Renal transplantation in HIV-infected patients: 2010 update

ArticleinKidney International 79(8):825-42 · January 2011with19 Reads
Impact Factor: 8.56 · DOI: 10.1038/ki.2010.545 · Source: PubMed
  • 32.08 · Hospital de Olot and Universitat de Girona, Girona (Spain)
  • 37.78 · University of Barcelona
  • 29.17 · IDIBAPS August Pi i Sunyer Biomedical Research Institute
  • 51.21 · University of Barcelona
Abstract

The prognosis of human immunodeficiency virus (HIV) infection has improved in recent years with the introduction of antiretroviral treatment. While the frequency of AIDS-defining events has decreased as a cause of death, mortality from non-AIDS-related events including end-stage renal diseases has increased. The etiology of chronic kidney disease is multifactorial: immune-mediated glomerulonephritis, HIV-associated nephropathy, thrombotic microangiopathies, and so on. HIV infection is no longer a contraindication to transplantation and is becoming standard therapy in most developed countries. The HIV criteria used to select patients for renal transplantation are similar in Europe and North America. Current criteria state that prior opportunistic infections are not a strict exclusion criterion, but patients must have a CD4+ count above 200 cells/mm(3) and a HIV-1 RNA viral load suppressible with treatment. In recent years, more than 200 renal transplants have been performed in HIV-infected patients worldwide, and mid-term patient and graft survival rates have been similar to that of HIV-negative patients. The main issues in post-transplant period are pharmacokinetic interactions between antiretrovirals and immunosuppressants, a high rate of acute rejection, the management of hepatitis C virus coinfection, and the high cardiovascular risk after transplantation. More studies are needed to determine the most appropriate antiretroviral and immunosuppressive regimens and the long-term outcome of HIV infection and kidney graft.

Full-text

Available from: JC Trullàs, May 01, 2014
Renal transplantation in HIV-infected patients:
2010 update
Joan C. Trullas
1
, Federico Cofan
2
, Montse Tuset
3
, Marı
´
a J. Ricart
2
, Mercedes Brunet
4
, Carlos Cervera
5
,
Christian Manzardo
5
, Marı
´
aLo
´
pez-Dieguez
5
, Federico Oppenheimer
2
, Asuncion Moreno
5
,
Josep M. Campistol
2
and Jose M. Miro
5
1
Internal Medicine Service, Hospital Sant Jaume Olot (Girona), Universitat de Girona, Girona, Spain;
2
Renal Transplant Unit, Hospital
Clinic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain;
3
Pharmacy Department, Hospital Clinic-IDIBAPS, Universitat de Barcelona,
Barcelona, Spain;
4
Toxicology Department, Hospital Clinic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain and
5
Infectious Diseases
Service, Hospital Clinic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain
The prognosis of human immunodeficiency virus (HIV)
infection has improved in recent years with the introduction
of antiretroviral treatment. While the frequency of
AIDS-defining events has decreased as a cause of death,
mortality from non-AIDS-related events including end-stage
renal diseases has increased. The etiology of chronic
kidney disease is multifactorial: immune-mediated
glomerulonephritis, HIV-associated nephropathy, thrombotic
microangiopathies, and so on. HIV infection is no longer a
contraindication to transplantation and is becoming standard
therapy in most developed countries. The HIV criteria used
to select patients for renal transplantation are similar in
Europe and North America. Current criteria state that prior
opportunistic infections are not a strict exclusion criterion,
but patients must have a CD4 þ count above 200 cells/mm
3
and a HIV-1 RNA viral load suppressible with treatment. In
recent years, more than 200 renal transplants have been
performed in HIV-infected patients worldwide, and mid-term
patient and graft survival rates have been similar to that of
HIV-negative patients. The main issues in post-transplant
period are pharmacokinetic interactions between
antiretrovirals and immunosuppressants, a high rate of acute
rejection, the management of hepatitis C virus coinfection,
and the high cardiovascular risk after transplantation. More
studies are needed to determine the most appropriate
antiretroviral and immunosuppressive regimens and the
long-term outcome of HIV infection and kidney graft.
Kidney International (2011) 79, 825–842; doi:10.1038/ki.2010.545;
published online 19 January 2011
KEYWORDS: drug interactions; hepatitis C; HIV infection;
immunosuppression; kidney failure; kidney transplantation
A few years ago, human immunodeficiency virus (HIV)
infection was an absolute contraindication for solid organ
transplantation. Concerns that post-transplant immuno-
suppression could result in accelerated HIV disease and
increased risk for opportunistic infections meant that
HIV-infected patients were not candidates for transp lanta-
tion. Since the introduction of combined antiretroviral
treatment (cART) in 1996, the natural history of
HIV-infected patients has changed dram atically. Although
AIDS-defining events have decreased steadily as a cause of
death, there has been an increase in mortalit y from
non-AIDS-related infections and late-stage organ diseases.
1
The first experiences for solid organ transplantation in
HIV-infected patients were liver transplants in patients with
hepatitis C virus (HCV) coinfection and hepatic cirrhosis.
2
In
the case of end-stage renal disease (ESRD), renal replacement
therapies (hemodialysis and peritoneal dialysis) are an
alternative to renal transplantation. This is one of the reasons
why renal transplantation was not initially considered a
therapeutic option for HIV-infected patients with ESRD.
However, at present, renal transplantation is a valid option in
adequately selected HIV-infected patients with ESRD under
dialysis or pre-emptively before starting dialysis.
3
We present
the state of the art of renal transplantation in HIV-infected
patients, focusing on clinical aspects, therapeutic strategies
(immunosuppressive and antiretroviral treatments), ethical
issues, comorbidity, and challenges that have to be faced in
the coming years.
ETIOLOGY OF KIDNEY DISEASE IN HIV-INFECTED PATIENTS
Nephr opath y is a common finding in patients with HIV
infection and can present as acute or chronic kidney disease.
Acute renal failure can be produced by the toxic effects
of antiretroviral therapy (for example, tenofovir, indinavir)
or nephr oto xic antimicrobial agents used in the treatment of
opportunistic infections (for example, aminogly cosides, ampho-
tericin, foscarnet, trimethoprim-sulfamethoxazole, acyclovir).
4,5
The etiology of kidney disease is multifactorial: immune-
mediated glomerulonephritis, HIV-associated nephropathy
http://www.kidney-international.org review
& 2011 International Society of Nephrology
Received 10 July 2010; revised 23 November 2010; accepted 7
December 2010; published online 19 January 2011
Correspondence: Jose M. Miro, Universitat de Barcelona, Infectious Diseases
Service, Hospital Clinic, Villarroel, 170, 08036 Barcelona, Spain.
E-mail: jmmiro@ub.edu
Kidney International (2011) 79 , 825–842 825
Page 1
(HIVAN), drug-induced renal disease, nonreversible acute
renal failure, or thrombotic microangiopathy. Moreover,
long-term survival and an increase in cART-induced meta-
bolic alterations will possibly cause an increase in diabetes
and hypertensive renal diseases.
5
Classic HIVAN presents histologically as collapsing focal
segmental glomerulosclerosis and clinically as severe protei-
nuria, renal failure, and rapid progression to ESRD. It is the
most common cause of ESRD in untreated HIV-infected
black individuals who develop renal disease. It primarily
occurs in patients of African descent, suggesting a genetic
predisposition to the disease. Risk factors for its development
include a CD4 þ T-cell count o200 cells/mm
3
and a high
HIV-RNA viral load. Characteristic histological findings
include collapsing focal and segmental glomerulosclerosis,
tubular epithelial atrophy with microcystic dilatation of
the tubules, and lymphocytic interstitial infiltration. Viral
infection of renal cells seems to have an important role in
the pathogenesis of HIVAN. Without adequate treatment, the
prognosis of HIVAN is poor. Although there are strong
observational data suppor ting a role for cART in the
treatment of HIVAN, no prospective, randomized, controlled
trials have been performed to support it. In addition,
performance of a randomized trial in this disorder seems
unlikely, as it generally affects indi viduals with uncontrolled
HIV infection who require treatment.
5–7
ESRD AND RENAL REPLACEMENT THERAPY IN
HIV-INFECTED PATIENTS
The global incidence and prevalence of ESRD in HIV-
infected patients is unknown, with only some information
available in selected cohorts of black individuals.
8
Most
studies have focused on chronic kidney disease, although
there is much less information on advanced stages of kidney
disease. A recent EuroSIDA survey revealed a prevalence of
0.46% (95% confidence interval, 0.38–0.54%) among the
HIV-infected population with ESRD in Europe.
9
Prevalence of HIV infection in dialysis units in the United
States, Europe, and other regions
Prevalence of HIV infection in dialysis units varies widely
between countries and even within the same country
(Table 1). In the United States, the number of infected
patients has increased during the past decade. In 2002, 1.5%
(range 0.3–1.5%) and 0.4% (range 0.4–0.8%) of patients were
reported to have HIV infection and AIDS, respectively.
10
In Europe,
11–17
the overall prevalence of HIV infection in
dialysis units was 0–5% in 1980.
11
In the early 1990s, the
European Renal Association-Dialysis and Transplant Associa-
tion created a European registry including 152,658 patients
under dialysis; the prevalence of HIV infection was 0.12%.
12
In the cART era, information on prevalence in European
countries is scarce, with the exception of small isolated
studies from France
14,15
and Spain.
16,17
Other than three small-scale studies from the pre-cART
era, there is little information from other world regions.
18–20
Survival of HIV-infected patients receiving renal
replacement therapy
Survival of HIV-infected patients receiving dialysis has
increased in the last two decades. Early studies from the
1980s reported that survival in patients with newly diagnosed
AIDS and ESRD initiating hemodialysis was poor. Most
of these patients had advanced HIV disease that was often
accompanied by other opportunistic diseases.
21
Outcome
has improved dramatically, and the mortality rate is now
approaching that for ESRD in the general population.
22
A recent study reported survival rates at 1, 3, and 5 years for
HIV-infected patients on dialysis of 95.2, 71.7, and 62.7%,
respectively; these were significantly lower than those of a
matched HIV-negative cohort of dialysis patients.
23
Different
factors have contributed to improved survival, the most
relevant being the introduction of cART and treatment of
opportunistic infections, as well as enhanced dialysis
procedures. Some predictors of survival have been established
in recent studies. The risk factors for mortality in the HIV-
infected dialysis population are a lower CD4 þ T-cell count,
a higher viral load, the absence of cART, and a history of
opportunistic infections.
23–25
In addition, underexposure
or inadequate dose adjustment of cART in patients who
have impaired renal function and/or are receiving dialysis
may contribute to excess mortality among HIV-infected
patients.
26
Despite this overall improvement in survival in
recent years, a study including cohorts comprising black
individuals reported poor survival in the pre-cART and in the
cART era, as a consequence of inadequate HIV treatment
in those patients (nearly half of patients initiating dialysis in
the cART era were not receiving antiretroviral drugs).
8
HIV-INFECTED PATIENTS ON THE RENAL TRANSPLANT
WAITING LIST
Criteria for including HIV-infected patients on the
transplant waiting list
Most transplant groups from Europe and North America
have been working toward harmonizing criteria for solid
Table 1 | Prevalence of HIV infection in dialysis centers in the
United States, Europe, and other regions
Country (reference) Year
Total number
of patients
on dialysis
Prevalence
of HIV
infection (%)
United States
10
1985 ND 0.3
2002 263,820 1.5
Europe
11,12
1984–1986 44000 0–5
1990 152,658 0.12
Italy
13
1990 21,500 0.11
1995 27,000 0.13
France
14,15
1997 22,707 0.36
2002 27,577 0.67
Spain
16,17
2004 4962 1.15
2006 14,876 0.54
Egypt
18
1991 5000 1.64
Japan
19
1986 1314 0
Brazil
20
1986 132 14
Abbreviations: HIV, human immunodeficiency virus; ND, no data available.
826 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 2
organ transplantation in HIV-infected patients.
27–31
These
criteria are summarized in Table 2.
K Clinical criteria: Ideally, no patients should have had
AIDS-defining diseases, as this may lead to a greater risk
for reactivation. However, some opportunistic infections
(tuberculosis, esophageal candidiasis, and Pneumocystis
jiroveci pne umonia) have been withdrawn as exclusion
criteria, because they can be treated effectively and
prevented.
K Immunological criteria: All groups have agreed that the
CD4 þ T-cell count should be 4200 cells/mm
3
for renal
transplantation, because most opportunistic infections
appear when the CD4 þ T-cell count is below this cutoff.
K Virological criteria: The ideal situation is one in which
the patient tolerates cART before transplant with an
undetectable HIV viral load in plasma by ultrasensitive
techniques (o50 copies/ml). In some cases (for example,
patients who remain viremic with antiretroviral medica-
tion), it is essential to carry out antiretroviral sensitivity
testing to ascertain the real therapeutic options.
