-infected recipients (four out of 15) [66].

Opportunistic infections (AIDS-related and non-AIDS-related)

In the study by Moreno et al. [53], approximately 11% of HIV/ HCV-coinfected liver recipients developed an OI (e.g. CMV disease, disseminated herpes simplex virus, invasive fungal infection and tuberculosis). In 44% of cases they were late infections (>6 months post-transplant). In another large Span-ish cohort study [79] of non-HIV-infected SOT recipients, the incidence of OI was only 6%, whereas in that of Moreno et al. the incidence of OI was 40%; at the time of the OI, the CD4+ T-cell count was<200 cells/mm3and plasma HIV-1 RNA viral load was undetectable. This higher proportion is similar to that reported in SOT recipients treated with alemtuzumab (humanized monoclonal anti-CD52 antibody) [80]. Invasive

fungal infections occurred in 7% of patients [53]. The authors report two episodes of zygomycosis (rhinocerebral and surgical site). Another single case of zygomycosis has been published [81].

Ragni et al. [82] found the incidence of invasive fungal infection in the late post-transplant period to be 8% (two of 24 HIV-infected liver recipients). The incidence of invasive fungal infection is slightly higher in HIV-infected transplant recipients and should be prevented [53]. The percentage of patients who developed tuberculosis was 2.4%, and the incidence rate was 3140 cases per 100 000 transplants per year (i.e. four- to five-fold higher than in non-HIV-infected transplant recipients) [53]. The incidence of OI was higher, with a combined HIV-infected sample size of 39 patients (20.5%), than reported in other liver transplant studies [83,84]. Overall, the incidence of post-transplant OI was low when plasma HIV RNA viral replication was controlled and CD4+T-cell count was higher than a specific threshold.

Beatty et al. [74] reported fungal, viral and protozoal infections in 7%, 5% and 1% of cases, respectively; however, culture was negative or not performed in 17% of cases.

Infections in HIV-Infected Kidney Recipients

Bacterial infections

In the largest prospective, non-randomized trial on kidney transplantation (150 HIV-infected patients), Stock et al. [9] reported that 140 infections in 57 cases (38%) required hospital admission. Of these, 69% were bacterial. The three most common sites of infection were the genitourinary tract (26%), respiratory tract (20%) and blood (19%). Sixty per cent of severe infections occurred within the first 6 months after transplantation [9]. Similar results were reported in a French study (27 cases) [85] and a Spanish study (20 cases) [46].

Opportunistic infections (AIDS-related and non-AIDS-related)

A recent international 12-study meta-analysis of 254 patients reported infection in 29% of recipients, although only three were AIDS-defining infections [55].

In the study by Stock et al. [9], no evidence of accelerated HIV disease progression was found, despite an initial decline in the CD4+ T-cell count. HIV replication remained under control on HAART despite challenging interactions between antiretroviral and immunosuppressive drugs. The authors reported two cases of newly diagnosed cutaneous Kaposi sarcoma and one case each of oesophageal candidiasis, presumptive PCP and cryptosporidiosis. The two patients with newly diagnosed Kaposi sarcoma were successfully

(9)

treated with sirolimus, which has been reported to control human herpesvirus-8 infection [86]. A trend toward reduced rates of survival detected among patients with HCV coinfec-tion may be related to an increased risk of other serious infections. Treatment with antithymocyte globulin enabled profound and long-lasting suppression of CD4+T-cell counts, which was associated with an increased risk of infections requiring hospitalization [9,87,88].

Beatty et al. [75] recently reported data on OI in 275 HIV-infected transplant recipients from the USA (150 kidney recipients (from the study by Stock et al. [9]) and 125 liver recipients) [74]. The authors detected only 13 cases of OI: four cutaneous Kaposi sarcoma, two PCP, one cryptosporidiosis and six Candida infections (mostly oesoph-ageal). This low incidence was similar to that previously described [6,89]. Importantly, there were no recurrences of OIs and no differences in survival based upon these infections.

