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1
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Zarinsefat A, Dobi D, Kelly YM, Szabo G, Henrich T, Laszik ZG, Stock PG. An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis. Transplantation 2025; 109:153-160. [PMID: 38867347 DOI: 10.1097/tp.0000000000005096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2024]
Abstract
BACKGROUND Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients. METHODS An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA). RESULTS DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV- cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors. CONCLUSIONS Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.
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Affiliation(s)
- Arya Zarinsefat
- Department of Surgery, University of California, San Francisco, CA
| | - Dejan Dobi
- Department of Pathology, University of California, San Francisco, CA
| | - Yvonne M Kelly
- Department of Surgery, University of California, San Francisco, CA
| | - Gyula Szabo
- Department of Pathology, University of California, San Francisco, CA
| | - Timothy Henrich
- Department of Medicine, University of California, San Francisco, CA
| | - Zoltan G Laszik
- Department of Pathology, University of California, San Francisco, CA
| | - Peter G Stock
- Department of Surgery, University of California, San Francisco, CA
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Wearne N, Botha F, Manning K, Price B, Barday Z, Post FA, Freercks R, Bertels L, Mtingi-Nkonzombi L, Muller E. Clinical and Histopathological Findings in HIV-positive to HIV-positive Kidney Transplant Recipients. Transplantation 2024:00007890-990000000-00938. [PMID: 39590920 DOI: 10.1097/tp.0000000000005271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2024]
Abstract
BACKGROUND The spectrum of histological findings in transplanted kidneys from HIV-positive donors to HIV-positive recipients is relatively unexplored. This study describes the type and timing of histological diagnoses observed in this unique cohort. METHODS Adequate biopsies were analyzed at implantation and posttransplant between September 2008 and May 2022. Histological disease spectrum, distributions over time, and relevant clinical characteristics and management were reported for both for-cause and protocol biopsies. RESULTS Twenty-four implantation biopsies from 31 deceased donors and 179 allograft biopsies (100 for-cause, 79 protocol) from 50 recipients were analyzed. Most rejection episodes occurred in the first year posttransplant. Eighteen recipients (36%) had at least 1 episode of biopsy-confirmed acute/chronic T cell-mediated rejection (TCMR) or active antibody-mediated rejection (AMR). Protocol biopsies showed no active AMR or acute/chronic TCMR. However, 9 of 79 biopsies identified borderline/suspicious TCMR. Common nonrejection diagnoses were interstitial fibrosis and tubular atrophy, ascending pyelonephritis, and calcineurin inhibitor toxicity. Classic and suspected HIV-associated nephropathy (HIVAN) were identified in 3 and 6 patients, respectively. Protocol biopsies diagnosed 1 case of classic HIVAN and 6 cases of suspected HIVAN. AMR most adversely affected kidney function and significantly contributed to graft failure. CONCLUSIONS The histological findings in this cohort of HIV-positive kidney transplant recipients who received grafts from unmatched HIV-positive donors revealed a spectrum of abnormalities. Protocol biopsies added to surveillance on borderline rejection and assisted in the recognition of HIVAN. Confirmed rejection occurred in 18 recipients (36%). Understanding the factors contributing to this may assist in the optimization of immunosuppressive protocols in the future.
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Affiliation(s)
- Nicola Wearne
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Francois Botha
- Pathcare Laboratories, George, South Africa
- Division of Anatomical Pathology, National Health Laboratory Service/University of Cape Town, Faculty of Health Sciences, Groote Schuur Hospital, Cape Town, South Africa
| | - Kathryn Manning
- Department of Surgery, University of Cape Town, Faculty of Health Sciences, Groote Schuur Hospital, Cape Town, South Africa
| | - Brendon Price
- Division of Anatomical Pathology, National Health Laboratory Service/University of Cape Town, Faculty of Health Sciences, Groote Schuur Hospital, Cape Town, South Africa
| | - Zunaid Barday
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Frank A Post
- Division/HIV Medicine and Infectious Diseases, King's College Hospital NHS Foundation Trust, London, United Kingdom
- Division/HIV Medicine and Infectious Diseases, King's College London, London, United Kingdom
| | - Robert Freercks
- Department of Medicine, Nelson Mandela University, Livingstone Hospital, Gqeberha, South Africa
| | - Laurie Bertels
- Department of Surgery, University of Cape Town, Faculty of Health Sciences, Groote Schuur Hospital, Cape Town, South Africa
| | | | - Elmi Muller
- Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Durand CM, Massie A, Florman S, Liang T, Rana MM, Friedman-Moraco R, Gilbert A, Stock P, Mehta SA, Mehta S, Stosor V, Pereira MR, Morris MI, Hand J, Aslam S, Malinis M, Haidar G, Small CB, Santos CAQ, Schaenman J, Baddley J, Wojciechowski D, Blumberg EA, Ranganna K, Adebiyi O, Elias N, Castillo-Lugo JA, Giorgakis E, Apewokin S, Brown D, Ostrander D, Eby Y, Desai N, Naqvi F, Bagnasco S, Watson N, Brittain E, Odim J, Redd AD, Tobian AA, Segev DL. Safety of Kidney Transplantation from Donors with HIV. N Engl J Med 2024; 391:1390-1401. [PMID: 39413376 PMCID: PMC11606542 DOI: 10.1056/nejmoa2403733] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2024]
Abstract
BACKGROUND Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).
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Affiliation(s)
- Christine M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Allan Massie
- Department of Population Health, NYU Grossman School of Medicine, New York, NY
| | - Sander Florman
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, NY
| | - Tao Liang
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Meenakshi M. Rana
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | | | - Peter Stock
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | | | - Shikha Mehta
- Section of Transplant Nephrology, University of Alabama at Birmingham, Birmingham, AL
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Marcus R. Pereira
- Department of Medicine, Columbia University Irving Medical Center, New York, NY
| | - Michele I. Morris
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL
| | - Jonathan Hand
- Department of Medicine, Ochsner Health, New Orleans, LA
| | - Saima Aslam
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA
| | - Maricar Malinis
- Section of Infectious Diseases, Yale School of Medicine, New Haven, CT
| | - Ghady Haidar
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | | | - Carlos A. Q. Santos
- Division of Infectious Diseases, Rush University Medical Center, Chicago, IL
| | - Joanna Schaenman
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - John Baddley
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | | | - Emily A. Blumberg
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | - Karthik Ranganna
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA
| | | | - Nahel Elias
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Jose A. Castillo-Lugo
- Department of Medicine, Methodist Health System Clinical Research Institute, Dallas, TX
| | - Emmanouil Giorgakis
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Senu Apewokin
- Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Diane Brown
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Darin Ostrander
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Yolanda Eby
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Niraj Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Fizza Naqvi
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Serena Bagnasco
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Natasha Watson
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Erica Brittain
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Jonah Odim
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Andrew D. Redd
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Aaron A.R. Tobian
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- Department of Population Health, NYU Grossman School of Medicine, New York, NY
- NYU Langone Transplant Institute, New York, NY
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Wearne N, Davidson B. HIV-associated kidney disease: the changing spectrum and treatment priorities. Curr Opin Nephrol Hypertens 2024:00041552-990000000-00182. [PMID: 39155827 DOI: 10.1097/mnh.0000000000001018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/20/2024]
Abstract
PURPOSE OF REVIEW This review examines the impact of HIV on kidney disease, which remains significant despite advances in antiretroviral therapy (ART). The review is timely due to the shifting epidemiology of kidney disease in people with HIV (PWH), driven by increased ART access, noncommunicable diseases, and region-specific opportunistic infections like tuberculosis. RECENT FINDINGS The literature highlights a decline in HIV-associated nephropathy (HIVAN) and a rise in tubulointerstitial diseases and noncommunicable diseases among PWH. Studies from the United States and South Africa report decreased HIVAN prevalence and increased rates of tubulointerstitial diseases linked to tenofovir disoproxil fumarate (TDF) toxicity and tuberculosis (TB). Immune complex glomerulonephritis (ICGN) and diabetic kidney disease (DKD) are also prevalent. SUMMARY The findings underscore the need for improved diagnostic tools for opportunistic infections, management of ART-related complications, and strategies to address noncommunicable diseases in PWH. There is a need to centralize care to address all health needs simultaneously. Future research should focus on APOL1-targeted therapies and the role of SGLT2 inhibitors in CKD. Enhanced transplantation outcomes and the development of guidelines for managing DKD in PWH are critical for advancing clinical practice and improving patient outcomes.