Some patients do not have an indication for cART, as
they are long-term non-progressors or do not fulfill the
immunological or clinical criteria to start treatment and,
therefore, have viremia that is detectable in plasma.
In this setting, it is unknown whether and when (pre- or
post-transplant) it would be beneficial to initiate cART,
so that an undetectable viral load can be reached.
K Other criteria: The candidate must have a favorable
psychiatric evaluation. Patients who actively consume
drugs or alcohol will be excluded. In Spain, a consump-
tion-free period of 2 years is recommended for heroin
and cocaine and 6 months for other drugs (for example,
alcohol). Patients who are on stable methadone main-
tenance programs are not excluded. Finally, patients must
show an appropriate degree of social stability to ensure
adequate care in the post-transplant period.
Factors associated with failure to include HIV-infected
kidney transplant candidates on the transplant list
There is less information on the evaluation of HIV-infected
patients for transplan tation. The largest study performed
to date retrospectively reviewed 309 potentially eligible
HIV-infected patients who had been evaluated for renal
transplantation. Only 20% were included on the list or
underwent transplant compared with 73% in HIV-negative
patients evaluated during the same period. The most
common factors associated with failure to complete trans-
plant evaluation are: CD4 þ T-cell count and viral load data
not provided at initial evaluation (35%), CD4 þ T-cell count
and viral load not meeting the eligibility criteria (21%), and
other factors including black race (black HIV-infected
patients seem less likely to complete the transplant evalua-
tion, a pattern that has also been observed in the general
transplant population
32
) and a history of illicit drug use.
33
In Europe, recent data from the EuroSIDA cohort study
evaluated this issue among 88 HIV-infected ESRD patients.
Criteria related to poor control of HIV infection (low CD4 þ
T-cell count or detectable viral load) were reported in 30% of
cases and the remaining two-thirds of patients were excluded,
usually because of cardiovascular diseases or diabetes.
9
EXPERIENCE IN RENAL TRANSPLANTATION IN
HIV-INFECTED PATIENTS
Experience in the pre-cART era (before 1996)
Between 1980 and 1990, a total of 39 HIV-infected kidney
recipients (case reports and case series with a small number
of patients) were documented (Table 3).
34–54
After a mean
follow-up of 48 months (range 8–109), 21 patients died
(53.8%). This early experience was discouraging. Most cases
acquired HIV infection by transplantation or by blood
transfusion or through blood products received during or
shortly after transplantation. Transplant recipients with
untreated or unrecognized HIV infection often had rapid
progression of opportunistic infections and poor outcomes.
The development of a screening test for HIV antibodies in
1984 and its mandatory use before blood and organ donation
since 1985 proved crucial in preventing further spread of
the disease by medica l intervention.
34
Swanson et al.
55
performed a retrospective study of a
historical cohort of 63,210 cadaveric kidney recipients
with valid HIV serology entri es in the USRDS (United States
Renal Data System) from 1987 to 1997. At the time of
their procedure, 32 patients (0.05%) were HIV infected. The
5-year patient and graft survival rates were significantly
reduced in HIV-infected recipients (71 and 44%, respec-
tively) in comparison with the USRDS population (78 and
61%, respectively) (Table 4). In the multivariate analysis,
Table 2 | HIV criteria for renal transplantation in Spain, Italy, the United Kingdom, and the United States
Spain
29
Italy
31
United Kingdom
30
United States
a
(ref. 28)
Opportunistic infections Some
b
None in the
previous year
None after cART-induced
immunological
reconstitution
Some
c
Neoplasm No No No
CD4+ T-cell count (cells/mm
3
) 4200 4200 4200 4200
Plasma HIV-1 RNA viral load BDL on cART Yes Yes Yes Yes
Abbreviations: BDL, below detection level; cART, combined antiretroviral treatment; HIV, human immunodeficiency virus.
a
Cooperative Clinical Trials in Adult Transplantation criteria.
b
Previous tuberculosis, Pneumocystis jiroveci pneumonia (PCP), or esophageal candidiasis are not exclusion criteria.
c
PCP and esophageal candidiasis are not exclusion criteria.
Kidney International (2011) 79 , 825–842
827
JC Trullas et al.: Renal transplantation and HIV review
Page 3
HIV-positive status was independently associated with
patient mortality and decreased graft survival.
Experience in the cART era (1996–2010)
In the last few years, retrospective studies, case reports, and
small prospective studies have shown more encouraging
results, suggesting that renal transplantation is feasible in
adequately selected HIV-infected patients. Patient survival
and renal allograft survival are similar to those of non-
HIV-infected patients (Table 5).
9,56–74
One of the lar gest and first experiences in renal
transplantation in HIV-infected patients was reported by
Kumar et al.
65
and included 40 patients. The 1- and 2-year
patient survival rates were 85 and 82%, and graft survival
rates were 75 and 71%, respectively. Plasma HIV-1 RNA
remained undetectable and CD4 þ T-cell counts remained
4400 cells/mm
3
with no evidence of AIDS for up to 2 years.
Acute rejection was frequent (22%).
Roland et al.
66
describe the preliminary results of a
prospective cohort including 18 kidney transplants followed
over 3 years. Patient survival was 94% and graft survival
was 83%. These results were similar to those of the general
transplant population. The CD4 þ T-cell counts and
HIV-RNA levels remained stable. It is important to notice
the high incidence of acute renal rejection at 1 and 3 years (52
and 70%, respectively). In contrast, Gruber et al.
67
recently
reported their experience with 8 HIV-infected renal
transplant recipients; the graft and patient survival rates at
1 year were 88 and 100%, respectively, and the acute rejection
rate was 13%.
The results of the largest prospective, nonrandomized trial
of kidney transplantation in HIV-infected patients have
recently been published. A total of 150 HIV-infected kidney
transplant recipients were followed for up to 3 years at 19 US
transplantation centers. The patient and graft survival rates at
3 years were 88.2 and 73.7%, respectively. These rates were
Table 3 | Renal transplantation in the pre-cART period (before 1996)
a
Author (reference) Year Number Donor Follow-up
b
Fatal outcome
c
Feduska et al.
36
1980 2 Cadaver 44.5 2 (100%)
Kumar et al.
37
1982 1 LD 8 1 (100%)
Imbasciati et al.
38
1982 1 Cadaver 50 1 (100%)
Milgrom et al.
39
1982 1 Cadaver 19 1 (100%)
Lang et al.
40
1983 1 Cadaver 17 0
Poli et al.
41
1983–1985 8 Cadaver 51 3 (37.5%)
Erice et al.
42
1983–1984 2 Cadaver 74.5 0
Prompt et al.
43
1984 2 Cadaver 26.5 2 (100%)
L’age-Stehr et al.
44
1984 1 Cadaver 74 1 (100%)
Schwartz et al.
45
1983–1984 4 Cadaver 69.2 2 (50%)
Margreiter et al.
46
1984 1 Cadaver 69 0
Briner et al.
47
1984 1 Cadaver 48 1 (100%)
Ahuja et al.
48
1984 1 Cadaver 109 1 (100%)
Simonds et al.
49
1985 2 Cadaver 23 2 (100%)
Bowen et al.
50
1986 1 Cadaver 31 0
Ward et al .
51
1986 1 Cadaver 31 0
Kerman et al.
52
1987 2 Cadaver 27.5 1 (50%)
Carbone et al.
53
1988 2 1 Cadaver/1 LD 31.5 2 (100%)
Tzakis et al .
54
1981–1990 5 Cadaver 33 1 (20%)
Global 1980–1990 39 37 Cadaver/2 LD 48 (8–109) 21 (53.8%)
Abbreviations: cART, combined antiretroviral treatment; LD, living donor.
a
Adapted from Schwarz et al.
34
and Trullas et al.
35
b
Mean time in months.
c
Number (percentage).
Table 4 | Patient and graft survival rates in HIV-positive renal transplant recipients. Differences between pre-cART and cART
era
Pre-cART era, 1987–1997
a
cART era, 2003–2009
b
5-year survival rates 1/3-year survival rates
USRDS ( n=63,210) HIV + (n=32) P-value SRTR (age X65)
c
SRTR (overall)
c
HIV + (n=150) P-value
Patient survival 78% 71% o0.05 91.8/79.5% 96.2/90.6% 94.6/88.2% NS
Graft survival 61% 44% o0.05 88.3/74.4% 92.5/82.8% 90.4/73.7% NS
Acute rejection 48.4% 50% 12.3%
d
31/41%
Abbreviations: cART, combined antiretroviral treatment; HIV, human immunodeficiency virus; NS, non significant; SRTR, US Scientific Registry of Transplant Recipients;
USRDS, United States Renal Data System.
a
Swanson et al.
55
b
Stock et al.
74
c
SRTR survival estimates for older kidney transplant recipients (age X65 years) and for all kidney transplant recipients.
d
SRTR 1-year acute rejection rate (SRTR 3-year acute rejection rate not available).
828 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 4
generally between the reported rates in the national database
for older kidney-transplant recipients (X65 years of age) and
for all kidney-transplant recipients (Table 4).
74
European experience
In Europe, experience on renal transplantation is scarce. The
first report was from Toso et al.,
61
who described a combined
kidney–pancreas transplant in an HIV-infected recipient in
Switzerland. This experience was later extended by Mu
¨
ller
et al.,
68
with two kidney and five liver transplants. Ballarin
et al.
69
reported the first case of combined kidney–liver
transplant in an HCV/HIV-coinfected patient with hemo-
philia A. However, the first series of renal transplantation in a
European country included 10 transplants performed in
Spain between 2001 and 2004.
64
The same authors recently
updated these results comparing the outcome of 20 HIV-
infected kidney recipients with 40 matched HIV-negative
patients and found similar patient survival but worse graft
survival in the HIV-infected group.
71
We reported our experience with three HIV-infected
kidney recipients who received thymoglobulin as induction
therapy. Profound lymphocytopenia was observed in the
post-transplant period, but this was not associated with
an increased risk of bacterial or opportunistic infections in
comparison with a control cohort of 23 HIV-negative kidney
recipients.
70
Trullas et al.
9
reported their experience with 26
HIV-infected patients from the EuroSIDA cohort study who
received a renal transplant between 2000 and 2004; the
survival rate was 100%. Finally, two recent publications have
reported the experience with 34 renal transplants performed
in France.
72,73
Acute rejection rate in the cART era
Most studies report a high rate of acute rejection in
comparison with the low rate of acute rejection in non-
HIV-infected renal transplant recipients. There is high
variability between studies, but in some series the rate is
450%. The explanation remains unclear, although immu-
nological, pharmacological, and racial factors seem to have a
role; in any case, it does not seem to affect allograft survival
rates. In the National Institutes of Health trial, the only
variables associated with an increased risk of graft rejection
were the use of a kidney from a deceased donor and the use
of cyclosporine.
74
Drug interactions resulting in altered
exposure to immunosuppressants may be associated with
rejection. The use of new antiretrovirals (for example,
raltegravir) with no interactions with calcineur in inhibitors
may contribute to more stable immunosuppressive regimens,
and therefore a lower risk of acute kidney rejection.
75
On the other hand, experimental and clinical research
implicates cytokines and chemokines in the process of
transplant rejection. Patients who were homozygous for CC
chemokine receptor 5 (CCR5) with a 32-bp deletion
(CCR5D32) show longer survival than those with other
genotypes. Antiretroviral drugs with new mechanisms
of action, such as the CCR5 inhibitor maraviroc, could have
an important role in avoiding acute rejection in HIV-infected
renal transplant recipients.
76,77
Table 5 | Renal transplantation in the cART period (1997–2010)
Author (reference) Year N Donor Follow-up
a
Acute rejection
b
Graft survival Patient survival
Abbott et al.
56
1996–2001 47 Cadaver 31 ND 98% 96%
Qiu et al.
57
1997–2004 38 ND 60 0 76% 91%
Kuo et al.
58
1999–2000 2 ND 6 ND ND 100%
Stock et al.
59
2000 6 4 Cadaver/2 LD 10 4 100% 100%
Roland et al.
60
2002 26 ND 10 10 (38) 88% 92%
Toso et al.
61
2000 1
c
Cadaver 84 0 100% 100%
Kumar et al.
62
2002 12 ND 12 4 (33) 100% 100%
Stock et al.
63
2003 10 6 Cadaver/4 LD 16 5 (50) 100% 100%
Mazuecos et al.
64
2001–2005 10 Cadaver 16 4 (40) 90% 100%
Kumar et al.
65
2001–2004 40 36 Cadaver/4 LD 24 9 (22) 71% 82%
Roland et al.