Finally, data from the largest reported cohort of HIV-in-fected kidney recipients reveal that fungal, viral and protozoan infections accounted for 9%, 6% and 1% of OIs, respectively [9]. Polyomavirus (BK virus) nephropathy was reported in five patients [9].

Infections in HIV-Infected Heart, Pancreas

and Lung Recipients

The largest US heart transplantation study [90] describes the medium-term outcome of only five HIV-infected recipients. Postoperative treatment was similar to that of non-HIV-in-fected heart recipients. No surgical wound infection was observed. At least three similar cases have been reported in Europe [11]. Miro et al. [91] reviewed cases of simultaneous pancreas-kidney transplantation in HIV-infected patients. In one case, the pancreas graft failed at 2 weeks, and the patient died at 9 months because of a relapsing multidrug-resistant Pseudomonas aeruginosa infection. A further three patients survived, despite the failure of both the pancreas and kidney grafts in one patient. Grossi et al. [12] recently reported four simultaneous pancreas-kidney transplants in HIV-infected recipients. In this series, the most common infections were urinary tract infection and bacteraemia. Infectious processes occurred in three patients (subdiaphragmatic abscess, pelvic abscess subsequent to complicated cholecystitis, and infected psoas hematoma). The same author [13] reported a case of double lung transplant in an HIV/HBV-coinfected patient with cystic fibrosis and end-stage respiratory failure. The operation was successful, and the patient recovered rapidly after surgery. After 2 years of follow-up, major infectious complications and

rejection have been avoided thanks to careful management of infection and immunosuppression.

Challenges for the Future

 Further data are needed to confirm current findings on SOT in patients with HIV infection. Results from the largest cohorts of HIV-infected transplant recipients will provide more robust evidence in the near future and could help to fill knowledge gaps in this specific clinical setting.

 Further studies should try to identify the risk factors for mycobacterial and fungal infections in HIV-infected SOT recipients in order to prevent these life-threatening diseases.

 Transplantation of organs from deceased HIV-infected donors to HIV-infected recipients is controversial, although it is expected to expand the number of donor organs available for transplantation in HIV-infected patients and will facilitate research in this field. The effectiveness and safety of this approach must be demonstrated, and recommendations should be evidence based.

 Basic research based on the immunological findings under-lying transplantation in the setting of HIV/AIDS should be also a priority area. The optimal immunosuppressive regi-men and the impact of factors affecting immune status (mainly HIV and immunosuppressive drugs) have yet to be elucidated. Research will help us to better manage these patients.

 More work is necessary on specific research lines. It is essential to determine the effect on patient management of new antiretroviral drugs such as dolutegravir and new DAAs for treatment of HCV. These drugs have safer pharmaco-kinetic profiles and, therefore, fewer interactions and are more efficacious. They are expected to facilitate rapid immunosuppression and increase the cure rate in HCV infection. Both factors should simplify the management of HCV and its impact on the development of post-transplant infectious complications and prognosis.

 Finally, we propose that international consensus guidelines for preventing infection in transplant recipients should include a special section on HIV-infected patients.

Acknowledgements

We are grateful for the assistance of Mr R. Rogers, Dr M. Roland and Dr P. Stock for providing the data on OIs in HIV-infected liver and kidney transplant recipients from the US NIH-funded cohort study and to Dr Elina Teicher (France) for her suggestions.

(10)

Funding

This review was supported in part by grants from the Spanish Foundation for AIDS Research and Prevention (FIPSE, Madrid, Spain) (TOH-VIH/05, TOH-VIH/08, TOH-VIH/12 and 24-0858-09) and the Spanish Ministry of Health (Madrid, Spain) (‘Investigacion Clınica Independiente’ grant EC11-150). Dr Fernando Ag€uero held a Rio Hortega Research Grant (CM12/ 00195) from the ‘Instituto de Salud Carlos III’ and the ‘Ministerio de Economia and Competitividad’ Madrid (Spain) in 2013-2015.

Transparency Declaration

The authors declare that they have no conflict of interests.

Reference

1. Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection. Lancet 2010; 376: 49–62.