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Affiliation(s)
- Nicola Wearne
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, South Africa
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5
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Diana NE, Naicker S. The changing landscape of HIV-associated kidney disease. Nat Rev Nephrol 2024; 20:330-346. [PMID: 38273026 DOI: 10.1038/s41581-023-00801-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2023] [Indexed: 01/27/2024]
Abstract
The HIV epidemic has devastated millions of people globally, with approximately 40 million deaths since its start. The availability of antiretroviral therapy (ART) has transformed the prognosis of millions of individuals infected with HIV such that a diagnosis of HIV infection no longer automatically confers death. However, morbidity and mortality remain substantial among people living with HIV. HIV can directly infect the kidney to cause HIV-associated nephropathy (HIVAN) - a disease characterized by podocyte and tubular damage and associated with an increased risk of kidney failure. The reports of HIVAN occurring primarily in those of African ancestry led to the discovery of its association with APOL1 risk alleles. The advent of ART has led to a substantial decrease in the prevalence of HIVAN; however, reports have emerged of an increase in the prevalence of other kidney pathology, such as focal segmental glomerulosclerosis and pathological conditions associated with co-morbidities of ageing, such as hypertension and diabetes mellitus. Early initiation of ART also results in a longer cumulative exposure to medications, increasing the likelihood of nephrotoxicity. A substantial body of literature supports the use of kidney transplantation in people living with HIV, demonstrating significant survival benefits compared with that of people undergoing chronic dialysis, and similar long-term allograft and patient survival compared with that of HIV-negative kidney transplant recipients.
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Affiliation(s)
- Nina E Diana
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Saraladevi Naicker
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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6
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Chandran S, Stock PG, Roll GR. Expanding Access to Organ Transplant for People Living With HIV: Can Policy Catch Up to Outcomes Data? Transplantation 2024; 108:874-883. [PMID: 37723620 DOI: 10.1097/tp.0000000000004794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Advances in antiretroviral and immunosuppressive regimens have improved outcomes following solid organ transplantation in people living with HIV (PLWH). The HIV Organ Policy and Equity Act was conceived to reduce the discard of HIV-positive organs and improve access to transplant for PLWH. Nevertheless, PLWH continue to experience disproportionately low rates of transplant. This overview examines the hurdles to transplantation in PLWH with end-organ disease, the potential and realized impact of the HIV Organ Policy and Equity Act, and changes that could permit expanded access to organ transplant in this population.
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Affiliation(s)
- Sindhu Chandran
- Department of Medicine, University of California-San Francisco (UCSF), San Francisco, CA
| | - Peter G Stock
- Department of Surgery, University of California-San Francisco (UCSF), San Francisco, CA
| | - Garrett R Roll
- Department of Surgery, University of California-San Francisco (UCSF), San Francisco, CA
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Storm K, Durand CM. Overcoming barriers and stigma: new frontiers in solid organ transplantation for people with HIV. Clin Microbiol Rev 2024; 37:e0011122. [PMID: 38240603 PMCID: PMC10938893 DOI: 10.1128/cmr.00111-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2024] Open
Abstract
There is a growing need for solid organ transplantation (SOT) for people living with human immunodeficiency virus (HIV). With the advent of antiretroviral therapy, people living with HIV are experiencing increased life expectancies and are, therefore, developing more comorbidities, including end-stage organ disease. In cases of advanced organ failure, SOT is often the best therapeutic option to improve quality of life and overall survival. As organ shortages persist, transplantation of organs from donors with HIV to recipients with HIV has become a potential therapeutic option. This article first reviews the current state of organ transplantation from donors without HIV to recipients with HIV (HIV D-/R+) by organ and discusses key lessons learned from these transplant trials, including those about drug-drug interactions, rejection, and opportunistic infections. It then explores transplantation from donors with HIV to recipients with HIV (HIV D+/R+), a new frontier. Finally, it investigates challenges of implementation, including public awareness and regulatory requirements, and explores future directions for SOT in people living with HIV.
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Affiliation(s)
- K. Storm
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - C. M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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8
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Motter JD, Hussain S, Brown DM, Florman S, Rana MM, Friedman-Moraco R, Gilbert AJ, Stock P, Mehta S, Mehta SA, Stosor V, Elias N, Pereira MR, Haidar G, Malinis M, Morris MI, Hand J, Aslam S, Schaenman JM, Baddley J, Small CB, Wojciechowski D, Santos CA, Blumberg EA, Odim J, Apewokin SK, Giorgakis E, Bowring MG, Werbel WA, Desai NM, Tobian AA, Segev DL, Massie AB, Durand CM. Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act. Transplantation 2024; 108:759-767. [PMID: 38012862 PMCID: PMC11037099 DOI: 10.1097/tp.0000000000004857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
BACKGROUND Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.
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Affiliation(s)
| | - Sarah Hussain
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Diane M. Brown
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sander Florman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Meenakshi M. Rana
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | | | - Peter Stock
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Shikha Mehta
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Sapna A. Mehta
- Department of Medicine, NYU Grossman School of Medicine, New York, NY
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Nahel Elias
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Marcus R. Pereira
- Department of Medicine, Columbia University Irving Medical Center, New York, NY
| | - Ghady Haidar
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - Maricar Malinis
- Department of Medicine, Yale School of Medicine, New Haven, CT
| | - Michele I. Morris
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Jonathan Hand
- Department of Medicine, Ochsner Health, New Orleans, LA
| | - Saima Aslam
- Department of Medicine, University of California San Diego, La Jolla, CA
| | - Joanna M. Schaenman
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - John Baddley
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Catherine B. Small
- Department of Medicine/Division of Infectious Diseases, Weill Cornell Medicine, New York, NY
| | | | | | - Emily A. Blumberg
- Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Jonah Odim
- Division of Allergy, Immunology and Transplantation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Senu K. Apewokin
- Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH
| | - Emmanouil Giorgakis
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Mary Grace Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - William A. Werbel
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Niraj M. Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Aaron A.R. Tobian
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- Department of Surgery, NYU Grossman School of Medicine, New York, NY
- Department of Population Health, NYU Grossman School of Medicine, New York, NY
- Scientific Registry of Transplant Recipients, Minneapolis, MN
| | - Allan B. Massie
- Department of Surgery, NYU Grossman School of Medicine, New York, NY
- Department of Population Health, NYU Grossman School of Medicine, New York, NY
| | - Christine M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
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9
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Donohue JK, Chan EG, Clifford S, Ryan JP, Furukawa M, Haidar G, Bertani A, Hage CA, Sanchez PG. Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry. Clin Transplant 2024; 38:e15246. [PMID: 38289885 DOI: 10.1111/ctr.15246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/29/2023] [Accepted: 01/12/2024] [Indexed: 02/01/2024]
Abstract
BACKGROUND Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.
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Affiliation(s)
- Jack K Donohue
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ernest G Chan
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Sarah Clifford
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - John P Ryan
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Masashi Furukawa
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ghady Haidar
- Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alessandro Bertani
- Division of Thoracic Surgery and Lung Transplantation, Thoracic Center, IRCCS ISMETT - UPMC, Palermo, Italy
| | - Chadi A Hage
- Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Pablo G Sanchez
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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10
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McMullen L, Drak D, Basu G, Coates PT, Goodman DJ, Graver A, Isbel N, Lim WH, Luxton G, Sciberras F, Toussaint ND, Wong G, Gracey DM. Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience. Nephrology (Carlton) 2024; 29:34-38. [PMID: 37605476 DOI: 10.1111/nep.14229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/31/2023] [Accepted: 08/04/2023] [Indexed: 08/23/2023]
Abstract
Kidney transplantation in people living with HIV (PLWHIV) is occurring with increasing frequency. Limited international data suggest comparable patient and graft survival in kidney transplant recipients with and without HIV. All PLWHIV aged ≥18 years who received a kidney transplant between 2000 and 2020 were identified by retrospective data initially extracted from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), with additional HIV-specific clinical data extracted from linked local health-care records. Twenty-five PLWHIV and kidney failure received their first kidney transplant in Australia between January 2000 and December 2020. Majority were male (85%), with median age 54 years (interquartile range, IQR 43-57). Focal segmental glomerulosclerosis was the most common primary kidney disease (20%), followed by polycystic kidney disease (16%). 80% of patients underwent induction with basiliximab and none with anti-thymocyte globulin (ATG). Participants were followed for median time of 3.5 years (IQR 2.0-6.5). Acute rejection occurred in 24% of patients. Two patients lost their allografts and three died. Virological escape occurred in 28% of patients, with a maximum viral load of 190 copies/mL. In conclusion, kidney transplantation in PLWHIV in Australia is occurring with increasing frequency. Acute rejection is more common than in Australia's general transplant population, but this does not appear to be associated with higher rates of graft failure or mortality out to four years.