66
2000–2003 18 10 Cadaver/8 LD 36 12 (70) 83% 94%
Gruber et al.
67
2004–2007 8 7 Cadaver/1 LD 15 1 88% 100%
Muller et al.
68
ND 2 Cadaver 13 1 100% 100%
Ballarin et al.
69
2007 1
d
1 Cadaver 12 0 100% 100%
Trullas et al.
70
2005–2006 3 3 Cadaver 24 2 100% 100%
Mazuecos
71
2001–2009 20 ND 38 8 (40) 74% 95%
Trullas et al.
9
2000–2004 26
e
21 Cadaver/1 LD ND 8 (30) 77% 100%
Billault et al.
72
ND 7 Cadaver 12 0 100% 100%
Touzot et al.
73
2005–2009 27 25 Cadaver/2 LD 29 4 (15%) 96% 98%
Stock et al.
74
2003–2009 150 102 Cadaver/48 LD 20.4 41%
f
73.7%
g
88.2%
g
Abbreviations: cART, combined antiretroviral treatment; LD, living donor; ND, no data available.
a
Mean time in months.
b
Number (percentage when NX4).
c
Pancreas–kidney transplant.
d
Kidney–liver transplant.
e
Data available for 22 patients.
f
Cumulative incidence of rejection at 3 years (49 (33%) patients had 67 acute rejection episodes).
g
Three-year survival rates.
Kidney International (2011) 79 , 825–842
829
JC Trullas et al.: Renal transplantation and HIV review
Page 5
SPECIAL CONSIDERATIONS FOR RENAL TRANSPLANTATION
IN HIV-INFECTED PATIENTS
Renal transplantation in HIV-infected patients is a complex
scenario requiring a multidisciplinary approach. Teams
should include nephrologists, urologists, infectious diseases
and HIV specialists, psychologist/psychiatrists, experts on
alcoholism and drug abuse, and social workers. Several issues
should be taken into account when treating HIV-infected
renal transplant recipients.
Antiretroviral therapy in ESRD
In patients with ESRD, appropriate dose reduction is
warranted for antiretrovirals that are eliminated mainly via
the kidney, with additional doses given after hemodi alysis
for those drugs that are readily removed by dialysis. There is
little clinical evidence on the dosage of antiretrovirals in
ESRD patients,
78–93
but some general recommendations have
been made. A summary of these recommendations is
provided in Table 6. As nucleoside and nucleotide reverse
transcriptase inhibitors (NRTIs) are eliminated mainly by the
kidneys, a reduced dosage is required in patients with
impaired renal function. Over- or under-prescription of these
drugs could lead to toxicity or virological failure, respectively.
Furthermore, because NRTIs are easily removed by dialysis,
they should be administered after dialysis. The exception is
abacavir, which has low urinary excretion, and, therefore, no
requirement for dose adjustment. However, abacavir has
been associated with increased cardiovascular risk, and must
be prescribed with caution in pati ents with previous
cardiovascular events.
79,81
Abacavir should only be adminis-
tered in patients who are HL A-B*5701 negative. On the other
hand, non-nucleoside reverse transcriptase inhibitors
(NNRTIs), protease inhibitors, and fusion inhibitors are
generally metabolized by the liver and excreted into the
urine in low amounts. Doses of NNRTIs, protease inhibitors,
enfuvirtide, and raltegravir do not need to be adjusted in
patients with chronic kidney disease.
78–81
For nevirapine, an
additional 200 mg dose is indicated following each
dialysis session. Atazanavir boosted with ritonavir should
be applied in patients under dialysis because of the lower
atazanavir concentrations observed in those patients. Dose
adjustment for maraviroc depends on coadministered
drugs.
78–93
Based on the information presented above, the ideal cART
for ART-naive patients undergoing dialysis is a regimen
containing abacavir (if the patient has no history of
cardiovascular risk and a plasma RNA v iral load of
o100,000 copies/ml)
81
or tenofovir and lamivudine/emtrici-
tabine combined with a third drug that can be efavirenz, a
ritonavir-boosted protease inhibitor, or raltegravir. In
patients with effective cART and NRTI side effects, the cART
regimen could be simplified to monotherapy with lopinavir/
ritonavir or darunavir/ritonavir
94–96
or a ritonavir-boosted
protease inhibitor with raltegravir. In patients with v irologi-
cal failure, rescue treatment should be based on a genotypic
resistance stud y. When the patient is close to the renal
transplant, and in order to avoid pharmacokinetic drug
interactions with immunosuppressive drugs and renal
toxicity in the graft, we would recommend, if there are no
contraindications, abacavir, lamivudine, and raltegravir as
first choice or efavirenz as an alternative.
Donor issues
In the pre-cART era, all transplant organs for HIV-infected
patients were from cadaveric donors. In recent years, the
number of living donors has increased, and there is no
contraindication for the use of living donors in HIV-infected
patients. The largest experience with 48 liv ing donors has
recently been reported, finding that the use of a graft from a
living donor was protective for graft loss.
74
Organ transplan-
tation from HIV-infected kidney donors is contraindicated at
present, but its potential utility has recently been consid-
ered.
97
In South Africa, the first organ transplants involving
four HIV-infected recipients who received kidneys from
deceased HIV-infected donors were performed in 2008.
98
At
12 months after transplantation, the four recipients had good
renal function, did not have significant graft rejection, and
HIV infection remained well controlled under cART. Organ
transplantation between HIV-infected patients is controver-
sial, because in addition to ethical issues, recipients can
acquire a different and more aggressive HIV strain (for
example, a different clade or recombinant virus or a virus
with a X4 tropism) from the donor, including HIV drug-
resistant strains, leading to superinfection and HIV disease
progression, can acquire other viruses or subclinical infec-
tions and, finally, the graft quality from the HIV donor may
not be optimal because of undetected factors at the time of
screening and donation. In our opinion, these transplants
should not be performed in the Western World in clinical
practice until their efficacy and safety is evaluated in
prospective long-term controlled studies. In countries with
a resource-limited health system, where there is a high
prevalence of HIV in the general population and HIV
infection is an absolute exclusion criteri on for access to
dialysis or renal transplantation, the use of HIV-infected
donors would increase the donor pool, thus providing renal
allografts to patients who would otherwise die as a
consequence of ESRD. In these cases, the balance between
justice and equity is more difficult. Such issues should
encourage intense scientific debate, given their ethical,
nephrological, virological, and clinical implications.
99
Antiretroviral therapy in renal transplant recipients
The ideal antiretroviral regimen has not been established for
HIV-infected kidney transplant recipients, and general
recommendations for treating HIV-infected patients must
be followed.
79–81
However, it is evident that the ideal
therapeutic regimen must be powerful and sustainable and
aim to achieve and maintain continuous viral suppression
and an increased CD4 lymphocyte count. In addition, in
order to preserve renal graft function, while avoiding the
pharmacokinetic interactions with immunosuppressive drugs
830 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 6
Table 6 | Antiretroviral dosing recommendations in patients with renal impairment
a
Antiretroviral Renal insufficiency HD/CAPD
NRTIs
Abacavir No dosing adjustment is needed No dosing adjustment is needed.
HD: minimally eliminated. Could be dosed independently of HD
session
Didanosine
(enteric-coated)
X60 kg
CrCl X60: 400 mg every 24 h
CrCl 30–59: 200 mg every 24 h
CrClo30: 125 mg every 24 h
HD/CAPD: 125 mg every 24 h. It is not necessary to administer a
supplemental dose after HD
o60 kg
CrCl X60: 250 mg every 24 h
CrCl 10–59: 125 mg every 24 h
CrCl o10: Not suitable for use in patients o60 kg
with CrCl o10 ml/min. An alternate formulation of
didanosine should be used (Videx pediatric powder
for oral solution 75 mg every 24 h)
HD/CAPD: An alternate formulation of didanosine should be
used (Videx pediatric powder for oral solution 75 mg every 24 h)
Emtricitabine Capsules
CrCl X50: 200 mg every 24 h
CrCl 30–49: 200 mg every 48 h
CrCl 15–29: 200 mg every 72 h
CrClo15: 200 mg every 96 h
Oral solution 10 mg/ml. Due to a difference in the
bioavailability of emtricitabine between the hard
capsule and oral solution presentations, 240 mg
emtricitabine administered as the oral solution (24 ml)
should provide similar plasma levels to those
observed after administration of one 200 mg
emtricitabine hard capsule).
CrCl X50: 240 mg (24 ml) every 24 h
CrCl 30–49: 120 (12 ml) mg every 24 h
CrCl 15–29: 80 mg (8 ml) every 24 h
CrClo15: 60 mg (6 ml) every 24 h
Capsules
HD: 200 mg every 96 h, after HD
CAPD: ND
Oral solution (10 mg/ml)
HD: 60 mg (6 ml) every 24 h, after HD
CAPD: ND
Lamivudine
b
CrCl X50: 150 mg every 12 h or 300 mg every 24 h
CrCl 30–49: 150 mg every 24 h
CrCl 15–29: 100 mg every 24 h (first dose 150 mg)
CrCl 5–14: 50 mg every 24 h (first dose 150 mg)
CrCl o5: 25 mg every 24 h (first dose 50 mg)
HD: 25 mg every 24 h (first dose 50 mg), after HD
Stavudine X60 kg
CrCl X50: 40 mg every 12 h
CrCl 26–49: 20 mg every 12 h
CrCl 10–25: 20 mg every 24 h
CrCl o10: 20 mg every 24 h
HD: 20 mg every 24 h, after HD
o60 kg
CrCl X50: 30 mg every 12 h
CrCl 26–49: 15 mg every 12 h
CrCl 10–25: 15 mg every 24 h
CrCl o10: 15 mg every 24 h
HD: 15 mg every 24 h, after HD
Zidovudine Significantly elevated GZDV (the major metabolite of
zidovudine) plasma concentrations
CrCl 10–50: 250–300 mg every 12 h
CrCl o10: 250–300 mg every 24 h
300 mg every 24 h, after HD
HD and CAPD appeared to have a negligible effect on the
removal of zidovudine, whereas GZDV elimination was
enhanced.
NtA
Tenofovir
disoproxil fumarate
CrCl X50: usual dose
CrCl 30–49: 300 mg every 48 h
CrCl 10–29: 300 mg every 72–96 h (dosing twice a
week)
No dosing recommendations can be given for non-
HD patients with creatinine clearanceo10 ml/min
HD: 300 mg tenofovir disoproxil (as fumarate) may be
administered every 7 days following completion of a HD session
(assuming three HD sessions per week, each of B4 h duration or
after 12 h cumulative HD)
NNRTI
Efavirenz Usual dose HD: limited data suggest that there is no reason to adjust the
dose
CAPD: pharmacokinetic data of only one patient suggest that
there is no reason to adjust the dose
Nevirapine CrCl X20 ml/min. Usual dose HD: an additional 200 mg dose of nevirapine following each
dialysis treatment is recommended
Table 6 continued on following page
Kidney International (2011) 79 , 825–842 831
JC Trullas et al.: Renal transplantation and HIV review
Page 7
Table 6 | Continued
Antiretroviral Renal insufficiency HD/CAPD
Etravirine (TMC-125) Usual dose HD/CAPD: as etravirine is highly bound to plasma proteins,
it is unlikely that it will be significantly removed by HD or PD
PI
Amprenavir Usual dose
Because of the potential risk of toxicity from the large
amount of the excipient propylene glycol, Agenerase
oral solution is contraindicated in patients with renal
failure.
HD/CAPD: as amprenavir is highly bound to plasma proteins,
it is unlikely that it will be significantly removed by HD or PD
Atazanavir Usual dose HD/CAPD: as atazanavir is highly bound to plasma proteins, it is
unlikely that it will be significantly removed by HD or PD
HD: consider using atazanavir boosted with ritonavir. Although
ATV was negligibly eliminated by HD (2%), subjects on HD had
substantially lower ATV levels than controls (AUC 42% lower on
HD days, 28% lower on non-HD days). The mechanism for this
effect is not known (limited data). TDM is advised
Darunavir Usual dose HD/CAPD: as darunavir is highly bound to plasma proteins, it is
unlikely that it will be significantly removed by HD or PD
Fosamprenavir Usual dose HD/CAPD: as amprenavir is highly bound to plasma proteins,
it is unlikely that it will be significantly removed by HD or PD
Indinavir Usual dose HD: limited data showed minimal elimination of indinavir during
a dialysis session
Lopinavir/r Usual dose HD: usual dose. In 13 patients who were on HD LPV AUC values
were similar to those obtained in patients with normal renal
function
CAPD: ND. As lopinavir and ritonavir are highly bound to plasma
proteins, it is unlikely that it will be significantly removed by
CAPD.