2. Aguero F, Laguno M, Moreno A, Rimola A, Miro JM. Management of end-stage liver disease in HIV-infected patients. Curr Opin HIV AIDS 2007; 2: 474–481.

3. Miro JM, Aguero F, Laguno M et al. Liver transplantation in HIV/ hepatitis co-infection. J HIV Ther 2007; 12: 24–35.

4. Trullas JC, Cofan F, Tuset M et al. Renal transplantation in HIV-infected patients: 2010 update. Kidney Int 2011; 79: 825–842.

5. Miro JM, Torre-Cisnero J, Moreno A et al. GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain (March, 2005). Enferm Infecc Microbiol Clin 2005; 23: 353–362.

6. Duclos-Vallee JC, Feray C, Sebagh M et al. Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 2008; 47: 407–417. 7. Miro JM, Montejo M, Castells L et al. Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study. Am J Transplant 2012; 12: 1866–1876.

8. Terrault NA, Roland ME, Schiano T et al. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transpl 2012; 18: 716–726.

9. Stock PG, Barin B, Murphy B et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363: 2004–2014. 10. Coffin CS, Stock PG, Dove LM et al. Virologic and clinical outcomes of

hepatitis B virus infection in HIV-HBV coinfected transplant recipients. Am J Transplant 2010; 10: 1268–1275.

11. Castel MA, Perez-Villa F, Miro JM. Heart transplantation in HIV-infected patients: more cases in Europe. J Heart Lung Transplant 2011; 30: 1418. 12. Grossi PA, Righi E, Gasperina DD et al. Report of four simultaneous

pancreas-kidney transplants in HIV-positive recipients with favorable outcomes. Am J Transplant 2012; 12: 1039–1045.

13. Bertani A, Grossi P, Vitulo P et al. Successful lung transplantation in an HIV- and HBV-positive patient with cystic fibrosis. Am J Transplant 2009; 9: 2190–2196.

14. Hamers FF, Downs AM. The changing face of the HIV epidemic in western Europe: what are the implications for public health policies? Lancet 2004; 364: 83–94.

15. Rockstroh JK, Mocroft A, Soriano V et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis 2005; 192: 992–1002.

16. Konopnicki D, Mocroft A, De WS et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS 2005; 19: 593–601.

17. Gonzalez-Garcia JJ, Mahillo B, Hernandez S et al. Prevalences of hepatitis virus coinfection and indications for chronic hepatitis C virus treatment and liver transplantation in Spanish HIV-infected patients. The GESIDA 29/02 and FIPSE 12185/01 Multicenter Study. Enferm Infecc Microbiol Clin 2005; 23: 340–348.

18. Trullas JC, Mocroft A, Cofan F et al. Dialysis and renal transplantation in HIV-infected patients: a European survey. J Acquir Immune Defic Syndr 2010; 55: 582–589.

19. Grossi PA. Update in HIV infection in organ transplantation. Curr Opin Organ Transplant 2012; 17: 586–593.

20. Fox AN, Vagefi PA, Stock PG. Liver transplantation in HIV patients. Semin Liver Dis 2012; 32: 177–185.

21. O’Grady J, Taylor C, Brook G. Guidelines for liver transplantation in patients with HIV infection (2005). HIV Med 2005; 6(suppl 2): 149–153. 22. Duclos-Vallee JC, Tateo M, Teicher E et al. Results of liver transplan-tation in a large cohort of more than 100 HIV infected patients - a monocentric experience. Liver Transpl 2011; 17 (suppl S1): S80. 23. Roland ME, Stock PG. Liver transplantation in HIV-infected recipients.

Semin Liver Dis 2006; 26: 273–284.

24. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/guidelines. (Accessed June 5, 2014). 25. Frassetto L, Floren L, Barin B et al. Changes in clearance, volume and

bioavailability of immunosuppressants when given with HAART in HIV-1 infected liver and kidney transplant recipients. Biopharm Drug Dispos 2013; 34: 442–451.

26. Deeks ED. Cobicistat: a review of its use as a pharmacokinetic enhancer of atazanavir and darunavir in patients with HIV-1 infection. Drugs 2013; 74: 195–206.