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Affiliation(s)
- Lucy McMullen
- Renal Medicine Unit, Royal Prince Alfred Hospital, Sydney, Australia
- Central Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia
| | - Douglas Drak
- Central Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia
| | - Gopal Basu
- Renal Medicine Unit, The Alfred, Melbourne, Victoria, Australia
- Monash University (Central Clinical School), Melbourne, Victoria, Australia
| | - P Toby Coates
- Central Northern Adelaide Renal and Transplantation Service, Adelaide, South Australia, Australia
- University of Adelaide, Adelaide, South Australia, Australia
| | - David J Goodman
- Department of Nephrology, St Vincent's Hospital, Fitzroy, Australia
| | - Alison Graver
- Kidney Transplant Service, Department of Nephrology, Austin Health, Heidelberg, Australia
| | - Nicole Isbel
- Department of Kidney Medicine, Princess Alexandra Hospital, Brisbane, Australia
- University of Queensland, Brisbane, Queensland, Australia
| | - Wai H Lim
- Medical School, University of Western Australia, Perth, Australia
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia
| | - Grant Luxton
- Department of Nephrology, Prince of Wales Hospital, Sydney, Australia
| | - Frederika Sciberras
- Western Renal Services, Western Sydney Local Health District, Sydney, Australia
| | - Nigel D Toussaint
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
- Department of Medicine (RMH), University of Melbourne, Parkville, Victoria, Australia
| | - Germaine Wong
- Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
| | - David M Gracey
- Renal Medicine Unit, Royal Prince Alfred Hospital, Sydney, Australia
- Central Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia
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11
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Kahler D, Curtis H, Zhao H, Diamond A, Di Carlo A, Karhadkar S. Deciphering the True Immunologic Risk in Renal Transplantation in Patients With HIV. Transplant Proc 2023; 55:2392-2397. [PMID: 37932184 DOI: 10.1016/j.transproceed.2023.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/26/2023] [Accepted: 09/26/2023] [Indexed: 11/08/2023]
Abstract
Since 1995, rates of end-stage renal disease have risen dramatically in patients living with HIV infection. However, given the concern for higher rates of acute rejection in this patient population, the immunologic threat posed by HIV infection is a specter clinicians must continually confront. Living donor transplantation may negate this risk; this study aims to assess the benefit of living donor transplantation in this population and to ascertain the immunologic risk faced by patients who are HIV-infected. The 2021 UNOS database was queried, and all HIV-infected kidney transplant recipients since 1987 were identified. Recipients were stratified based on deceased (DDKT) vs living (LDKT) donor status. Overall survival, allograft survival, acute rejection, panel reactive antibody (PRA) percentage, and crossmatch positivity were compared between groups. One thousand two hundred twenty-six patients underwent DDKT, and 304 patients underwent LDKT. Living donor kidney transplantation demonstrated greater overall survival (P = .045) and graft survival (P < .001). However, no difference in acute rejection was noted between the cohorts, and no difference in overall or graft survival was evident based on PRA percentage. Crossmatch positive status did not negatively affect graft survival. Patients with HIV undergoing LDKT fared better than those undergoing DDKT. Nevertheless, patients at higher immunologic risk-elevated PRA% and crossmatch positivity-did not experience graft loss at a higher rate than patients at lower immunologic risk. These results were valid in both DDKT and LDKT cohorts. These findings suggest that infection with HIV does not overtly increase patients' immunologic risk, and concerns surrounding transplantation in this population may be overestimated.
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Affiliation(s)
- Dylan Kahler
- Department of Surgery, Temple University Hospital, Philadelphia, PA
| | - Houston Curtis
- Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Huaqing Zhao
- Center for Biostatistics and Epidemiology, Department of Biomedical Education and Data Science, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Adam Diamond
- Department of Pharmacy, Temple University Hospital, Philadelphia, PA
| | - Antonio Di Carlo
- Division of Abdominal Organ Transplant Surgery, Department of Surgery, Temple University Hospital, Philadelphia, PA
| | - Sunil Karhadkar
- Division of Abdominal Organ Transplant Surgery, Department of Surgery, Temple University Hospital, Philadelphia, PA.
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12
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Almangour TA, Skersick PT, Corbett A, Rodgers JE, Chang PP, Farel CE. Heart transplantation and human immunodeficiency virus-navigating drug-drug interactions: a case report. AIDS Res Ther 2023; 20:55. [PMID: 37568163 PMCID: PMC10422718 DOI: 10.1186/s12981-023-00551-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/19/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions. CASE PRESENTATION A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient's immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30-35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy. CONCLUSION The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.
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Affiliation(s)
- Thamer A Almangour
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
| | - Preston T Skersick
- Department of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, USA
| | - Amanda Corbett
- Department of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, USA
| | - Jo E Rodgers
- Department of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, USA
| | - Patricia P Chang
- Department of Medicine, Division of Cardiology, University of North Carolina School of Medicine, Chapel Hill, USA
| | - Claire E Farel
- Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, USA
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13
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Fontana L, Swanson KJ, El-Rifai R, Bregman A, Spong R, Kirchner VA, Pruett T, Jackson S, Riad S. Recipient and kidney graft outcomes of deceased donors with human immunodeficiency virus in the United States. Transpl Infect Dis 2023; 25:e14093. [PMID: 37432941 DOI: 10.1111/tid.14093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 05/17/2023] [Accepted: 06/16/2023] [Indexed: 07/13/2023]
Abstract
BACKGROUND The HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long-term outcomes of recipients with HIV by donor HIV testing status. METHODS Using the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV-positive between 1/1/16-12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab-/NAT- (n = 810), Donor Ab+ /NAT- (n = 98), and Donor Ab+/NAT+ (n = 90). We compared recipient and death-censored graft survival (DCGS) by donor HIV testing status using Kaplan-Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1-year outcomes: acute rejection, re-hospitalization, and serum creatinine. RESULTS In Kaplan-Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p = .667; log rank p = .388). DGF occurred more frequently in donors with HIV Ab-/NAT- testing compared with Ab+/NAT- or Ab+/NAT+ testing (38.0% vs. 28.6% vs. 26.7%, p = .028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab-/NAT- testing (p < .001). Acute rejection, re-hospitalization and serum creatinine at 12 months did not differ between the groups. CONCLUSIONS Patient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT- or Ab+/NAT+ testing shortens dialysis time prior to transplant.
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Affiliation(s)
- Lauren Fontana
- Division of Infectious Diseases, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Kurtis J Swanson
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Rasha El-Rifai
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Adam Bregman
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Richard Spong
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Varvara A Kirchner
- Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, California, USA
| | - Timothy Pruett
- Division of Transplant Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Scott Jackson
- Analytics Consulting Services, MHealth Fairview, Minneapolis, Minnesota, USA
| | - Samy Riad
- Division of Nephrology and Hypertension, Mayo Clinic Rochester, Minneapolis, Minnesota, USA
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14
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Shelton BA, Becker DJ, MacLennan PA, Sen B, Budhwani H, Locke JE. Racial Disparities in Access to the Kidney Transplant Waitlist Among People with Human Immunodeficiency Virus. AIDS Patient Care STDS 2023; 37:394-402. [PMID: 37566535 PMCID: PMC10457613 DOI: 10.1089/apc.2023.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2023] Open
Abstract
The epidemiology of human immunodeficiency virus (HIV) has shifted such that Black individuals disproportionately represent incident HIV diagnoses. While risk of end-stage kidney disease (ESKD) among people with HIV (PWH) has declined with effective antiretroviral therapies, a substantial racial disparity in ESKD burden exists with the greatest prevalence among Black PWH. Disparities in waitlisting for kidney transplantation, the optimal treatment for ESKD, exist for both PWH and Black individuals without HIV, but it is unknown whether these characteristics together exacerbate such disparities. Six hundred two thousand six ESKD patients were identified from the United States Renal Data System (January 1, 2007 to December 31, 2017), and HIV-status was determined through Medicare claims. Cox proportional hazards regression was used to determine waitlisting rates. Multiplicative interaction terms between HIV-status and race were examined. The 6250 PWH were significantly younger, more commonly Black, and less commonly female than those without HIV. HIV-status and race were independently associated with 50% and 12% lower likelihood of waitlisting, respectively [adjusted hazard ratio (aHR): 0.50, 95% confidence interval (CI): 0.36-0.69, p < 0.001; aHR: 0.88, 95% CI: 0.87-0.90, p < 0.001]. There was also a significant interaction present between HIV-status and Black race (aHR: 0.80, 95% CI: 0.66-0.98, p < 0.001) such that, while HIV-status and Black race were independently associated with decreased waitlisting, the interaction of Black race and HIV-status exacerbated those disparities. While limited by lack of HIV-specific data that may impact inferences with respect to race, additional studies are urgently needed to understand the interplay between HIV risk factors, HIV-stigma, and racism, and how intersectionality may exacerbate disparities in transplantation among PWH.
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Affiliation(s)
- Brittany A. Shelton
- Department of Public Health, University of Tennessee Knoxville, Knoxville, Tennessee, USA
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Ryals School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - David J. Becker
- Ryals School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Paul A. MacLennan
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Bisakha Sen
- Ryals School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Henna Budhwani
- College of Nursing, Florida State University, Tallahassee, Florida, USA
| | - Jayme E. Locke
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
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15
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Lam C, Landry S, Moussa G, Sakr D, Varinot G, Mousseau K, Martel D, Frenette AJ, Ambaraghassi G, Rouleau D, Cantarovich M, Klein MB, Sheehan NL, Lemire B. Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review. Transplant Direct 2023; 9:e1441. [PMID: 36733439 PMCID: PMC9886517 DOI: 10.1097/txd.0000000000001441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 12/01/2022] [Accepted: 12/03/2022] [Indexed: 01/28/2023] Open
Abstract
The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.