Nelfinavir Usual dose HD: it is unlikely that it will be significantly removed by HD.
Data from one patient showed no removal of nelfinavir by a 4 h
HD session
CAPD: it is unlikely that it will be significantly removed by PD.
Data from one patient showed dialysate nelfinavir
concentrations below the limit of detection
Ritonavir Usual dose HD/CAPD: as ritonavir is highly bound to plasma proteins,
it is unlikely that it will be significantly removed by HD or PD
Saquinavir Usual dose HD/CAPD: as saquinavir is highly bound to plasma proteins,
it is unlikely that it will be significantly removed by HD or PD
Tipranavir Usual dose HD/CAPD: as tipranavir is highly bound to plasma proteins,
it is unlikely that it will be significantly removed by HD or PD
Fusion inhibitors
Enfuvirtide (T-20) No dosing adjustment is needed HD: usual dose (limited data)
CCR5 co-receptor
antagonists
Maraviroc (UK-427857) No dosing adjustment is needed without potent
CYP3A4 inhibitors or inducers
Postural hypotension may increase the risk for
cardiovascular adverse events in patients receiving
maraviroc who have severe renal impairment or ESRD
(creatinine clearance o30 ml/min). Maraviroc should
not be prescribed for patients with severe renal
impairment who are receiving CYP3A inhibitors or
inducer
HD/CAPD: ND
Integrase inhibitors
Raltegravir (MK-0518) No dosing adjustment is needed ND
Abbreviations: ATV, atazanavir; AUC, area under the plasma concentration time curve; CAPD, continuous ambulatory peritoneal dialysis; CrCl, creatinine clearance;
ESRD, end-stage renal disease; HBV, hepatitis B virus; HCV, hepatitis C virus; HD, hemodialysis; HIV, human immunodeficiency virus; LPV, lopinavir; ND, no data available;
NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NtA, nucleotide reverse transcriptase inhibitor; PD, peritoneal dialysis;
PI, protease inhibitor; TDM, therapeutic drug monitoring.
a
Adapted from Spanish GESIDA/National AIDS Plan Recommendations for antiretroviral therapy in HIV-infected adults, January 2008.
79
b
Dose adjustment for HIV-1 and not for HBV.
832 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 8
and their side effects, the antiretrovirals included in the
regimen should have these two additional properties:
1. Low probability of inducing dyslipidemia, osteopenia/osteo-
porosis, insulin resistance, and r enal toxicity (all of which are
side effects of immunosuppressive drugs). Cardiovascular
safety should also be taken into consideration.
2. Avoidance of pharmacokinetic interactions with calcineurin
inhibitors (cyclosporine and tacrolimus) and mammalian
target of rapamycin (m-T OR) inhibitors (sirolimus) that are
metabolized by cytochrome P450.
If there are no contraindications, we recommend abacavir
(or tenofovir as an alternative) and lamivudine/emtricitabine
combined with ralt egravir as the first-choice regimen or
efavirenz as an alternative. Recommendations on antiretro-
viral drug combinations in renal transplant recipients
are summarized in Table 7. Finally, frequent viral load
monitoring in the early period after transplantation is
highly recommended, and resistance testing must also be
considered.
Immunosuppression
The antiviral effects of immunosuppressive drugs have been
extensively reviewed elsewhere and are beyond the scope of this
review.
100
Howev er, some brief recommendations can be made:
1. Calcineurin inhibitors: There are no studies comparing
the effects of cyclosporine and tacrolimus on the course of
HIV infection. Cyclosporine is been the most frequently
used drug, in the published experience, probably because
of evidence demonstrating its antiretroviral and/or
immunomodulating effects.
101
However, the rate of acute
rejection is hig her with cyclosporine than with tacroli-
mus.
74
In this setting, some centers use tacrolimus as
the ‘first-line’ calcineurin inhibitor.
2. Mycop henolate mofetil: this drug has inhibitory effects on
HIV replication and is synergistic with some NRTIs.
102–104
The leukocyte count should be monitored regularly
because of the myelosuppressive effect of the drug .
3. m-TOR inhibitors: Sirolimus does not seem to have a
negative effect on HIV-infected patients, although experi-
ence with this drug remains scarce. In experimental
studies, sirolimus reduces CCR5 levels in CD4 þ T cells,
inhibits R5 HIV-1 replication, and increases the antiviral
activity of fusion inhibitors and CCR5 antago nists.
105
In addition, its antiproliferative effect can prove useful
in patients with solid organ transplantation-associated
Kaposi sarcoma.
106
Leukocyte count monitoring is also
recommended.
4. Basiliximab/daclizumab: These monoclonal anti-interleu-
kin-2 receptor antibodies have been shown to increase
CD4 T-cell counts mainly by expanding their number and
by prolonging their half-lives.
107
Clinical experience has
not shown negative effects on HIV-infected patients.
5. Antily mphocyte polyclonal antibodies: The use of these
drugs is controversial. Carter et al.
108
reported 11 HIV-
infected renal transplant recipients who received thymo-
globulin for acute rejection or delayed graft function.
Thymoglobulin produced profound and long-lasting
suppression of the CD4 þ T-cell count and was associated
with an increased risk of infecti ons requiring hospitaliza-
tion. In contrast, in another small series (three patients),
we observed that CD4 þ T-cell thymoglobulin-induced
lymphocytopenia was not associated with increased risk of
infection.
70
Stock et al.
74
found that patients who received
this therapy had about twice as many seriou s infections
per follow-up year as patients who did not receive such
therapy. In addition, the risks of death and of graft loss
were marginally higher for patients who received this
induction therapy. The authors recommend restricting
this therapy for patients at very high immunological risk
for rejection.
74
6. Monoclonal anti-CD20 antibody: There is a single
experience with one HIV-infected renal transplant reci-
pient who developed an acute humoral rejection that was
successfully treated w ith rituximab.
109
In the pre-cART era, the imm unosuppressive regimens
most frequently used were ‘azathioprine-corticosteroids’ and
cyclosporine-corticosteroids. Schwarz et al.
34
reported a
positive association between cyclosporine and improved
outcome in HIV-infected transplant recipients. Subsequent
observations have suggested that cyclosporine may attenuate
the course of HIV infection by inhibition of viral replica-
tion.
101
More recent series from the cART era have reported
different immunosuppressive regimens (Table 8), whi ch are
Table 7 | Antiretroviral drug regimens recommended among
HIV-infected renal transplant recipients
1. NRTIs
K A combination of two NRTIs (for example tenofovir plus
emtricitabine or abacavir plus lamivudine) can be used safely in
renal transplant recipients with dose adjusted to renal function.
K Tenofovir should be used with caution and close monitoring of
renal function.
K Abacavir should not be used in recipients receiving a kidney from
an HLA-B57*01-positive donor to avoid the potential risk of
hypersensitivity reaction to abacavir.
2. NNRTIs and protease inhibitors
K Can be used safely in combination with two NRTIs
K Important interactions with immunosuppressive drugs may
appear, mainly with protease inhibitors.
3. Novel classes of antiretrovirals
K Must be considered in combination with NRTIs
K Integrase inhibitors (raltegravir): have no interactions with
immunosuppressive agents at the CYP450 level.
K Entry inhibitors (enfuvirtide (T20)): could be an alternative in
combination with NRTIs, although subcutaneous administration
is a limitation.
K CCR5 co-receptor antagonists (maraviroc): a substrate of CYP450.
Its levels can be modified by inducers or inhibitors. Experimental
studies have suggested that maraviroc could have an important
role as an antirejection drug.
Abbreviations: CCR5, CC chemokine receptor 5; HIV, human immunodeficiency virus;
NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside/nucleotide
reverse transcriptase inhibitor.
Kidney International (2011) 79 , 825–842
833
JC Trullas et al.: Renal transplantation and HIV review
Page 9
not significantly different from those used in HIV-negative
renal transplant recipients.
9,56–74
Drug–drug interactions
Some pharmacological interactions between antiretrovirals
and immuno suppressants may be clinically relevant. Drug
interactions may require dosing modifications to maintain
appropriate drug levels and for this reason it is very
important to perform close therapeutic drug monitoring.
These interactions are summarized in Table 9.
110–129
Mycophenolate mofetil is metabolized mainly by glucur-
onidation in the liver. Atazanavir inhibits UDP-glucuronosyl
transferase and, theoretically, leads to an increase in blood
mycophenolate mofe til levels, whereas ritonavir induces
glucuronidation and could reduce blood mycophenolate
mofetil levels. However, clinically important drug–drug
interactions between mycophenolate mofetil and these
antiretroviral agents have not been reported. Mycophenolate
mofetil has inhibitory effects on HIV and is synerg istic with
abacavir, didanosine, and tenofovir.
102–104,118
Cyclosporine, tacrolimus, and sirolimus are metabolized
in the liver by cy tochrome P450 (isoenzyme 3A4). Anti-
retroviral drugs can act as inhibitors or inducers of these
enzymatic systems. When they act as inhibitors (for example,
protease inhibitors), they increase concentrations of the
immunosuppressive drugs, leadi ng to toxicity; therefore,
doses must be markedly reduced. Clinical experience
indicates that patients on protease inhibitors require only
1–2 mg of tacrolimus per week to maintain therapeutic
levels.
110–112
Stopping the protease inhi bitors while taking
calcineurin inhibitors could cause an acute rejection.
On the other hand, when antiretroviral drugs act as enzyme
inducers (for example, NNRTIs), they reduce drug levels
and can trigger rejection. Therefore, doses of immuno-
suppressive drugs must be increased.
113
Stopping the
NNRTI while taking calcineurin inhibitors could cause
toxicity.
In one of the largest series published, Frassetto et al.
114
recently described the pharmacokinetics and dosing mod-
ifications in 35 patients (20 kidney recipients, 13 liver
recipients, and 2 kidney–liver transplant recipients). Patients
receiving protease inhibitors had marked increases in
cyclosporine, tacrolimus, and sirolimus levels compared with
those on NNRTIs alone or with patients not on antiretroviral
treatment, and it was necessary to reduce the dose or increase
the dosing interval. Patients taking efavirenz required much
higher doses of cyclosporine than those using any other
antiretroviral drug.
In order to avoid these interactions, some researchers have
reported the use of enfuvirtide plus two N RTIs in liver
transplant recipients.
115
Theoretically, based on the elimina-
tion pathways, a pharmacokinetic drug–drug interaction with
the new CCR5 antagonist maraviroc is unlikely. Maraviroc is
a substrate of CYP3A4, but it is not an inducer or inhibitor of
CYP3A4. The HIV-1 integrase inhibitor raltegravir offers
important advantages: it has high antiviral potency and no
significant interactions with immunosuppressive agents,
because of its lack of effect on CYP3A4 (raltegrav ir is
primarily metabolized by the liver via glucuronidation and
not by CYP3A4).
116
Tricot et al.
75
recently observed no
Table 8 | Immunosuppressive regimens in HIV-infected renal transplant recipients in the cART period
Author (reference) N CyA FK AZA SRL MMF Corticosteroids
Basiliximab/
daclizumab ATG/OKT3
Abbott et al.
56
47 30 (68.2) 19 (43.2) 7 (15.9%) 38 (86.4) —/22 (46.8%)
Qiu et al.
57
38 20 (52%) 13 (34%) 14 (36.8%) 10 (26.3%)/6 (15%) 4 (10%)/3 (7.9%)
Kuo et al.
58
2 Preferred
a
Preferred
a
——
Stock et al.
59
6 Preferred
a
Preferred
a
Preferred
a
——
Roland et al.
60
26 Preferred
a
Preferred
a
——
Toso et al.
61
1 1 (100%) 1 (100%) 1 (100%) 1 (100%)/—
Kumar et al.
62
12 ND ND ND ND ND ND ND ND
Stock et al.
63
10 Preferred
a
Preferred
a
Preferred
a
——
Mazuecos et al.
64
10 10 (100%) 10 (100%) 10 (100%) 1 (10%)/—
b
Kumar et al.
65
40 40 (100%) 40 (100%) 40 (100%) 40 (100%)/—
Roland et al.
66
18 12 (66%) 5 (28%) 16 (89%) 6 (34%)/1 (5.5%)
Gruber et al.
67
8 8 (100%) 8 (100%) 8 (100%) 8 (100%)
Muller et al.
68
2 1 (50%) 1 (50%) 2 (100%) 2 (100%) ND ND
Ballarin et al.
69
1 1 (100%) 1 (100%) 1 (100%) 1 (100%)/—
Trullas et al.
70
3 1 (33%) 2 (67%) 3 (100%) 3 (300%) 3 (100%)/—
Trullas et al.
9
26
c
7 (32%) 15 (68%) 1 (4.5%) 19 (86%) 19 (86%) 3 (14%)/5 (23%) 5 (23%)/—
Billault et al.