27. Perry CM. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (Stribild((R))): a review of its use in the management of HIV-1 infection in adults. Drugs 2014; 74: 75–97. 28. Antonini TM, Furlan V, Teicher E et al. Successful anti-hepatitis C virus

therapy with telaprevir in an HIV/hepatitis C virus co-infected patient with a severe recurrence of hepatitis C virus infection on the liver graft. AIDS 2013; 27: 2655–2657.

29. Miro JM, Manzardo C, Brunet M et al. Combination of Raltegravir Plus Lamivudine or Emtricitabine Plus Abacavir or Tenofovir is Safe, Effective and Prevents Pharmacokinetic Interactions With Immuno-suppressive Drugs in HIV-infected Solid Organ Transplant Recipients. CROI 2011, Boston, Feb 27- Mar 2, 2011. Abstract N-131. 30. Moreno A, Quereda C, Montes M et al. Safe coadministration of

raltegravir-based HAART in HIV-infected patients with HCV-cirrhosis receiving triple therapy with telaprevir or boceprevir. J Acquir Immune Defic Syndr 2012a; 61: e47–e49.

31. Tricot L, Teicher E, Peytavin G et al. Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs. Am J Transplant 2009; 9: 1946–1952.

32. Castellino S, Moss L, Wagner D et al. Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans. Antimicrob Agents Chemother 2013; 57: 3536–3546.

33. Toronto General Hospital’s Hepatitis C Drug Information Web site. Antiretroviral Treatment Options for Patients on DAAs - Summary. Available at: http://www.hcvdruginfo.ca. Accessed (June 5, 2014). 34. Karageorgopoulos DE, El-Sherif O, Bhagani S, Khoo SH. Drug

(11)

antivirals in HIV/hepatitis C virus coinfection. Curr Opin Infect Dis 2014; 27: 36–45.

35. Back D, Gibbons S. The University of Liverpool HIV drug interactions website. http://www.hiv-druginteractions.org/. Accessed (June 5, 2014).

36. Tuset M, Miro JM, Codina C, Ribas J. Guıa de interacciones en HIV. http://www.interaccionesvih.com. Accessed (June 5, 2014).

37. Panel on Opportunistic Infections in HIV-Infected Adults and Adoles-cents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for disease Control and Prevention, the National Institutes of Health, and the HIV Medical Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/ contentfiles/lvguidelines/adult_oi.pdf. Accessed (June 5, 2014). 38. Mocroft A, Reiss P, Kirk O et al. Is it safe to discontinue primary

Pneumocystis jiroveci pneumonia prophylaxis in patients with virolog-ically suppressed HIV infection and a CD4 cell count<200 cells/ microL? Clin Infect Dis 2010; 51: 611–619.

39. Danzinger-Isakov L, Kumar D. Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant 2009; 9(suppl 4): S258–S262.

40. Gavalda J, Vidal E, Lumbreras C. Infection prevention in solid organ transplantation. Enferm Infecc Microbiol Clin 2012; 30(suppl 2): 27–33. 41. Aguado JM, Torre-Cisneros J, Fortun J et al. Tuberculosis in

solid-organ transplant recipients: consensus statement of the group for the study of infection in transplant recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology. Clin Infect Dis 2009; 48: 1276–1284.

42. Rubin LG, Levin MJ, Ljungman P et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2013; 58: 309–318.

43. Bratzler DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70: 195–283.

44. Tornero E, Morata L, Martinez-Pastor JC, Bori G, Mensa J, Soriano A. Prosthetic joint infections due to methicillin-resistant and methicil-lin-susceptible staphylococci treated with open debridement and retention of the prosthesis. Rev Esp Quimioter 2013; 26: 353–359. 45. Jimenez-Exposito MJ, Mestres CA, Claramonte X et al. Mortality and

morbidity in HIV-infected patients undergoing coronary artery bypass surgery: a case control study. Rev Esp Cardiol 2006; 59: 276–279. 46. Mazuecos A, Fernandez A, Andres A et al. HIV infection and renal

transplantation. Nephrol Dial Transplant 2011; 26: 1401–1407. 47. Roland ME, Adey D, Carlson LL, Terrault NA. Kidney and liver

transplantation in HIV-infected patients: case presentations and review. AIDS Patient Care STDS 2003; 17: 501–507.

48. Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009; 58: 1–207.

49. Vernadakis S, Sotiropoulos GC, Brokalaki EI et al. Long-term outcomes of liver transplant patients with human immunodeficiency virus infection and end-stage-liver-disease: single center experience. Eur J Med Res 2011; 16: 342–348.

50. Roland ME, Barin B, Carlson L et al. HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes. Am J Transplant 2008; 8: 355–365.

51. Di Benedetto F, Tarantino G, De Ruvo N et al. University of Modena experience in HIV-positive patients undergoing liver transplantation. Transplant Proc 2011; 43: 1114–1118.

52. Cherian PT, Alrabih W, Douiri A et al. Liver transplantation in human immunodeficiency virus-infected patients: procoagulant,

but is antithrombotic prophylaxis required? Liver Transpl 2012; 18: 82–88.

53. Moreno A, Cervera C, Fortun J et al. Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis c virus-coinfected liver transplant recipients: a FIPSE/GESIDA Prospective Cohort Study. Liver Transpl 2012b; 18: 70–81.

54. Malhotra P, Rai SD, Hirschwerk D. Duration of prophylaxis with trimethoprim-sulfamethoxazole in patients undergoing solid organ transplantation. Infection 2012; 40: 473–475.

55. Landin L, Rodriguez-Perez JC, Garcia-Bello MA et al. Kidney trans-plants in HIV-positive recipients under HAART. A comprehensive review and meta-analysis of 12 series. Nephrol Dial Transplant 2010; 25: 3106–3115.

56. Fischer SA, Avery RK. Screening of donor and recipient prior to solid organ transplantation. Am J Transplant 2009; 9(suppl 4): S7–S18. 57. Muller E, Kahn D, Mendelson M. Renal transplantation between

HIV-positive donors and recipients. N Engl J Med 2010; 362: 2336–2337. 58. Cofan F, Trullas JC, Cervera C et al. Are HIV-infected donors suitable

for renal transplantation? Transplantation 2011; 91: e22–e23. 59. Boyarsky BJ, Hall EC, Singer AL, Montgomery RA, Gebo KA, Segev DL.

Estimating the potential pool of HIV-infected deceased organ donors in the United States. Am J Transplant 2011; 11: 1209–1217.

60. Mgbako O, Glazier A, Blumberg E, Reese PP. Allowing HIV-positive organ donation: ethical, legal and operational considerations. Am J Transplant 2013; 13: 1636–1642.

61. Reardon S. United States to allow transplants of HIV-infected organs. Nature News. Available at http://www.nature.com/news/ united-states-to-allow-transplants-of-hiv-infected-organs-1.14170. Accessed (June 5, 2014).

62. Muller E, Barday Z, Mendelson M, Kahn D. Renal transplantation between HIV-positive donors and recipients justified. S Afr Med J 2012; 102: 497–498.

63. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA 2013; 310: 2492–2493.

64. Tzakis AG, Cooper MH, Dummer JS, Ragni M, Ward JW, Starzl TE. Transplantation in HIV+ patients. Transplantation 1990; 49: 354–358. 65. Baccarani U, Adani GL, Bragantini F et al. Long-term outcomes of

orthotopic liver transplantation in human immunodeficiency virus-in-fected patients and comparison with human immunodeficiency virus-negative cases. Transplant Proc 2011; 43: 1119–1122.

66. Schreibman I, Gaynor JJ, Jayaweera D et al. Outcomes after orthotopic liver transplantation in 15 HIV-infected patients. Transplantation 2007; 84: 697–705.

67. de Vera ME, Dvorchik I, Tom K et al. Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C. Am J Transplant 2006; 6: 2983–2993.

68. Roland ME, Stock PG. Review of solid-organ transplantation in HIV-infected patients. Transplantation 2003; 75: 425–429.