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Affiliation(s)
- Cindy Lam
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Sébastien Landry
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Ghina Moussa
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Dania Sakr
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Gabriel Varinot
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Katherine Mousseau
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
| | - Dominic Martel
- Département de pharmacie, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
- Centre de recherche du CHUM, Montréal, QC, Canada
- Unité hospitalière de recherche, d’enseignement et de soins sur le sida, CHUM, Montréal, QC, Canada
| | - Anne Julie Frenette
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Département de pharmacie, Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada
| | - Georges Ambaraghassi
- Service de microbiologie, Département de médecine de laboratoire, CHUM, Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada
| | - Danielle Rouleau
- Centre de recherche du CHUM, Montréal, QC, Canada
- Unité hospitalière de recherche, d’enseignement et de soins sur le sida, CHUM, Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada
| | | | - Marina B. Klein
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
- Division of Infectious Diseases, Department of Medicine, MUHC, Montréal, QC, Canada
| | - Nancy L. Sheehan
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
| | - Benoît Lemire
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
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16
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Donor derived infections in kidney transplant. Dis Mon 2022; 68:101330. [PMID: 35221018 DOI: 10.1016/j.disamonth.2022.101330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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17
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Malashenko AA, Tsyplina EY, Krasnov AO, Anishchenko VV, Krasnov OA. THE CURRENT STATE OF THE PROBLEM IN ORGAN TRANSPLANTATION IN HIV-INFECTED PATIENTS ABROAD AND IN THE RUSSIAN FEDERATION. SURGICAL PRACTICE 2022. [DOI: 10.38181/2223-2427-2022-3-42-48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The work is based on a retrospective analysis of literature data covering tactical approaches, indications and contraindications, treatment results in patients with HIV infection who underwent organ transplantation. The analysis of the most up-to-date publications on organ transplantation in HIV-infected patients in the Russian Federation and abroad has been carried out. The criteria under which the transplantation of an HIV-infected patient is most favorable are noted. Cases of transplantation with subsequent results are described: donor (HIV-) – recipient (HIV+), donor (HIV+) – RECIPIENT (HIV+) and donor (HIV+) – RECIPIENT (HIV-). The main purpose of the review is to analyze modern foreign and domestic literature on the issue of tactical approaches to organ transplantation in HIV-infected patients. It has been established that different countries have different approaches to organ transplantation in HIV-infected patients.
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Affiliation(s)
- A. A. Malashenko
- Federal state Institution Medical and Sanitary Unit No. 42 of the Federal Penitentiary Service of Russia, branch «Hospital No. 1»
| | - E. Yu. Tsyplina
- Federal State Budgetary Educational Institution of Higher Education «Siberian State Medical University»
| | - A. O. Krasnov
- State Autonomous Health Institution "Kuzbass Clinical Emergency Hospital named after M. A. Podgorbunsky
| | - V. V. Anishchenko
- Federal State Budgetary Educational Institution of Higher Education «Novosibirsk State Medical University», Department of Surgery, Faculty of Advanced Training and Professional Retraining of Doctors; Avicena Medical Center JSC, Mother and Child Group of companies
| | - O. A. Krasnov
- Federal Budgetary Educational Institution of Higher Education Kemerovo State Medical University; Department of General, Faculty Surgery and Urology, I. A. Kolpinsky Clinical Consulting and Diagnostic Center, Polyclinic No. 1
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18
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Russo FP, Viganò M, Stock P, Ferrarese A, Pugliese N, Burra P, Aghemo A. HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist. J Hepatol 2022; 77:503-515. [PMID: 35398460 DOI: 10.1016/j.jhep.2022.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 02/08/2022] [Accepted: 03/02/2022] [Indexed: 12/04/2022]
Abstract
Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.
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Affiliation(s)
- Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy
| | - Mauro Viganò
- Division of Hepatology, San Giuseppe Hospital, MultiMedica IRCCS, Milan, Italy
| | - Peter Stock
- Department of Surgery, University of California at San Francisco, San Francisco, California, USA
| | - Alberto Ferrarese
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
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19
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Papp KA, Beecker J, Cooper C, Kirchhof MG, Pozniak AL, Rockstroh JK, Dutz JP, Gooderham MJ, Gniadecki R, Hong CH, Lynde CW, Maari C, Poulin Y, Vender RB, Walmsley SL. Use of Systemic Therapies for Treatment of Psoriasis in People Living with Controlled HIV: Inference-Based Guidance from a Multidisciplinary Expert Panel. Dermatol Ther (Heidelb) 2022; 12:1073-1089. [PMID: 35445963 PMCID: PMC9110627 DOI: 10.1007/s13555-022-00722-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 03/30/2022] [Indexed: 11/28/2022] Open
Abstract
Background People living with human immunodeficiency virus (PLHIV) have a similar prevalence of psoriasis as the general population, though incidence and severity correlate with HIV viral load. Adequately treating HIV early renders the infection a chronic medical condition and allows PLHIV with a suppressed viral load (PLHIV-s) to live normal lives. Despite this, safety concerns and a lack of high-level data have hindered the use of systemic psoriasis therapies in PLHIV-s. Objectives We aim to provide a structured framework that supports healthcare professionals and patients discussing the risks and benefits of systemic psoriasis therapy in PLHIV-s. Our goal was to address the primary question, are responses to systemic therapies for the treatment of psoriasis in PLHIV-s similar to those in the non-HIV population? Methods We implemented an inference-based approach relying on indirect evidence when direct clinical trial data were absent. In this instance, we reviewed indirect evidence supporting inferences on the status of immune function in PLHIV. Recommendations on systemic treatment for psoriasis in PLHIV were derived using an inferential heuristic. Results We identified seven indirect indicators of immune function informed by largely independent bodies of evidence: (1) functional assays, (2) vaccine response, (3) life expectancy, (4) psoriasis manifestations, (5) rate of infections, (6) rate of malignancies, and (7) organ transplant outcomes. Conclusions Drug-related benefits and risks when treating a patient with systemic psoriasis therapies are similar for non-HIV patients and PLHIV with a suppressed viral load and normalized CD4 counts. Prior to initiating psoriasis treatment in PLHIV, HIV replication should be addressed by an HIV specialist. Exercise additional caution for patients with a suppressed viral load and discordant CD4 responses on antiretroviral therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00722-0. People living with human immunodeficiency virus (PLHIV) develop psoriasis as often as everyone else. We asked: what are effective and safe treatments when PLHIV need systemic therapy (pills or injections) for their psoriasis? HIV infection attacks the immune system. When HIV is not treated, the immune system declines. A less effective immune system makes it harder for the body to fight infections and certain cancers. Psoriasis is a skin condition caused by overactive immune cells. Effective psoriasis treatments reduce immune-cell activity. There are some concerns that treatments for psoriasis may not work and could worsen infections or cancers. To answer the question, we gathered 11 dermatologists and 4 HIV specialists. We reviewed the international scientific literature on PLHIV and psoriasis. The absence of direct evidence and volume of information to review made the process challenging. The end results were worthwhile. We concluded that people who are diagnosed early and take antiretroviral therapy to control their HIV infection (PLHIV-c) can live long, healthy lives. Accordingly, we determined that PLHIV-c can likely expect the same safety and efficacy for systemic psoriasis treatments as the general population. Treatment decisions should be made on a case-by-case basis through consultation with the patient and treating physician(s). Pillars of modern medicine are evidence-based care and collaborative decision-making. Too often, neither care provider nor patient are adequately informed. We have tried to fill one information gap for PLHIV and psoriasis. This process may help answer questions in other disease populations where direct evidence is scarce or absent.