72
7 7 (100%) 7 (100%) 7 (100%) —/7 (100%)
Touzot et al.
73
27 11 (41%) 16 (59%) 27 (100%) 27 (100%) 26 (97%)/— 1 (3%)/—
Stock et al.
74
150 33 (22%) 99 (66%)
d
131 (87%) 150 (100%) 76 (51%) 48 (32%)/—
Abbreviations: ATG, thymoglobulin; AZA, azathioprine; Corticosteroids, prednisone; cART, combined antiretroviral treatment; CyA, cyclosporine; FK, tacrolimus; HIV, human
immunodeficiency virus; MMF, mycophenolate mofetil; N, number of transplants; ND, no data available; OKT3, muromonab-CD3; SRL, sirolimus.
a
Immunosuppression regimens were based on these drugs, but the exact number of patients is not specified.
b
Anti CD-25 was used in 3 patients.
c
Data available for 22 patients.
d
SRL was used in patients with calcineurin inhibitor-associated nephrotoxicity.
834 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 10
episodes of acute rejection in five raltegravir-treated
HIV-infected renal transplant recipients.
Given the speed with which new antiretroviral drugs
emerge and thus generate previously unknown interactions,
clinicians should regularly consult updated databas es on drug
interactions and product information.
124–129
HCV coinfection
HCV coinfection is an important issue in settings were
intravenous drug use is the main risk factor for HIV
transmission.
HCV disease progresses more rapidly in HIV-infected
patients and in liver and kidney transplant recipients.
HCV-infected renal transplant recipients (especially those
with active replication) have higher morbidity and mor tality
related with infectious and hepatic complications.
130
There is
evidence that HCV-infected transplant recipients have a
significantly greater risk of chronic liver disease, proteinuria,
and chronic allograft nephropathy. Furthermore, patients
with viral replication and chronic elevated alanine amino-
transferase levels have an increased risk of death and
graft loss.
131
In the absence of severe chronic liver disease, patients on
dialysis with positive HCV RNA in plasma should be
evaluated for anti-HC V treatment with interferon before
transplantation. Between 30 and 50% of patients have
complete remission, and if a reactivation occurs in the
post-transplant period, the clinical course is less severe
when patients have previously received antiviral therapy.
Combination therapy with interferon and ribavirin is not
recommended in patients on dialysis because of the risk of
hemolysis.
132
Options for antiviral therapy in the post-
transplant period are limited. Interferon is not recom-
mended, because of the risk of acute renal rejection. There
is less experience with ribavirin in monotherapy. Ribavirin
lowers alanine aminotransferase levels but has no effect on
HCV viral load. The histopathological efficacy of ribavirin
alone in kidney allograft recipients with hepatitis C is
controversial. Some studies have shown ribavirin to be
associated with histological improvement,
133
and other
studies have shown no effect of ribavirin with histological
progression.
134
Because so many HIV-infected patients with ERSD also
have HCV infection, it is important to determine whether
renal transplantation is effective in these patients. It is
unknown if the outcome of HCV/HIV-coinfected renal
transplant recipients would be worse than for patients
without HIV infection. In addition, there is not enough
experience to assess the efficacy and safety of interferon and/
or ribavirin treatment in HCV/HIV-coinfected transplant
recipients.
Cardiovascular diseases
As the use of cART became widespread, there has been an
increase in the incidence of non-HIV-related diseases in
HIV-infected patients. These include diabetes mellitus,
hypertension, and other cardiovascular diseases, directly
related—in part—with antiretroviral treatment. In addition,
cardiovascular diseases represent the first cause of death in
renal transplant recipients who survive in the long term.
135
Therefore, blood pressure and glucose and cholesterol levels
should be closely monitored to improve long-term sur vival,
not only in the HIV-infected population, but esp ecially in
HIV-infected renal transplant recipients.
136
Ethical issues
Organ transplantation in HIV-infected patients has raised
ethical problems that have not yet been completely solved.
However, with growing experience and encouraging results,
most groups agree that HIV-infected patients with ESRD
should be evaluated for inclusion on the renal transplanta-
tion waiting list.
137
PANCREAS–KIDNEY TRANSPLANTATION IN HIV-INFECTED
PATIENTS
There is relatively little experience with simultane ous
pancreas–kidney transplantation in HIV-infected patients
with diabetes mellitus. Preliminary experience suggests that
pancreas–kidney transplantations can be performed using the
same criteria as for kidney transplantation. However, there is
a higher risk of procedure-related infectious complica-
tions.
61,138,139
THE NEXT STEP
Several issues must be clarifie d in the coming years, which
are as follows: (1) the most appropriate combination of
immunosuppressive and antiretroviral drugs must be estab-
lished in terms of clinical efficacy, low acute rejection rate,
absence of nephrotoxicity, appropriate safety profile, minimal
pharmacological interactions, and sustained virological
suppression; (2) knowledge of the pathogenesis of acute
rejection should be expanded; (3) the most appropriate
strategy for the management of HCV/HIV-coinfected
patients must be decided; and (4) physicians should be
aware of the clinical course of HIV infection in patients
receiving long-term immunosuppression.
CONCLUSIONS
1. Renal transplantation waiting list: All HIV-infected
patients with ESRD should be considered candidates for
renal transplantation if they meet the HIV inclusion
criteria.
2. Patient and graft survival: There are enough data to affirm
that renal transplantation in adequately selected HIV-
infected patie nts is a safe procedure in the short and
medium term, with patient and graft survival rates simil ar
to those of HIV-negative renal transplant recipients.
3. Acute rejection: In comparison with the HIV-negative
population, HIV-infected patients have a high rate of
acute rejection. The use of antiretroviral drugs that do not
react with immunosuppressive drugs may reduce the risk
of acute rejection.
Kidney International (2011) 79 , 825–842 835
JC Trullas et al.: Renal transplantation and HIV review
Page 11
Table 9 | Drug interactions between antiretroviral agents and immunosuppressive drugs
a
Antiretroviral agents
b
NRTI (abacavir, ddI,
FTC, 3TC, d4T, AZT, TDF) NNRTI (NVP, EFV, and etravirine)
PI (APV, ATV, FPV, DRV, IDV, LPV/r, NFV, RTV,
SQV, TPV/r)
CCR5 co-receptor
antagonists (maraviroc)
Integrase inhibitors
(raltegravir)
Azathioprine No drug–drug interactions between azathioprine and antiretroviral agents have been described. Caution is advised when azathioprine is used with other agents affecting
myelopoiesis, including co-trimoxazole.
Basiliximab Basiliximab is an immunoglobulin; therefore no metabolic drug–drug interactions with antiretrovirals are to be expected.
Cyclosporine
c,d
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely.
As emtricitabine, lamivudine,
and tenofovir are excreted
mainly via the kidneys,
nephrotoxic drugs could impair
its elimination.
Tenofovir: Increased risk of
nephrotoxicity
NNRTI: may require an increase in
CyA dosage.
EFV: some patients needed an initial
CyA dose of 350–450 mg every 12 h,
followed by a maintenance dose of
250–400 mg every 12 h.
NVP: some patients needed an
initial dose of 200250 mg every
12 h of CyA, followed by a
maintenance dose of 100–175 mg
every 12 h.
TDM of CyA is recommended
Risk of increased drug levels/toxicity of
immunosuppressive drugs. Markedly lower doses
of immunosuppressive drugs may be required.
e
With IDV some patients needed an initial CyA
dose of 75–100 mg every 12 h followed by a
maintenance dose of 75 mg every 12 h.
With LPV/r some patients needed an initial dose of
CyA of 25 mg every 12 h followed by a
maintenance dose of 25 mg every 24–48 h.
With NFV some patients needed an initial dose of
CyA of 50–75 mg every 12 h, followed by a
maintenance dose of 25 mg every 12 h.
In the study by Guaraldi et al.
117
(including 12
patients who underwent liver transplantation), the
mean fold decrease in the dosage of
immunosuppressive drug (CyA, FK, SRL) that was
necessary to maintain therapeutic windows was
8.75 (range 8–14) after initiating boosted PIs, and
3 (range 2–4) after initiating unboosted PIs.
TPV/r concentrations of cyclosporine
cannot be predicted, due to conflicting
effect on CYP3A (inhibition) and P-gp
(significant inhibition after the first dose,
but slight induction at steady state). TDM of
CyA is recommended
e
Theoretically, based on the
elimination pathways, it is
unlikely that maraviroc
could modify blood CyA
levels
d
Theoretically, based on
the elimination
pathways, a
pharmacokinetic
drug–drug interaction is
unlikely
Daclizumab Daclizumab is an immunoglobulin; therefore, no metabolic drug–drug interactions with antiretrovirals are to be expected.
Everolimus
c,d
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
Inducers of CYP3A4 like NNRTI may
increase the metabolism of
everolimus and decrease blood
everolimus levels.
TDM of everolimus is
recommended
Moderate inhibitors of CYP3A4 and P-gp such as
PIs may increase everolimus blood levels
With TPV/r, concentrations of everolimus cannot
be predicted, due to the conflicting effect on
CYP3A (inhibition) and P-gp (slight induction at
steady state)
TDM of everolimus is recommended
Theoretically, based on the
elimination pathways, it is
unlikely that maraviroc
could modify blood
everolimus levels
d
Theoretically, based on
the elimination
pathways, a
pharmacokinetic
drug–drug interaction is
unlikely
Methylprednisolone Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
Theoretically, inducers of CYP3A4
such as NNRTI may increase the
metabolism of corticosteroids and
decrease blood levels
Theoretically, inhibitors of CYP3A4 like PIs may
decrease the metabolism of corticosteroids and
increase blood levels (iatrogenic Cushing’s
syndrome has been described as a result of an
interaction between ritonavir and inhaled
fluticasone)
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
Theoretically, based on
the elimination
pathways, a
pharmacokinetic
drug–drug interaction is
unlikely
Table 9 continued on following page
836 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 12
Table 9 | Continued
Antiretroviral agents
b
NRTI (abacavir, ddI,
FTC, 3TC, d4T, AZT, TDF) NNRTI (NVP, EFV, and etravirine)
PI (APV, ATV, FPV, DRV, IDV, LPV/r, NFV, RTV,
SQV, TPV/r)
CCR5 co-receptor
antagonists (maraviroc)
Integrase inhibitors
(raltegravir)
Muromonab CD3
(OKT3)
Muromonab CD3 is an immunoglobulin; therefore, no metabolic drug–drug interactions with antiretrovirals are to be expected.
Mycophenolate Abacavir, zidovudine, and
mycophenolate mofetil are
eliminated mainly by
glucuronidation; therefore, an
interaction cannot be ruled out.
However, clinically important
drug–drug interactions have not
been reported.
Mycophenolate has inhibitory
effects on HIV and is synergistic
with abacavir, didanosine, and
tenofovir.
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction with other NRTI is
unlikely
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
Mycophenolate mofetil is metabolized mainly by
glucuronidation. ATV inhibits UDP-glucuronosyl
transferase (UGT) (an increase in mycophenolate
blood levels would be expected), whereas RTV
(and boosted PI including TPV/r) and NFV increase
glucuronidation (a decrease in blood
mycophenolate mofetil levels would be
expected). However, clinically important
drug–drug interactions between mycophenolate
mofetil and these antiretroviral agents have not
been reported.
Theoretically, based on the elimination pathways,
a pharmacokinetic drug–drug interaction with
other PIs is unlikely
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
Theoretically, based on
the elimination
pathways, a
pharmacokinetic
drug–drug interaction is
unlikely
Sirolimus
c,d
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
Inducers of CYP3A4 like NNRTI may
increase the metabolism of
sirolimus and decrease blood
sirolimus levels.
TDM of SRL is recommended
Risk of increased drug levels/toxicity of
immunosuppressive drugs. Markedly lower doses
of immunosuppressive drugs may be required.
f
In the study by Guaraldi et al.
117
(including 12
patients who underwent liver transplantation), the
mean fold decrease in immunosuppressive drug
(FK, CyA, SRL) dosage that was necessary to
maintain therapeutic windows was 8.75 (range
8–14) after initiating boosted PIs, and 3 (range 2–4)
after initiating unboosted PIs.
With TPV/r the concentrations of sirolimus cannot be
predicted, due to a conflicting effect on CYP3A
(inhibition) and P-gp (slight induction at steady state).
TDM of SRL is recommended
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely
d
Theoretically, based on
the elimination
pathways, a
pharmacokinetic
drug–drug interaction is
unlikely
Tacrolimus
c,d
Theoretically, based on the
elimination pathways, a
pharmacokinetic drug–drug
interaction is unlikely.