69. Panel of Experts of GESIDA and Spanish Secretariat for the National Plan on AIDS. Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013). Enferm Infecc Microbiol Clin 2013; 31: 604–613.

70. Thompson MA, Aberg JA, Hoy JF et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA 2012; 308: 387–402.

71. Price P, Mathiot N, Krueger R, Stone S, Keane NM, French MA. Immune dysfunction and immune restoration disease in HIV patients given highly active antiretroviral therapy. J Clin Virol 2001; 22: 279–287. 72. Grossi P, Tumietto F, Gabbrielli F, Venettoni S, Rizzato L, Costa A. Liver transplantation in HIV-infected individuals: Results of the Italian National Program. Transpl Int 2005; 18 (S1): 11.

(12)

73. Anonymous. Solid organ transplantation in the HIV-infected patient. Am J Transplant 2004; 4 (suppl 10): 83–88; 1.

74. Beatty S, Barin B, Fox L et al. HIV-related predictors and outcomes in 275 liver and/or kidney transplant recipients. 2011. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, 2011.

75. Teicher E, Duclos-Vallee JC. Opportunistic infections after liver transplantation in patients infected with human immunodeficiency virus. Liver Transpl 2012; 18: 376–377.

76. Duclos-Vallee JC, Falissard B, Samuel D. Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with a synthetic cohort. AIDS 2011b; 25: 1675–1676.

77. Antonini TM, Sebagh M, Roque-Afonso AM et al. Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation. Am J Transplant 2011; 11: 1686– 1695.

78. Asensio A, Ramos A, Cuervas-Mons V et al. Effect of antibiotic prophylaxis on the risk of surgical site infection in orthotopic liver transplant. Liver Transpl 2008; 14: 799–805.

79. Garrido RS, Aguado JM, Diaz-Pedroche C et al. A review of critical periods for opportunistic infection in the new transplantation era. Transplantation 2006; 82: 1457–1462.

80. Peleg AY, Husain S, Kwak EJ et al. Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody. Clin Infect Dis 2007; 44: 204–212. 81. Nichols L, Ocque RZ, Daly I. Zygomycosis associated with HIV

infection and liver transplantation. Patholog Res Int 2011; 2011: 545981. 82. Ragni MV, Belle SH, Im K et al. Survival of human immunodeficiency virus-infected liver transplant recipients. J Infect Dis 2003; 188: 1412– 1420.

83. Di Benedetto F, Di Sandro S, De Ruvo N et al. Human immunode-ficiency virus and liver transplantation: our point of view. Transplant Proc 2008; 40: 1965–1971.

84. Vennarecci G, Ettorre GM, Antonini M, et al. Liver transplantation in HIV-positive patients. Transplant Proc 2007; 39: 1936–1938. 85. Touzot M, Pillebout E, Matignon M et al. Renal transplantation in

HIV-infected patients: the Paris experience. Am J Transplant 2010; 10: 2263–2269.

86. Stallone G, Schena A, Infante B et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med 2005; 352: 1317–1323. 87. Trullas JC, Cofan F, Cocchi S et al. Effect of thymoglobulin induction on

HIV-infected renal transplant recipients: differences between HIV-po-sitive and HIV-negative patients. AIDS Res Hum Retroviruses 2007; 23: 1161–1165.

88. Carter JT, Melcher ML, Carlson LL, Roland ME, Stock PG. Thymo-globulin-associated CD4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant 2006; 6: 753–760.

89. Fung J, Eghtesad B, Patel-Tom K, DeVera M, Chapman H, Ragni M. Liver transplantation in patients with HIV infection. Liver Transpl 2004; 10: S39–S53.

90. Uriel N, Jorde UP, Cotarlan V et al. Heart transplantation in human immunodeficiency virus-positive patients. J Heart Lung Transplant 2009; 28: 667–669.

91. Miro JM, Ricart MJ, Trullas JC et al. Simultaneous pancreas-kidney transplantation in HIV-infected patients: a case report and literature review. Transplant Proc 2010; 42: 3887–3891.

92. Anonymous. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41: 1–19.

Figure

Updating...

References

Updating...

Related subjects :