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Affiliation(s)
- Kim A Papp
- Probity Medical Research Inc., Waterloo, ON, Canada. .,K Papp Clinical Research, Waterloo, ON, Canada.
| | - Jennifer Beecker
- Probity Medical Research Inc., Waterloo, ON, Canada.,University of Ottawa, Ottawa, ON, Canada.,Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada.,Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Curtis Cooper
- University of Ottawa, Ottawa, ON, Canada.,Ottawa Hospital Research Institute, Ottawa, ON, Canada.,The Ottawa Hospital and Regional Hepatitis Program, Ottawa, ON, Canada
| | - Mark G Kirchhof
- University of Ottawa, Ottawa, ON, Canada.,Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada
| | - Anton L Pozniak
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | - Jan P Dutz
- Skin Care Center, Vancouver, BC, Canada.,Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.,BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Melinda J Gooderham
- Probity Medical Research Inc., Waterloo, ON, Canada.,SKiN Centre for Dermatology, Peterborough, ON, Canada
| | - Robert Gniadecki
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Chih-Ho Hong
- Probity Medical Research Inc., Waterloo, ON, Canada.,Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.,Dr. Chih-Ho Hong Medical Inc., Surrey, BC, Canada
| | - Charles W Lynde
- Probity Medical Research Inc., Waterloo, ON, Canada.,Lynde Institute for Dermatology, Markham, ON, Canada
| | | | - Yves Poulin
- Centre de Recherche Dermatologique du Québec Métropolitain, Quebec, QC, Canada
| | - Ronald B Vender
- Dermatrials Research Inc., Hamilton, ON, Canada.,Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Sharon L Walmsley
- Toronto General Hospital Research Institute, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada.,Department of Medicine, University Health Network, Toronto, ON, Canada
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20
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Zarinsefat A, Gulati A, Shui A, Braun H, Rogers R, Hirose R, Ascher N, Stock P. Long-term Outcomes Following Kidney and Liver Transplant in Recipients With HIV. JAMA Surg 2022; 157:240-247. [PMID: 34985513 PMCID: PMC8733865 DOI: 10.1001/jamasurg.2021.6798] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Importance Kidney transplant (KT) and liver transplant (LT) in HIV-positive patients have become more widely adopted. Data looking at long-term outcomes of patient and graft survival are lacking. Objective To compare the long-term outcomes of KT and LT in HIV-positive recipients with matched HIV-negative recipients. Design, Setting, and Participants Retrospective, single-center, cohort, study using data from 2000 to 2019. Patients were observed until death, or graft failure requiring retransplant. All HIV-positive patients who underwent KT and/or LT between 2000 and 2019 were included. Propensity matching was performed to the corresponding HIV-negative cohort, which was obtained from the University of California, San Francisco's transplant recipient registry. The data were analyzed from 2020 to 2021. Exposures HIV infection. Main Outcomes and Measures Patient and graft survival for KT and patient survival for LT. Incidence of acute rejection and its association with KT graft survival. Results For KT, 655 HIV-negative recipients (mean [SD] age, 52.3 [13.6] years; 450 [68.7%] were men) and 119 HIV-positive recipients (mean [SD] age, 51.7 [9.4] years; 86 [72.3%] were men) were included. Patient survival was 79.6% (95% CI, 73.6%-86.1%) and 53.6% (95% CI, 38.9%-74.0%) at 15 years posttransplant, respectively. Graft survival was 57.0% (95% CI, 47.8%-68.0%) and 75.0% (95% CI, 65.3%-86.2%) at 15 years posttransplant, respectively. Diagnosis of HIV was not associated with worse graft survival (hazard ratio, 1.09; 95% CI, 0.61-1.97; P = .77). For LT, 80 HIV-positive recipients (mean [SD] age, 52.6 [8.2] years; 53 [66.3%] were men) and 440 HIV-negative recipients (mean [SD] age, 54.6 [12.8] years; 291 [66.1%] were men) were included. Patient survival was 75.7% (95% CI, 71.8%-79.8%) for HIV-negative LT recipients and 70.0% (95% CI, 60.6%-80.8%) for HIV-positive LT recipients at 15 years posttransplant. Diagnosis of HIV was not a statistically significant predictor of patient survival (hazard ratio, 1.36; 95% CI, 0.83-2.24; P = .22). In KT, HIV-positive patients with at least 1 episode of acute rejection had a graft survival of 52.8% (95% CI, 38.4%-72.5%; P < .001) at 15 years posttransplant, compared with 91.8% in those without AR. Conclusions and Relevance In this single-center cohort study, KT and LT in HIV-positive patients had comparable long-term outcomes with those in matched HIV-negative patients. The high incidence of acute rejection was associated with reduced graft survival. The findings support providing transplant to HIV-positive patients, which may be an appropriate use of transplant resources and provides equitable access for HIV-positive patients.
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Affiliation(s)
- Arya Zarinsefat
- Department of Surgery, University of California, San Francisco
| | - Arushi Gulati
- School of Medicine, University of California, San Francisco
| | - Amy Shui
- Department of Epidemiology and Biostatistics, University of California, San Francisco
| | - Hillary Braun
- Department of Surgery, University of California, San Francisco
| | - Rodney Rogers
- Department of Surgery, University of California, San Francisco
| | - Ryutaro Hirose
- Department of Surgery, University of California, San Francisco
| | - Nancy Ascher
- Department of Surgery, University of California, San Francisco
| | - Peter Stock
- Department of Surgery, University of California, San Francisco
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21
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Adekunle RO, Zhang R, Wang Z, Patzer RE, Mehta AK. Early steps to kidney transplantation among persons with HIV and end-stage renal disease in ESRD network 6. Transpl Infect Dis 2022; 24:e13767. [PMID: 34813136 PMCID: PMC8825692 DOI: 10.1111/tid.13767] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 10/18/2021] [Accepted: 11/10/2021] [Indexed: 02/03/2023]
Abstract
INTRODUCTION End-stage renal disease is a significant cause of morbidity and mortality in persons with HIV (PWH). Limited data exist on access to kidney transplantation for this population. METHODS A dataset inclusive of incident dialysis patients between 2012 and 2016 with follow-up through December 2017 that identifies PWH and the general dialysis population of Network 6 (Georgia, North Carolina, South Carolina) was created through merging the United States Renal Data System with the southeastern early transplant access registry. Early steps to kidney transplantation and patient and dialysis facility-level characteristics that serve as barriers to transplantation were described. RESULTS Twenty-three thousand four hundred fourteen patients were identified; 469 were PWH. Compared to non-HIV individuals, PWH were younger (49 vs. 58 years, p < 0.001), predominantly Black (87% vs. 56% p < 0.001) and male (72% vs. 56% p < 0.001). PWH were less likely to be referred to kidney transplant within 1 year of starting dialysis (36% vs. 41% p < 0.001) and waitlisted within 1 year of evaluation-start (14% vs. 30%, p = 0.05). PWH (vs. non-PWH) waited longer for referral, evaluation-start, and waitlisting and in multivariable analysis; HIV positivity was associated with a lower probability of referral (hazard ratios [HR]: 0.70; 95% confidence intervals [CIs]: 0.62-0.80), evaluation (HR 0.66; 95% CI: 0.55-0.80), and waitlisting (HR 0.29; 95% CI: 0.20-0.41). CONCLUSIONS Targeted interventions are needed to improve access to kidney transplants, particularly in waitlisting, for PWH.
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Affiliation(s)
- Ruth O Adekunle
- Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Rebecca Zhang
- Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | - Zhengsheng Wang
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Rachel E Patzer
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Aneesh K Mehta
- Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia Emory Transplant Center, Atlanta, Georgia,Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
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22
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Klitenic SB, Levan ML, Van Pilsum Rasmussen SE, Durand CM. Science Over Stigma: Lessons and Future Direction of HIV-to-HIV Transplantation. CURRENT TRANSPLANTATION REPORTS 2021; 8:314-323. [PMID: 34812403 PMCID: PMC8600909 DOI: 10.1007/s40472-021-00345-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/06/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW The HIV Organ Policy Equity (HOPE) Act permits transplantation from donors-with-HIV to recipients-with-HIV (HIV D + /R +). We assess HOPE implementation, summarizing progress and challenges at clinical, legislative, and community levels. RECENT FINDINGS As of July 2021, there have been 300 kidney and 87 liver transplants within HOPE research studies in the USA. Early HIV D + /R + kidney transplant outcomes show excellent patient survival (100%) and graft survival (92%). The number of HOPE donors continues to grow annually but remains lower than projections. State-level policy restrictions are identified in 34 states; however, these do not seem to have impacted practice; 16 states have passed new legislation to facilitate HIV D + /R + transplantation. Stigma related to HIV and low donor registration rates pose additional barriers. SUMMARY Early outcomes of HOPE Act transplants are encouraging. Progress to reach full implementation and realize the full benefit of this innovation is ongoing.
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Affiliation(s)
- Samantha B. Klitenic
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD USA
| | - Macey L. Levan
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD USA
| | | | - Christine M. Durand
- Department of Medicine and Oncology, Johns Hopkins University School of Medicine, 725 North Wolfe Street/PCTB 228, Baltimore, MD 21205 USA
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA
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23
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Pereira MR, Dube GK, Tatem L, Burack D, Crew RJ, Cohen DJ, Ratner LE. HIV transmission through living donor kidney transplant: An 11-year follow-up on the recipient and donor. Transpl Infect Dis 2021; 23:e13691. [PMID: 34265862 DOI: 10.1111/tid.13691] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/09/2021] [Accepted: 07/05/2021] [Indexed: 11/29/2022]
Abstract
HIV transmission via solid organ transplant is a rare but serious complication. Here, we describe long-term outcomes in a case of living donor-derived transmission of HIV in a kidney transplant recipient. After 11 years since transplant surgery, the donor shows no evidence of abnormal renal function, while the recipient continues to have a functioning graft. HIV is well controlled in both individuals. This single case report highlights the possibility of acceptable long-term outcomes in living kidney donors with HIV as well as in donor-derived HIV transmission to kidney transplant recipients.