As emtricitabine, lamivudine,
and tenofovir are primarily
excreted via the kidneys,
nephrotoxic drugs could impair
their elimination
Inducers of CYP3A4 such as NNRTI
may increase the metabolism of
tacrolimus and decrease blood
tacrolimus levels.
TDM of FK is recommended.
Risk of increased drug levels/toxicity of
immunosuppressive drugs. Markedly lower doses
of immunosuppressive drugs may be required.
With LPV/r some patients needed an initial dose of
FK of 0.5 mg every 12 h, followed by a
maintenance dose of 0.5 mg every 48 h to 1 mg
once weekly or even less. When LPV/r is initiated
in a patient on FK, the next FK dose may need to
be delayed for between 3 and 5 weeks,
depending on hepatic function
Theoretically, based on the
elimination pathways, it is
unlikely that maraviroc
could modify blood
tacrolimus levels
d
Theoretically, based on
the elimination
pathways, a
pharmacokinetic
drug–drug interaction is
unlikely
Table 9 continued on following page
Kidney International (2011) 79 , 825–842 837
JC Trullas et al.: Renal transplantation and HIV review
Page 13
Table 9 | Continued
Antiretroviral agents
b
NRTI (abacavir, ddI,
FTC, 3TC, d4T, AZT, TDF) NNRTI (NVP, EFV, and etravirine)
PI (APV, ATV, FPV, DRV, IDV, LPV/r, NFV, RTV,
SQV, TPV/r)
CCR5 co-receptor
antagonists (maraviroc)
Integrase inhibitors
(raltegravir)
Tenofovir: Increased risk of
nephrotoxicity
With NFV some patients needed an initial dose of
FK of 1 mg every 12 h, followed by a maintenance
dose of 0.5 mg every 24–48 h or even less (40–70-
fold dose reduction).
In the study by Guaraldi et al.
117
(including 12
patients who underwent liver transplantation), the
mean fold decrease in immunosuppressive drug
(FK, CyA, SRL) dosage that was necessary to
maintain therapeutic windows was 8.75 (range
8–14) after initiating boosted PIs, and 3 (range 2–4)
after initiating unboosted PIs.
TPV/r: concentrations of tacrolimus cannot be
predicted, due to a conflicting effect on CYP3A
(inhibition) and P-gp (slight induction at steady
state)
TDM of FK is recommended
Thymoglobulin Thymoglobulin is an immunoglobulin; therefore, no metabolic drug–drug interactions with antiretrovirals are to be expected
Abbreviations: 3TC, lamivudine; APV, amprenavir; ATV, atazanavir; AZT, zidovudine; CyA, cyclosporine A; CYP, cytochrome P450; d4T, stavudine; ddI, didanosine; DRV, darunavir; EFV, efavirenz; FK, tacrolimus; FPV, fosamprenavir;
FTC, emtricitabine; IDV, indinavir; LPV/r, lopinavir/ritonavir; MFL, mycophenolate mofetil; NFV, nelfinavir; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside analog; NVP, nevirapine; P-gp, P glycoprotein;
PI, protease inhibitor; RTV, ritonavir; SQV, saquinavir; SRL, sirolimus; TDF, tenofovir; TDM, therapeutic drug monitoring; TPV, tipranavir; UGT, UDP-glucuronosyl transferase.
a
It is very important to maintain good adherence to therapy due to drug–drug interactions. If a cytochrome P450 inhibitor is suddenly withdrawn and immunosuppressive dosage is not properly increased, a transplant rejection
may occur. On the other hand, if a cytochrome P450 inducer is suddenly withdrawn and immunosuppressive dosage is not properly decreased, toxicity may occur.
b
Enfuvirtide: theoretically, based on the elimination pathways, a pharmacokinetic drug–drug interaction with immunosuppressive drugs is unlikely.
c
Cyclosporine, everolimus, tacrolimus, and sirolimus are extensively metabolized by cytochrome CYP3A. Substances that inhibit this enzyme (such as clarithromycin, diltiazem, erythromycin, fluoxetine, fluvoxamine, grapefruit
juice, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, paroxetine, telithromycin, and voriconazole) could decrease metabolism and increase blood concentrations of these immunosuppressive drugs. On the other
hand, substances that are inducers of CYP3A activity (such as carbamazepine, efavirenz, Hypericum perforatum (St John’s wort), nevirapine, phenobarbital, phenytoin, rifampin, or rifabutin) could increase the metabolism of
immunosuppressive drugs and decrease blood levels. The manufacturers of sirolimus and everolimus do not recommend co-administration with strong inhibitors of CYP3A4 or inducers of CYP3A4. Cyclosporine, everolimus,
tacrolimus, and sirolimus are also substrates for the multidrug efflux pump, P-glycoprotein (P-gp) located in the small intestine. Inhibitors of P-gp, such as PIs, may decrease the efflux of these immunosuppressive drugs
from intestinal cells and increase blood levels.
d
Some of these immunosuppressive drugs inhibit some human liver microsomal enzymes. In vitro, everolimus was a competitive inhibitor of CYP3A4 and of CYP2D6; therefore, a potential increase in concentrations of
antiretroviral agents eliminated by these enzymes (like PI, NNRTI, and maraviroc) could not be excluded. Sirolimus inhibits CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 in vitro; nevertheless, the sirolimus concentrations necessary to
produce inhibition are much higher than those observed in patients receiving therapeutic doses, and therefore it is not expected to inhibit the activity of these isoenzymes in vivo. Cyclosporine and tacrolimus are moderate
inhibitors of CYP3A4 and may also inhibit P-gp, and therefore an increase in blood levels of some antiretrovirals (PIs, NNRTI, maraviroc) cannot be excluded. An inhibitory effect of maraviroc on P-gp cannot be excluded, even it
has not been evaluated. As cyclosporine, tacrolimus, sirolimus, and everolimus are substrates of P-gp, an increase in blood levels of these drugs could be theoretically expected if an inhibitory effect of maraviroc on P-gp is
confirmed.
e
The antiretroviral is an inhibitor of the P450 isoform CYP3A, which is the primary elimination pathway of CyA, everolimus, FK, and SRL. Co-administration with the antiretroviral may result in increased plasma concentrations
of these immunosuppressive drugs. Patients on protease inhibitors require markedly lower doses of cyclosporine, with continued lowering of the cyclosporine dose over time and ongoing cyclosporine trough monitoring
because of progressively increasing cyclosporine bioavailability.
f
Even with one-fifth of the recommended dose of NFV (250 mg/12 h), a ninefold increase in the sirolimus trough concentration, threefold increase in peak concentration, and 60% increase in the area under the concentration
curve 0–24 h have been observed in a liver transplantation patient, compared with patients who were not on NFV.
838 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 14
4. Course of HIV infection: Immunosuppressive therapy
does not have a negative impact on the course of HIV
infection, with no evidence of progression to AIDS and no
further opportunistic infections or neoplasms. Patients
should follow the same prophylaxis protocols as the non-
HIV-infected populati on.
5. Immunosuppression: The best immunosuppressive regi-
men in HIV-infected renal transplant recipients has not
been completely established. Until results from larger and
controlled studies are available, immunosuppressiv e therapy
in the early post-transplant period should include induction
therapy with anti-interleukin-2 receptor monoclonal anti-
bodies (basiliximab) in combination with triple therapy
based on calcineurin inhibitors (cyclosporine or tacroli-
mus), myc ophenolate mofetil, and corticosteroids. There is
little experience with sirolimus, but it does not seem to have
negative effects. The use of antilymphocyte polyclonal
antibodies is not contraindicated, but pr oduc es deep and
persistent lymphocytopenia that must be closely monitored.
This treatment is not recommended in patients with high
viral replication or previous lymphocytopenia.
6. Antiretro viral regimens: Dose adjustment is mandatory for
some antiretro viral drugs. Physic ians must be awar e of
interactions between immunosuppressive agents and anti-
retroviral drugs, especially protease inhibitors and, to a lesser
extent NNR TIs. For this reason, it is very important to
closely monitor immunosuppressive drugs and, when
possible, antiretroviral drugs (NR TIs, protease inhibitors,
and raltegravir). Antiretroviral regimens containing drugs
with a low pharmac ological interaction profile (for example,
raltegravir plus two NRTI s) are recommended.
7. HCV coinfection: There is little experience in the
management and outcome of HCV/HIV-coinfected
patients in the pre- and post-transplan t period.
8. Multidisciplinary management: Evaluation and pre- and
post-transplant management should include interdisci-
plinary teams comprising nephrologists, urologists,
infectious diseases and HIV special ists, psychologists,
social workers, and members of alcohol and other drug
detoxification programs.
DISCLOSURE
All the authors declared no competing interests.
ACKNOWLEDGMENTS
This study was partially supported by the ‘Red Tema
´
tica Cooperativa
de Grupos de Investigacio
´
n en Sida of the Fondo de Investigacio
´
n
Sanitaria (FIS)’ (ISCIII-RETIC RD06/006) from the Instituto de Salud
Carlos III, Madrid (Spain) and the ‘Fundacio
´
n para la Investigacio
´
ny
Prevencion del Sida en Espan
˜
a (FIPSE grant 0858-09)’ Madrid (Spain).
JMM received a Research Grant from the ‘Institut d’
Investigacions Biome
`
diques August Pi i Sunyer (IDIBAPS).’
REFERENCES
1. Mocroft A, Brettle R, Kirk O et al. Changes in the cause of death among
HIV positive subjects across Europe: results from the EuroSIDA study.
AIDS 2002; 16: 1663–1671.
2. Miro JM, Aguero F, Laguno M et al. Liver transplantation in HIV/hepatitis
co-infection. J HIV Ther 2007; 12: 24–35.
3. Landin L, Rodriguez-Perez JC, Garcia-Bello MA et al. Kidney transplants in
HIV-positive recipients under HAART. A comprehensive review and
meta-analysis of 12 series. Nephrol Dial Transplant 2010; 25:
3106–3115.
4. Daugas E, Rougier JP, Hill G. HAART-related nephropathies in
HIV-infected patients. Kidney Int 2005; 67: 393–403.
5. Ro
¨
ling J, Schmid H, Fischereder M et al. HIV-associated renal diseases
and highly active antiretroviral therapy-induced nephropathy. Clin Infect
Dis 2006; 42: 1488–1495.
6. Kimmel PL, Barisoni L, Kopp JB. Pathogenesis and treatment of
HIV-associated renal diseases: lessons from clinical and animal
studies, molecular pathologic correlations, and genetic investigations.
Ann Intern Med 2003; 139: 214–226.
7. Atta MG, Gallant JE, Rahman MH et al. Antiretroviral therapy in the
treatment of HIV-associated nephropathy. Nephrol Dial Transplant 2006;
21: 2809–2813.
8. Atta MG, Fine DM, Kirk GD et al. Survival during renal replacement
therapy among African Americans infected with HIV type 1 in urban
Baltimore, Maryland. Clin Infect Dis 2007; 45: 1625–1632.
9. 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.
10. Finelli L, Miller JT, Tokars JI et al. National surveillance of dialysis-
associated diseases in the United States, 2002. Semin Dial 2005; 18:
52–61.
11. Rao TKS. Acquired immunodeficiency syndrome (AIDS), human
immunodeficiency virus (HIV), and dialysis. In: Andreucci VE, Fine LG
(eds). International Yearbook of Nephrology 1991. Kluwer Academic:
Boston, 1990, pp 199–218.
12. Geerlings W, Tufveson G, Brunner FP et al. Combined report on regular
dialysis and transplantation in Europe, XXI, 1990. Nephrol Dial Transplant
1991; 6(Suppl 4): 5–29.
13. Barbiano di Belgiojoso G, Trezzi M, Scorza D et al. HIV infection in dialysis
centers in Italy: a nationwide multicenter study. J Nephrol
1998; 11:
249–254.
14. Poignet JL, Desassis JF, Chanton N et al. Prevalence of HIV infection in
dialysis patients: results of a national multicenter study. Nephrologie
1999; 20: 159–163.
15. Vigneau C, Guiard-Schmid JB, Tourret J et al. The clinical characteristics
of HIV-infected patients receiving dialysis in France between 1997 and
2002. Kidney Int 2005; 67: 1509–1514.
16. Barril G, Trulla
´
s JC, Gonza
´
lez-Parra E et al. Prevalence of HIV-1-infection
in dialysis units in Spain and potential candidates for renal
transplantation: results of a Spanish survey. Enferm Infecc Microbiol Clin
2005; 23: 335–339.
17. Trulla
`
s JC, Barril G, Cofan F et al. Prevalence and clinical characteristics of
HIV-1-infected patients receiving dialysis in Spain: results of a Spanish
survey in 2006. AIDS Res Hum Retroviruses 2008; 24: 1229–1235.