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Affiliation(s)
- Marcus R Pereira
- Division of Infectious Disease, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Geoffrey K Dube
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Luis Tatem
- Division of Infectious Disease, Department of Medicine, SUNY Downstate Health Sciences University, New York, New York, USA
| | - Daniel Burack
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Russell J Crew
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - David J Cohen
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Lloyd E Ratner
- Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA
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24
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Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation 2021; 105:1492-1501. [PMID: 33044431 PMCID: PMC8026768 DOI: 10.1097/tp.0000000000003485] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors. METHODS We aimed to evaluate the effectiveness of transplantation in HIV-positive patients and highlight some of the important issues reported in the literature. We pooled clinical data from different cohorts to show some of the common issues encountered in HIV-positive transplantation. Furthermore, we searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV-positive patients. RESULTS We included data from 19 cohort studies and reported on outcomes of the current HIV-positive transplant programs. We made recommendations based on personal experience as well as the experience reported in the literature regarding rejection, opportunistic infection, and HIV-associated nephropathy. Opportunistic infections and malignancies are not a major problem for this population group. CONCLUSIONS HIV-positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. When utilizing HIV-positive donors, the recurrence of HIV-associated nephropathy in the graft kidney is an issue which can be important. Despite some issues with high rejection rates, HIV-positive patients have similar results to HIV-negative patients posttransplantation.
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Affiliation(s)
- Elmi Muller
- Division of General Surgery, Department of Surgery, University of Cape Town, South Africa
| | | | | | - Kathryn Manning
- Division of General Surgery, Department of Surgery, University of Cape Town, South Africa
| | - Peter Chin-Hong
- Division of Infectious Diseases, Department of Medicine, University of California San Francisco, USA
| | - Peter Stock
- Department of Surgery, University of California San Francisco, USA
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25
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Udomkarnjananun S, Naiyarakseree N, Townamchai N, Surinrat E, Tiankanon K, Banjongjit A, Vanichanan J, Jutivorakool K, Putcharoen O, Suankratay C, Surintrspanont J, Iampenkhae K, Leelahavanichkul A, Wattanatorn S, Apisutimaitri K, Burimsittichai R, Ratchanon S, Nonthasoot B, Sirichindakul B, Praditpornsilpa K, Avihingsanon Y. The first report of kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and literature review: Encouragement for developing countries in Southeast Asia. SAGE Open Med Case Rep 2021; 9:2050313X211024471. [PMID: 34211716 PMCID: PMC8216421 DOI: 10.1177/2050313x211024471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 05/20/2021] [Indexed: 11/17/2022] Open
Abstract
Patients with human immunodeficiency virus infection are at risk of chronic kidney disease and end-stage renal disease. Human immunodeficiency virus infection impedes patients' accessibility to transplantation in Thailand and other developing countries in Southeast Asia, where the burdens of human immunodeficiency virus infection and chronic kidney disease are rapidly increasing. We report the successful kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and provide brief information about the current knowledge of human immunodeficiency virus medicine and transplantation that are needed for conducting kidney transplantations in such patients. Patient selection and evaluation, the choice of antiretroviral therapy, immunosuppressive regimens, and infectious complications are reviewed and discussed. The aim is to encourage kidney transplantation in end-stage renal disease patients with well-controlled human immunodeficiency virus infection, especially in countries where the prevalence of human immunodeficiency virus infection is high and the accessibility to transplantation is still limited.
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Affiliation(s)
- Suwasin Udomkarnjananun
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Renal Immunology and Transplantation Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Nuanjanthip Naiyarakseree
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Natavudh Townamchai
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Renal Immunology and Transplantation Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Ekkapong Surinrat
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kanitha Tiankanon
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Athiphat Banjongjit
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Jakapat Vanichanan
- Division of Infectious Disease, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kamonwan Jutivorakool
- Division of Infectious Disease, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Opass Putcharoen
- Division of Infectious Disease, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Chusana Suankratay
- Division of Infectious Disease, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Jerasit Surintrspanont
- Department of Pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kroonpong Iampenkhae
- Department of Pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Asada Leelahavanichkul
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Salin Wattanatorn
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kirada Apisutimaitri
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Rattanaporn Burimsittichai
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Supoj Ratchanon
- Department of Surgery, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Bunthoon Nonthasoot
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Department of Surgery, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Boonchoo Sirichindakul
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Department of Surgery, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kearkiat Praditpornsilpa
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Yingyos Avihingsanon
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Renal Immunology and Transplantation Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
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26
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Durand CM, Zhang W, Brown DM, Yu S, Desai N, Redd AD, Bagnasco SM, Naqvi FF, Seaman S, Doby BL, Ostrander D, Bowring MG, Eby Y, Fernandez RE, Friedman-Moraco R, Turgeon N, Stock P, Chin-Hong P, Mehta S, Stosor V, Small CB, Gupta G, Mehta SA, Wolfe CR, Husson J, Gilbert A, Cooper M, Adebiyi O, Agarwal A, Muller E, Quinn TC, Odim J, Huprikar S, Florman S, Massie AB, Tobian AAR, Segev DL. A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action. Am J Transplant 2021; 21:1754-1764. [PMID: 32701209 PMCID: PMC8073960 DOI: 10.1111/ajt.16205] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.
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Affiliation(s)
- Christine M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Wanying Zhang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Diane M. Brown
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sile Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Niraj Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Andrew D. Redd
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Serena M. Bagnasco
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Fizza F. Naqvi
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shanti Seaman
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brianna L. Doby
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Darin Ostrander
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mary Grace Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Yolanda Eby
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Reinaldo E. Fernandez
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Rachel Friedman-Moraco
- Department of Medicine, Emory University, Atlanta, Georgia
- Department of Surgery, Emory University, Atlanta, Georgia
| | - Nicole Turgeon
- Department of Surgery, Emory University, Atlanta, Georgia
- Department of Surgery, Dell Medical School, University of Texas, Austin, Texas
| | - Peter Stock
- Department of Medicine, University of California, San Francisco, California
| | - Peter Chin-Hong
- Department of Medicine, University of California, San Francisco, California
| | - Shikha Mehta
- Section of Transplant Nephrology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Valentina Stosor
- Department of Infectious Diseases and Organ Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Catherine B. Small
- Department of Medicine/Division of Infectious Diseases, Weill Cornell Medicine, New York, New York
| | - Gaurav Gupta
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Sapna A. Mehta
- NYU Langone Transplant Institute, New York University Grossman School of Medicine, New York, New York
| | - Cameron R. Wolfe
- Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina
| | - Jennifer Husson
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Alexander Gilbert
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, District of Columbia
| | - Matthew Cooper
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, District of Columbia
| | - Oluwafisayo Adebiyi
- Department of Medicine, Indiana University Health Hospital, Indianapolis, Indiana
| | - Avinash Agarwal
- Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia
| | - Elmi Muller
- Department of Surgery, University of Cape Town, Cape Town, South Africa
| | - Thomas C. Quinn
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Jonah Odim
- Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Shirish Huprikar
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, New York
| | - Sander Florman
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, New York
| | - Allan B. Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Aaron A. R. Tobian
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 2021; 104:S11-S103. [PMID: 32301874 DOI: 10.1097/tp.0000000000003136] [Citation(s) in RCA: 314] [Impact Index Per Article: 78.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.
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Boyarsky BJ, Strauss AT, Segev DL. Transplanting Organs from Donors with HIV or Hepatitis C: The Viral Frontier. World J Surg 2021; 45:3503-3510. [PMID: 33471156 DOI: 10.1007/s00268-020-05924-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2020] [Indexed: 12/21/2022]
Abstract
A wide gap between the increasing demand for organs and the limited supply leads to immeasurable loss of life each year. The organ shortage could be attenuated by donors with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). The transplantation of organs from HIV+ deceased donors into HIV+ individuals (HIV D+ /R+) was initiated in South Africa in 2010; however, this practice was forbidden in the USA until the HIV Organ Policy Equity (HOPE) Act in 2013. HIV D+/R+ transplantation is now practiced in the USA as part of ongoing research studies, helping to reduce waiting times for all patients on the waitlist. The introduction of direct acting antivirals for HCV has revolutionized the utilization of donors with HCV for HCV-uninfected (HCV-) recipients. This is particularly relevant as the HCV donor pool has increased substantially in the context of the rise in deaths related to drug overdose from injection drug use. This article serves to review the current literature on using organs from donors with HIV or HCV.
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Affiliation(s)
- Brian J Boyarsky
- Department of Surgery, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University School of Medicine, 2000 E Monument St, Baltimore, MD, 21205, USA
| | - Alexandra T Strauss
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Dorry L Segev
- Department of Surgery, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University School of Medicine, 2000 E Monument St, Baltimore, MD, 21205, USA. .,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
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29
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Sawinski D, Wong T, Goral S. Current state of kidney transplantation in patients with HIV, hepatitis C, and hepatitis B infection. Clin Transplant 2020; 34:e14048. [PMID: 32700341 DOI: 10.1111/ctr.14048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 07/11/2020] [Accepted: 07/15/2020] [Indexed: 02/06/2023]
Abstract
Human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common chronic viral infections in the end-stage kidney disease (ESKD) patient population that were once considered relative contraindications to kidney transplantation. In this review, we will summarize the current state of kidney transplantation in patients with HIV, HCV, and HBV, which is rapidly evolving. HIV+ patients enjoy excellent outcomes in the modern transplant era and may have new transplant opportunities with the use of HIV+ donors. Direct-acting antivirals for HCV have substantially changed the landscape of care for patients with HCV infection. HBV+ patients now have excellent patient and allograft survival with HBV therapy. Currently, kidney transplantation is a safe and appropriate treatment for the majority of ESKD patients with HIV, HCV, and HBV.
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Affiliation(s)
- Deirdre Sawinski
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Tiffany Wong
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Simin Goral
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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30
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Santeusanio A, Bhansali A, De Boccardo G, Sehgal V, Delaney V, Florman S, Shapiro R. Conversion to belatacept maintenance immunosuppression in HIV-positive kidney transplant recipients. Clin Transplant 2020; 34:e14041. [PMID: 32654239 DOI: 10.1111/ctr.14041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 07/08/2020] [Indexed: 12/22/2022]
Abstract
There are only scattered case reports documenting belatacept use in HIV + kidney transplant recipients. We performed a retrospective review to describe short-term outcomes following conversion to belatacept in a cohort of HIV + patients. Patients were included if they were converted to belatacept between May 2015 and May 2019, had an HIV- donor, and received ≥4 doses of belatacept. All patients were treated with non-depleting induction and triple maintenance immunosuppression. Allograft and HIV-related outcomes were collected from the date of belatacept infusion until May 2020. Ten HIV + kidney transplant recipients were identified, who were converted to belatacept a median of 364 days post-transplant. At last follow-up (median 3.3 years), 8 patients remained on belatacept therapy, and all patients were alive with functioning allografts. Mean estimated glomerular filtration rates (eGFR) improved from 31.6 mL/min at baseline to 42.8 mL/min at 1 year (P = .03). Two patients developed acute rejection, with one necessitating conversion back to tacrolimus. All patients maintained undetectable HIV-1 viral loads at last follow-up. One patient each developed pneumocystis pneumonia and Kaposi sarcoma following conversion, which were responsive to standard medical therapy. In our cohort of stable HIV + kidney transplant recipients, conversion to belatacept was associated with excellent early patient and allograft survival and improved eGFR at 1 year.
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Affiliation(s)
- Andrew Santeusanio
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA.,Department of Pharmacy, Mount Sinai Hospital, New York, NY, USA
| | - Arjun Bhansali
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA
| | - Graciela De Boccardo
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA
| | - Vinita Sehgal
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA
| | - Veronica Delaney
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA
| | - Sander Florman
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA
| | - Ron Shapiro
- Mount Sinai Hospital, Recanati-Miller Transplantation Institute, New York, NY, USA
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31
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Abstract
Individuals with HIV are at increased risk for ESKD. Kidney transplantation is the best treatment for ESKD in the HIV+ population. Despite reduced access to transplantation, patients who are HIV+ have excellent outcomes and clearly benefit from receiving one. Common post-transplant complications and management concerns, including the optimal antiretroviral regimen, immunosuppression protocols, infectious prophylaxis, hepatitis C coinfection, metabolic complications, and malignancy are all discussed.
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Affiliation(s)
- Deirdre Sawinski
- Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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32
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Abstract
: With current antiretroviral therapy, the lifespan of newly diagnosed persons with HIV (PWH) approaches that of uninfected persons. However, metabolic abnormalities related to both the disease and the virus itself, along with comorbidities of aging, have resulted in end-organ disease and organ failure as a major cause of morbidity and mortality. Solid organ transplantation is a life-saving therapy for PWH who have organ failure, and the approval of the HIV Organ Policy Equity Act has opened and expanded opportunities for PWH to donate and receive organs. The current environment of organ transplantation for PWH will be reviewed and future directions of research and treatment will be discussed.
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33
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The future of HIV Organ Policy Equity Act is now: the state of HIV+ to HIV+ kidney transplantation in the United States. Curr Opin Organ Transplant 2020; 24:434-440. [PMID: 31145154 DOI: 10.1097/mot.0000000000000653] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW We report the current state of HIV+ to HIV+ kidney transplantation in the United States and remaining challenges in implementing this practice nationally. RECENT FINDINGS The HIV Organ Policy Equity (HOPE) Act, which was the first step in unlocking the potential of HIV+ organ donors, mandates clinical research on HIV+ to HIV+ transplantation. As of March 2019, there have been 57 HOPE donors, including both true and false positive HOPE donors resulting in more than 120 transplants. SUMMARY The HOPE Act, signed in 2013, reversed the federal ban on the transplantation of organs from HIV+ donors into HIV+ recipients. Ongoing national studies are exploring the safety, feasibility, and efficacy of both kidney and liver transplantation in this population. If successfully and fully implemented, HIV+ to HIV+ transplantation could attenuate the organ shortage for everyone waiting, resulting in a far-reaching public health impact.
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34
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Choudhury RA, Prins K, Dor Y, Moore HB, Yaffe H, Nydam TL. Uncontrolled donation after circulatory death improves access to kidney transplantation: A decision analysis. Clin Transplant 2020; 34:e13868. [PMID: 32259310 DOI: 10.1111/ctr.13868] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/06/2020] [Accepted: 03/27/2020] [Indexed: 02/06/2023]
Abstract
AIM Uncontrolled donation after cardiac death (uDCD) remains an underutilized source of kidney allografts in the United States. The objective of this study was to estimate the impact of the implementation of a uDCD program on transplantation rates and long-term survival for patients with end-stage renal disease (ESRD) in the United States. METHODS A decision-analytic Markov state transition model was created using medical decision-making software (DATA 3.5; TreeAge Software, Inc) to estimate the impact of an uDCD program on transplantation rates and patient survival. Additionally, sensitivity analysis of uDCD donor pool increase was modeled. All model statistic parameters were extracted from the literature. RESULTS A uDCD program increased the rate of transplant at 10 years (37.8%, Accept uDCD group, vs 35.9%, Reject uDCD group). At 10 years, overall survival for Accept uDCD was 55.6% compared to 54.8% in the Reject uDCD. CONCLUSIONS Uncontrolled DCD improves access to transplant for ESRD patients on the kidney transplant waitlist, thereby improving long-term survival.
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Affiliation(s)
- Rashikh A Choudhury
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Kas Prins
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Yoeli Dor
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Hunter B Moore
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Hillary Yaffe
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Trevor L Nydam
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
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35
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Heron JE, Bagnis CI, Gracey DM. Contemporary issues and new challenges in chronic kidney disease amongst people living with HIV. AIDS Res Ther 2020; 17:11. [PMID: 32178687 PMCID: PMC7075008 DOI: 10.1186/s12981-020-00266-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 02/22/2020] [Indexed: 12/27/2022] Open
Abstract
Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and mortality. The prevalence of CKD is rising, despite the widespread use of antiretroviral therapy (ART) and is increasingly related to prevalent non-infectious comorbidities (NICMs) and antiretroviral toxicity. There are great disparities evident, with the highest prevalence of CKD among PLWHIV seen in the African continent. The aetiology of kidney disease amongst PLWHIV includes HIV-related diseases, such as classic HIV-associated nephropathy or immune complex disease, CKD related to NICMs and CKD from antiretroviral toxicity. CKD, once established, is often relentlessly progressive and can lead to end-stage renal disease (ESRD). Identifying patients with risk factors for CKD, and appropriate screening for the early detection of CKD are vital to improve patient outcomes. Adherence to screening guidelines is variable, and often poor. The progression of CKD may be slowed with certain clinical interventions; however, data derived from studies involving PLWHIV with CKD are sparse and this represent an important area for future research. The control of blood pressure using angiotensin converting enzyme inhibitors and angiotensin receptor blockers, in particular, in the setting of proteinuria, likely slows the progression of CKD among PLWHIV. The cohort of PLWHIV is facing new challenges in regards to polypharmacy, drug-drug interactions and adverse drug reactions. The potential nephrotoxicity of ART is important, particularly as cumulative ART exposure increases as the cohort of PLWHIV ages. The number of PLWHIV with ESRD is increasing. PLWHIV should not be denied access to renal replacement therapy, either dialysis or kidney transplantation, based on their HIV status. Kidney transplantation amongst PLWHIV is successful and associated with an improved prognosis compared to remaining on dialysis. As the cohort of PLWHIV ages, comorbidity increases and CKD becomes more prevalent; models of care need to evolve to meet the new and changing chronic healthcare needs of these patients.