18. Hassan NF, el Ghorab NM, Abdel Rehim MS et al. HIV infection in
renal dialysis patients in Egypt. AIDS 1994; 8: 853.
19. Morikawa K, Kuroda M, Tofuku Y et al. Prevalence of ATLV and HIV
among hemodialysis patients in Japan. Nephron 1988; 50: 77–78.
20. Falcao HA, Rebelo M. Anti -HIV antibodies in population of 132 patients
in hemodialysis (Abstract). Xth International Congress of Nephrology:
London, 1987.
21. Ortiz C, Meneses R, Jaffe D et al. Outcome of patients with human
immunodeficiency virus on maintenance hemodialysis. Kidney Int 1988;
34: 248–253.
22. Ahuja TS, Grady J, Khan S. Changing trends in the survival of dialysis
patients with human immunodeficiency virus in the United States.
J Am Soc Nephrol 2002; 13: 1889–1893.
23. Trulla
`
s JC, Barril G, Cofan F et al. Outcome and Prognostic Factors in
HIV-1-Infected Dialysis Patients in Spain in the HAART Era: A Case-Control
GESIDA/SEN Study. 17th CROI (Conference on Retroviruses and
Opportunistic Infections, San Francisco, 2010. Abstract 739.
24. Rodriguez RA, Mendelson M, O’Hare AM et al. Determinants of survival
among HIV-infected chronic dialysis patients. J Am Soc Nephrol 2003; 14:
1307–1313.
25. Tourret J, Tostivint I, du Montcel ST et al. Outcome and prognosis factors
in HIV-infected hemodialysis patients. Clin J Am Soc Nephrol 2006; 1:
1241–1247.
26. Choi AI, Rodriguez RA, Bacchetti P et al. Low rates of antiretroviral
therapy among HIV-infected patients with chronic kidney disease.
Clin Infect Dis 2007; 45: 1633–1639.
Kidney International (2011) 79 , 825–842 839
JC Trullas et al.: Renal transplantation and HIV review
Page 15
27. Solid Organ Transplantation in HIV: Multi-Site Study [Last accessed
19 August 2010]. Available at: www.hivtransplant.com.
28. Anonymous. Solid organ transplantation in the HIV-infected patient.
Am J Transplant 2004; 4(Suppl 10): 83–88.
29. Miro JM, Torre-Cisneros 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.
30. Bhagani S, Sweny P, Brook G. Guidelines for kidney transplantation in
patients with HIV disease. HIV Med 2006; 7: 133–139.
31. Grossi P, Tumietto F, Costigliola P et al. Liver transplantation in
HIV-infected individuals: results of the Italian national program.
Transplantation 2006; 82(Suppl 2): 446.
32. Epstein AM, Ayanian JZ, Keogh JH et al. Racial disparities in access
to renal transplantationclinically appropriate or due to underuse or
overuse? N Engl J Med 2000; 343: 1537–1544.
33. Sawinski D, Wyatt CM, Casagrande L et al. Factors associated with failure
to list HIV-positive kidney transplant candidates. Am J Transplant 2009;
9:15.
34. Schwarz A, Offermann G, Keller F et al. The effect of cyclosporine
on the progression of human immunodeficiency virus type 1 infection
transmitted by transplantation–data on four cases and review of the
literature. Transplantation 1993; 55: 95–103.
35. Trulla
´
s JC, Miro
´
JM, Barril G et al. Renal transplantation in patients with
HIV infection. Enferm Infecc Microbiol Clin 2005; 23: 363–374.
36. Feduska NJ, Perkins HA, Melzer J et al. Observations relating to the
incidence of the acquired immune deficiency syndrome and other
possibly associated conditions in a large population of renal transplant
recipients. Transplant Proc 1987; 19: 2161–2166.
37. Kumar P, Pearson JE, Martı
´
nDHet al. Transmission of human
immunodeficiency virus by transplantation of a renal allograft, with
development of the acquired immunodeficiency syndrome. Ann Intern
Med 1987; 106: 244–245.
38. Imbasciati E, De Cristofaro V, Sama F et al. Acquired immunodeficiency
syndrome transmitted by transplanted kidney: clinical course
during maintenance haemodialysis. Nephrol Dial Transplant 1988; 3:
681–683.
39. Milgrom M, Esquenazi V, Fuller L et al. Acquired immunodeficiency
syndrome in a transplant patient. Transplant Proc
1985; 17(Suppl 2): 75.
40. Lang P, Buisson C, Foucher A et al. Unusual immune deficiency
syndrome associated with LAV/HTLV-III in a kidney transplant recipient.
Transplant Proc 1986; 18: 1400.
41. Poli F, Scalamonga M, Pizzi C et al. HIV infection in cadaveric renal
allograft recipients in the North Italy Transplant Program.
Transplantation 1989; 47: 724–725.
42. Erice A, Rhame FS, Heussner RC et al. HIV infection in patients with
solid-organ transplants: report of five cases and review. Rev Infect Dis
1991; 13: 537–547.
43. Prompt CA, Reis MM, Grillo FM et al. Transmission of AIDS virus at renal
transplantation. Lancet 1985; 2: 672.
44. L’age-Stehr J, Schwarz A, Offermann G et al. HTLV-III infection in kidney
transplant recipients. Lancet 1985; 2: 1361–1362.
45. Schwarz A, Hoffmann F, L’age-Stehr J et al. Human immunodeficiency
virus transmission by organ donation. Outcome in cornea and kidney
recipients. Transplantation 1987; 44: 21–24.
46. Margreiter R, Fuchs D, Hausen A et al. HIV infection in renal allograft
recipients. Lancet 1986; 2: 398.
47. Briner V, Zimmerli W, Cathomas G et al. HIV infection caused by kidney
transplant: case report and review of 18 published cases. Schweiz Med
Wochenschr 1989; 119: 1046–1052.
48. Ahuja TS, Zingman B, Glicklich D. Long-term survival in an HIV-infected
transplant recipient. Am J Nephrol 1997; 17: 480–482.
49. Simonds RJ, Holmberg SD, Hurwitz RL et al. Transmission of human
immunodeficiency virus type 1 from a seronegative organ and tissue
donor. N Engl J Med 1992; 326: 726–732.
50. Bowen PA, Lobel SA, Caruana RJ et al. Transmission of human
immunodeficiency virus (HIV) by transplantation: clinical aspects and
time course analysis of viral antigenemia and antibody production.
Ann Intern Med 1988; 108: 46–48.
51. Ward JW, Schable C, Dickinson GM et al. Acute human
immunodeficiency virus infection. Antigen detection and
seroconversion in immunosuppressed patients. Transplantation 1989;
47: 722–724.
52. Kerman RH, Flechner SM, Van Buren CT et al. Investigation of human
T-lymphotropic virus III serology in a renal transplant population.
Transplant Proc 1987; 19: 2172–2175.
53. Carbone LG, Cohen DJ, Hardy MA et al. Determination of acquired
immunodeficiency syndrome (AIDS) after renal transplantation.
Am J Kidney Dis 1988; 11: 387–392.
54. Tzakis AG, Cooper MH, Dummer JS et al. Transplantation in HIV+
patients. Transplantation 1990; 49: 354–358.
55. Swanson SJ, Kirk AD, Ko CW et al. Impact of HIV seropositivity on graft
and patient survival after cadaveric renal transplantation in the United
States in the pre highly active antiretroviral therapy (HAART) era: an
historical cohort analysis of the United States Renal Data System.
Transpl Infect Dis 2002; 4: 144–147.
56. Abbott KC, Swanson SJ, Agodoa LY et al. Human immunodeficiency
virus infection and kidney transplantation in the era of highly active
antiretroviral therapy and modern immunosuppression. JAmSoc
Nephrol 2004; 15: 1633–1639.
57. Qiu J, Terasaki PI, Waki K et al. HIV-positive renal recipients can achieve
survival rates similar to those of HIV-negative patients. Transplant ation
2006; 81: 1658–1661.
58. Kuo PC, Stock PG. Transplantation in the HIV+ patient. Am J Transplant
2001; 1: 13–17.
59. Stock P, Roland M, Carlson L et al. Solid organ transplantation in
HIV-positive patients. Transplant Proc 2001; 33: 3646–3648.
60. Roland ME, Stock PG. Review of solid-organ transplantation in
HIV-infected patients. Transplantation 2003; 75: 425–429.
61. Toso C, Berney T, Oberholzer J et al. Kidney-pancreas transplantation in
a long-term non-progressor HIV-infected recipient. Am J Transplant
2003; 3: 631–633.
62. Kumar AM, Damask A, Roland M et al. Kidney transplantation in
HIV positive end stage renal disease patients-a prospective study.
Am J Transplant 2002; 2: 174.
63. Stock PG, Roland ME, Carlson L et al. Kidney and liver transplantation
in human immunodeficiency virus-infected patients: a pilot safety and
efficacy study. Transplantation 2003; 76: 370–375.
64. Mazuecos A, Pascual J, Go
´
mez E et al. Renal transplantation in
HIV-infected patients in Spain. Nefrologia 2006; 26: 113–120.
65. Kumar MS, Sierka DR, Damask AM et al. Safety and success of kidney
transplantation and concomitant immunosuppression in HIV-positive
patients. Kidney Int 2005; 67: 1622–1629.
66. 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.
67. Gruber SA, Doshi MD, Cincotta E et al. Preliminary experience with renal
transplantation in HIV+ recipients: low acute rejection and infection
rates. Transplantation 2008; 86: 269–274.
68. Mu
¨
ller NJ, Furrer H, Kaiser L et al. HIV and solid organ transplantation:
the Swiss experience. Swiss Med Wkly 2006; 136: 194–196.
69. Ballarin R, Di Benedetto F, Masetti M et al. Combined liver-kidney
transplantation in an HIV-HCV-coinfected patient with haemophilia.
AIDS 2008; 22: 2047–2049.
70. Trullas JC, Cofan F, Cocchi S et al. Effect of thymoglobulin induction
on HIV-infected renal transplant recipients: differences between
HIV-positive and HIV-negative patients. AIDS Res Hum Retroviruses 2007;
23: 1161–1165.
71. Mazuecos A, Ferna
´
ndez A, Andre
´
sAet al. Infeccio
´
n VIH y trasplante
renal: un estudio de casos y controles en Espan
˜
a. 1er Congreso
de la Sociedad Espan
˜
ola de Trasplante: Sevilla; 2-5 Junio 2010.
Abstract no. 68.
72. Billault C, Duvivier C, Valantin MA et al. Kidney transplantation in
HIV-positive patients: report of our first 7 cases. Transplant Proc 2009;
41: 3301–3304.
73. Touzot M, Pillebout E, Matignon M et al. Renal transplantation in
HIV-infected patients: the Paris experience. Am J Transplant 2010; 10:
2263–2269.
74. Stock PG, Barin B, Murphy B et al. Outcomes of kidney transplantation
in HIV-infected recipients. N Engl J Med 2010; 363: 2004–2201.
75. 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; 9:17.
76. Schnickel GT, Bastani S, Hsieh GR et al. Combined CXCR3/CCR5 blockade
attenuates acute and chronic rejection. J Immunol 2008; 180:
4714–4721.
77. Fischereder M, Luckow B, Hocher B et al. CC chemokine receptor 5 and
renal-transplant survival. Lancet 2001; 357: 1758–1761.
78. Gupta SK, Eustace JA, Winston JA et al. Guidelines for the management
of chronic kidney disease in HIV-infected patients: recommendations of
the HIV Medicine Association of the Infectious Diseases Society of
America. Clin Infect Dis 2005; 40: 1559–1585.
840 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 16
79. Panel de expertos de Gesida; Plan Nacional sobre el Sida. AIDS Study
Group/Spanish AIDS Plan consensus document on antiretroviral therapy
in adults with human immunodeficiency virus infection (updated
January 2010). Enferm Infecc Microbiol Clin 2010; 28: 362.e1–362.e91.
80. Antiretroviral agents product information. European Medicines Agency
(EMEA). EPARs for authorised medicinal products for human use
Available at: http://www.emea.europa.eu/htms/human/epar/a.htm
(accessed 10 March 2010).
81. Thompson MA, Aberg JA, Cahn P et al. Antiretroviral treatment of
adult HIV infection: 2010 recommendations of the International AIDS
Society-USA panel. JAMA 2010; 304: 321–333.
82. Gupta SK, Rosenkranzb SL, Cramerb YS et al. The pharmacokinetics and
pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected
persons requiring hemodialysis. AIDS 2008; 22: 1919–1927.
83. Guardiola JM, Mangues MA, Domingo P et al. Indinavir
pharmacokinetics in haemodialysis-dependent end-stage renal failure.
AIDS 1998; 12: 1395.
84. Jayasekara D, Aweeka FT, Rodriguez R et al. Antiviral therapy for HIV
patients with renal insufficiency. J Acquir Immune Defic Syndr 1999; 21:
384–395.
85. Paci-Bonaventure S, Hafi A, Vincent I et al. Lack of removal of nelfinavir
during a haemodialysis session in an HIV-1 infected patient with hepatic
and renal insufficiency. Neph rol Dial Transplant 2001; 16: 642–643.
86. Kearney BP, Yale K, Shah J et al. Pharmacokinetics and dosing
recommendations of tenofovir disoproxil fumarate in hepatic or renal
impairment. Clin Pharmacokinet 2006; 45: 1115–1124.
87. Chen L, Sabo JP, Philip E et al. Steady-state disposition of the
nonpeptidic protease inhibitor tipranavir when coadministered with
ritonavir. Antimicrob Agents Chemother 2007; 51: 2436–2444.
88. Gill MJ, Ostrop NJ, Fiske WD et al. Efavirenz dosing in patients
receiving continuous ambulatory peritoneal dialysis. AIDS 2000; 14:
1062–1064.
89. Izzedine H, Launay-Vacher V, Jullien V et al. Pharmacokinetics
of tenofovir in haemodialysis. Nephrol Dial Transplant 2003; 18:
1931–1933.
90. King JR, Acosta EP. Tipranavir: a novel nonpeptidic protease inhibitor
of HIV. Clin Pharmacokinet 2006; 45: 665–682.
91. Tebas P, Bellos N, Lucasti C et al. Enfuvirtide does not require dose
adjustment in patients with chronic kidney failure: results of a
pharmacokinetic study of enfuvirtide in HIV-1-infected patients with
impaired kidney function. J Acquir Immune Defic Syndr 2008; 47:
342–345.
92. Agarwala S, Eley T, Child M et al. Pharmacokinetics of atazanavir in
severely renally impaired subjects including those on hemodialysis. 8th
International Workshop on Clinical Pharmacology of HIV Therapy.
Budapest, Hungary, 16–18 April, 2007. Abstract 2.
93. Petry S, Hanley WD, Silk G et al. Effect of severe renal insufficiency on
raltegravir pharmacokinetics. 47th Interscience Conference on
Antimicrobial Agents and Chemotherapy, Chicago, 2007. Abstract
A-1424.
94. McIntyre J, Hughes M, Mellors J et al. Efficacy of ART with NVP_TDF/FTC
vs LPV/r_TDF/FTC among antiretroviral-naive women in Africa: OCTANE
Trial 2/ACTG A5208. In: 17th Conference on Retroviruses and
Opportunistic Infections. CROI: San Francisco, CA, 2010. Abstract 153LB.
95. Pulido F, Arribas JR, Delgado R et al. Lopinavir-ritonavir monotherapy
versus lopinavir-ritonavir and two nucleosides for maintenance therapy
of HIV. AIDS 2008; 22: F1–F9.
96. Arribas JR, Horban A, Gerstoft J et al. The MONET trial: darunavir/
ritonavir with or without nucleoside analogues, for patients with
HIV RNA below 50 copies/ml. AIDS 2010; 24: 223–230.
97. Venter WD, Naicker S, Dhai A et al. Uniquely South African: time to
consider offering HIV-positive donor kidneys to HIV-infected renal
failure patients? SAfrMedJ2008; 98: 182–183.
98. Muller E, Kahn D, Mendelson M. Renal transplantation between
HIV-positive donors and recipients. N Engl J Med 2010; 362:
2336–2337.
99. Cofan F, Trullas JC, Cervera C et al. Are HIV-infected donors suitable
for renal transplantation? Transplantation 2011; 91: In press.
DOI: 10.1097/TP.0b013e318206fa5d.
100. Ciuffreda D, Pantaleo G, Pascual M. Effects of immunosuppressive drugs
on HIV infection: implications for solid-organ transplantation. Transpl Int
2007; 20: 649–658.
101. Streblow DN, Kitabwalla M, Malkovsky M et al. Cyclophilin a modulates
processing of human immunodeficiency virus type 1 p55Gag:
mechanism for antiviral effects of cyclosporin A. Virology 1998; 245:
197–202.
102. Chapuis AG, Paolo Rizzardi G, D’Agostino C et al. Effects of
mycophenolic acid on human immunodeficiency virus infection in vitro
and in vivo. Nat Med 2000; 6: 762–768.
103. Hossain MM, Coull JJ, Drusano GL et al. Dose proportional inhibition of
HIV-1 replication by mycophenolic acid and synergistic inhibition in
combination with abacavir, didanosine, and tenofovir. Antiviral Res 2002;
55: 41–52.
104. Sankatsing SU, Hoggard PG, Huitema AD et al. Effect of mycophenolate
mofetil on the pharmacokinetics of antiretroviral drugs and on
intracellular nucleoside triphosphate pools. Clin Pharmacokinet 2004;
43: 823–832.
105. Gilliam BL, Heredia A, Devico A et al. Rapamycin reduces CCR5 mRNA
levels in macaques: potential applications in HIV-1 prevention and
treatment. AIDS 2007; 21: 2108–2110.
106. 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.
107. Bosch RJ, Pollard RB, Landay A et al. Continuing or adding IL-2 in
patients treated with antiretroviral therapy (ACTG Protocol A5051, a
rollover trial of ACTG Protocol A328). AIDS Res Ther 2010; 7: 30.
108. Carter JT, Melcher ML, Carlson LL et al. Thymoglobulin-associated CD4+
T-cell depletion and infection risk in HIV-infected renal transplant
recipients. Am J Transplant 2006; 6: 753–760.
109. Moscoso-Solorzano GT, Baltar JM, Seco M et al. Single dose of rituximab
plus plasmapheresis in an HIV patient with acute humoral kidney
transplant rejection: a case report. Transplant Proc 2007; 39: 3460–3462.
110. Brinkman K, Huysmans F, Burger DM. Pharmacokinetic interaction
between saquinavir and cyclosporine. Ann Intern Med 1998; 129:
914–915.
111. Barrail-Tran A, Furlan V, Blouin P et al. Effect of coadministered boosted
protease inhibitors regimen on tacrolimus blood concentration in 3 kidney
transplanted HIV-infected patients. 8th International Workshop on
Clinical Pharmacology of HIV Therapy, Budapest, Hungary, 2007.
Abstract 58.
112. Jain AK, Venkataramanan R, Shapiro R et al. The interaction between
antiretroviral agents and tacrolimus in liver and kidney transplant
patients. Liver Transpl 2002; 8: 841–845.
113. Tseng A, Nguyen ME, Cardella C et al. Probable interaction between
efavirenz and cylcosporine. AIDS 2002; 16: 505–506.
114. Frassetto LA, Browne M, Cheng A et al. Immunosuppressant
pharmacokinetics and dosing modifications in HIV-1 infected liver and
kidney transplant recipients. Am J Transplant 2007; 7: 2816–2820.
115. Teicher E, Vittecoq D, Taubert AM et al. Liver transplantation in
HIV-coinfected patients treated with enfuvirtide. 13th Conference on
Retroviruses and Opportunistic Infections, Denver, CO, USA, 2006.
Abstract 874.
116. Moreno A, Ba
´
rcena R, Quereda C et al. Safe use of raltegravir and
sirolimus in an HIV-infected patient with renal impairment after
orthotopic liver transplantation. AIDS 2008; 22: 547–548.
117. Guaraldi G, Cocchi S, Codeluppi M et al. Pharmacokinetic interaction
between amprenavir/ritonavir and fosamprenavir on cyclosporine in
two patients with human immunodeficiency virus infection undergoing
orthotopic liver transplantation. Transplant Proc 2006; 38: 1138–1140.
118. Margolis DM, Kewn S, Coull JJ et al. The addition of mycophenolate
mofetil to antiretroviral therapy including abacavir is associated
with depletion of intracellular deoxyguanosine triphosphate and a
decrease in plasma HIV-1 RNA. J Acquir Immune Defic Syndr 2002; 31:
45–49.
119. Regazzi M, Villani P, Lapoce R et al. Pharmacokinetic evaluation of
antiretroviral and immunosuppressive therapy in acute HIV infection
following solid-organ transplantation. 9th International Workshop on
Clinical Pharmacology of HIV Therapy, New Orleans, LA, 2008. Abstract
P53.
120. Neff GW, Bonham A, Tzakis AG et al. Orthotopic liver transplantation in
patients with human immunodeficiency virus and end-stage liver
disease. Liver Transpl 2003; 9: 239–247.
121. Schonder KS, Schullo MA, Okusanya O. Tacrolimus and lopinavir/
ritonavir interaction in liver transplantation. Ann Pharmacother 2003; 37:
1793–1796.
122. Sheikh AM, Wolf DC, Lebovics E et al. Concomitant human
immunodeficiency virus protease inhibitor therapy markedly reduces
tacrolimus metabolism and increases blood levels. Transplantation 1999;
68: 307–309.
123. Vogel M, Voigt E, Michaelis HC et al. Management of drug-to-drug
interactions between cyclosporine A and the protease-inhibitor
lopinavir/ritonavir in liver-transplanted HIV-infected patients. Liver
Transpl 2004; 10: 939–944.
Kidney International (2011) 79 , 825–842 841
JC Trullas et al.: Renal transplantation and HIV review
Page 17
124. Tuset M, Miro JM, Codina C et al. eds. Antiretroviral agents drug-drug
interactions website (Spanish). Available at: http://
www.interaccioneshiv.com/ (accessed 10 March 2010).
125. Back D, Gibbons S. The University of Liverpool HIV drug interactions
website: http://www.hiv-druginteractions.org (accessed 10 March 2010).
126. Certican (everolimus) product information. Novartis Pharma Stein AG:
Switzerland. Available at: http://www.health.gov.il/units/pharmacy/
trufot/alonim/2256.pdf (accessed 10 March 2010).
127. Prograf (tacrolimus) prescribing information. Astellas Pharma US.
Available at: http://www.astellas.us/docs/prograf.pdf [accessed 4
January 2011].
128. Rapamune (sirolimus) product information. European Medicines Agency
(EMEA). EPARs for authorised medicinal products for human use.
Available at: http://www.emea.europa.eu/htms/human/epar/a.htm
(accessed 10 March 2010).
129. Sandimmune (cyclosporine) product information. Novartis
Pharmaceuticals Corporation: East Hanover, New Jersey, 2007
Available at: http://www.pharma.us.novartis.com/product/pi/pdf/
sandimmune.pdf (accessed 10 March 2010).
130. Abbott KC, Lentine KL, Bucci JR et al. The impact of transplantation with
deceased donor hepatitis c-positive kidneys on survival in wait-listed
long-term dialysis patients. Am J Transplant 2004; 4: 2032–2037.
131. Mahmoud IM, Elhabashi AF, Elsawy E et al. The impact of hepatitis C
virus viremia on renal graft and patient survival: a 9-year prospective
study. Am J Kidney Dis 2004; 43: 131–139.
132. Teta D, Luscher BL, Gonvers JJ et al. Pegylated interferon for the
treatment of hepatitis C virus in haemodialysis patients. Nephrol Dial
Transplant 2005; 20: 991–993.
133. Fontaine H, Vallet-Pichard A, Equi-Andrade C et al. Histopathologic
efficacy of ribavirin monotherapy in kidney allograft recipients with
chronic hepatitis C. Transplantation 2004; 78: 853–857.
134. Kamar N, Izopet J, Alric L et al. Lack of evidence for ribavirin
monotherapy efficacy on liver fibrosis in hepatitis C virus positive
renal transplant patients. Transplantation 2005; 79: 1770–1771.
135. Vanrenterghem YF, Claes K, Montagnino G et al. Risk factors for
cardiovascular events after successful renal transplantation.
Transplantation 2008; 85: 209–216.
136. Fine DM, Perazella MA, Lucas GM et al. Renal disease in patients with HIV
infection: epidemiology, pathogenesis and management. Drugs 2008;
68: 963–980.
137. Roland ME, Lo B, Braff J et al. Key clinical, ethical, and policy issues
in the evaluation of the safety and effectiveness of solid organ
transplantation in HIV-infected patients. Arch Intern Med 2003; 163:
1773–1778.
138. Miro JM, Ricart MJ, Trullas JC et al. Pancreas-kidney transplantation in an
HIV-infected patient treated with raltegravir: case report and literature
review. Transplant Proc 2010; 42: 3887–3891.
139. Genzini T, Noujaim HM, Mota LT et al. Simultaneous pancreas-kidney
transplantation in a human immunodeficiency virus-positive recipient: a
case report. Transplant Proc 2010;
42: 591–593.
842 Kidney International (2011) 79 , 825–842
review JC Trullas et al.: Renal transplantation and HIV
Page 18

Similar publications