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Affiliation(s)
- Jack Edward Heron
- Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Corinne Isnard Bagnis
- Nephrology Department, Groupe Hospitalier Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
| | - David M Gracey
- Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
- Central Clinical School, The University of Sydney, Sydney, NSW, Australia.
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36
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Boyle SM, Fehr K, Deering C, Raza A, Harhay MN, Malat G, Ranganna K, Lee DH. Barriers to kidney transplant evaluation in HIV-positive patients with advanced kidney disease: A single-center study. Transpl Infect Dis 2020; 22:e13253. [PMID: 31994821 DOI: 10.1111/tid.13253] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 01/09/2020] [Accepted: 01/12/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND HIV-positive kidney transplant (KT) recipients have similar outcomes to HIV-negative recipients. However, HIV-positive patients with advanced kidney disease might face additional barriers to initiating the KT evaluation process. We sought to characterize comorbidities, viral control and management, viral resistance, and KT evaluation appointment rates in a cohort of KT evaluation-eligible HIV-positive patients. METHODS We included patients seen between January 1, 2008, and December 31, 2015, at a primary care HIV clinic who met KT evaluation eligibility by an estimated glomerular filtration rate ≤20 mL/min/1.73 meters2 or dialysis dependence. The primary outcome was a documented appointment for KT evaluation. RESULTS Of 3735 patients evaluated at the HIV primary clinic during the study period, 42 (1.6%) were KT evaluation-eligible patients. The median age was 47 years, 77% were male, and 95%, black. Median CD4 count was 328 cells/mm3 (IQR 175-461). Among the 63% percent with antiretroviral therapy (ART) prescription, 40% had viral loads >200 copies. Among patients with HIV resistance profiles (50%, n = 21), 52% had resistance to at least one class of ART. A majority (60%, n = 25) were scheduled for KT evaluation appointment, but of those, only 8% (n = 2) had evidence of appointments before dialysis dependence. Those without appointments had more schizophrenia (29% vs 4%, P = .02), resistance (78% vs 33%, P = .04), ART prescription (76% vs 48%, P = .04), and more kidney disease of unknown etiology (53% vs 8%, P = .02). CONCLUSION Kidney transplant evaluation-eligible HIV-positive patients had a high rate of evaluation appointments, but a low rate of preemptive evaluation appointments. Schizophrenia and viral resistance disproportionally affected patients without evaluation appointments. These data precede the recommendation for universal ART for all HIV+ patients, regardless of CD4 count and viral load, and must be interpreted in the context of this limitation.
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Affiliation(s)
- Suzanne M Boyle
- Division Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania
| | - Kallie Fehr
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Catylin Deering
- Division of Infectious Disease, Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio
| | - Abbas Raza
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Meera N Harhay
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.,Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania.,Tower Health System, Tower Health Transplant Institute, West Reading, Pennsylvania
| | - Gregory Malat
- Department of Medicine, Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Karthik Ranganna
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.,Tower Health System, Tower Health Transplant Institute, West Reading, Pennsylvania
| | - Dong Heun Lee
- Division of Infectious Disease and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania
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37
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Therapeutic management of HIV-infected patients with chronic kidney disease. J Nephrol 2020; 33:699-713. [PMID: 32020538 DOI: 10.1007/s40620-020-00701-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
CKD and HIV infection are two chronic diseases impacting heavily on the survival of the affected patients. The interplay between HIV infection and chronic kidney disease (CKD) is complex and interactions occur at multiple levels. Approach to the management of HIV-infected patients requires special attention to face the numerous therapeutic difficulties ranging from drug-drug interactions to drug-toxicity. The most effective strategy is targeted to suppression of HIV viral load, as it dramatically changes the prognosis of the patients as well as prevents the development of HIV-associated kidney disease. As shown in this review, the approach to the therapeutic management of CKD in the setting of HIV infection varies in relation to the degree of renal impairment.
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38
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Durand CM, Werbel W, Doby B, Brown D, Desai NM, Malinis M, Price J, Chin-Hong P, Mehta S, Friedman-Moraco R, Turgeon NA, Gilbert A, Morris MI, Stosor V, Elias N, Aslam S, Santos CAQ, Hand JM, Husson J, Pruett TL, Agarwal A, Adebiyi O, Pereira M, Small CB, Apewokin S, Heun Lee D, Haidar G, Blumberg E, Mehta SA, Huprikar S, Florman SS, Redd AD, Tobian AAR, Segev DL. Clarifying the HOPE Act landscape: The challenge of donors with false-positive HIV results. Am J Transplant 2020; 20:617-619. [PMID: 31675457 PMCID: PMC7132607 DOI: 10.1111/ajt.15681] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Christine M Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - William Werbel
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brianna Doby
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Diane Brown
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Niraj M Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Maricar Malinis
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Jennifer Price
- Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Peter Chin-Hong
- Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Shikha Mehta
- Department of Medicine, University of Alabama School of Medicine, Birmingham, Alabama
| | | | | | - Alexander Gilbert
- Medstar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington, DC
| | - Michele I Morris
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida
| | - Valentina Stosor
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Nahel Elias
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Saima Aslam
- Department of Medicine, University of California, San Diego, San Diego, California
| | - Carlos A Q Santos
- Department of Medicine, Rush University Medical Center, Chicago, Illinois
| | - Jonathan M Hand
- Department of Medicine, University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, Louisiana
| | - Jennifer Husson
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Timothy L Pruett
- Department of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota
| | - Avinash Agarwal
- Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia
| | - Oluwafisayo Adebiyi
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Marcus Pereira
- Department of Medicine, Columbia University Irving Medical Center, New York, New York
| | - Catherine B Small
- Department of Medicine, Weill Medical College of Cornell University, New York, New York
| | - Senu Apewokin
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Dong Heun Lee
- Department of Medicine, Drexel University, Philadelphia, Pennsylvania
| | - Ghady Haidar
- Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Emily Blumberg
- Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Sapna A Mehta
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Shirish Huprikar
- Department of Medicine, Icahn School of Medicine, New York, New York
| | - Sander S Florman
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, New York
| | - Andrew D Redd
- Division of Intramural Research, NIAID, NIH, Bethesda, Maryland
| | - Aaron A R Tobian
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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39
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Tourret J, Guiguet M, Lassalle M, Grabar S, Lièvre L, Isnard-Bagnis C, Barrou B, Costagliola D, Couchoud C, Abgrall S, Tézenas Du Montcel S. Access to the waiting list and to kidney transplantation for people living with HIV: A national registry study. Am J Transplant 2019; 19:3345-3355. [PMID: 31206243 DOI: 10.1111/ajt.15500] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 05/27/2019] [Accepted: 06/03/2019] [Indexed: 01/25/2023]
Abstract
We compared access to a kidney transplantation (KT) waiting list (WL) and to KT between people living with HIV (PLHIV) and HIV-uninfected controls. Using the REIN (the national Renal Epidemiology and Information Network registry), we included all PLHIV initiating dialysis in France throughout 2006-2010 and HIV-uninfected controls matched for age, sex, year of dialysis initiation, and the existence of a diabetic nephropathy. Patients were prospectively followed until December 2015. We used a competitive risk approach to assess the cumulative incidence of enrollment on WL and of KT, with death as a competing event (subdistribution hazard ratio adjusted on comorbidities, asdHR). There were 255 PLHIV in the REIN (median age 47 years) of whom 180 (71%) were also found in the French Hospital Database on HIV (FHDH-ANRS CO4) including 126 (70%) known to be on antiretroviral therapy with HIV viral suppression (VS). Five years after dialysis initiation, 65%, and 76%, of treated PLHIV with VS, and of HIV-uninfected controls were enrolled on a WL (asdHR 0.68; 95% CI 0.50-0.91). Access to KT was also less frequent and delayed for treated PLHIV with VS (asdHR 0.75, 95% CI, 0.52-1.10). PLHIV continue to face difficulties to access KT.
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Affiliation(s)
- Jérôme Tourret
- Sorbonne Université, Paris, France.,INSERM UMR1138, Paris, France.,Assistance Publique-Hôpitaux de Paris AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Département d'urologie, néphrologie et transplantation, Paris, France
| | - Marguerite Guiguet
- Sorbonne Université, Paris, France.,INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP UMR-S1136, Paris, France
| | - Mathilde Lassalle
- REIN registry, Agence de la biomédecine, Saint Denis La Plaine, France
| | - Sophie Grabar
- INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP UMR-S1136, Paris, France.,Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Assistance Publique-Hôpitaux de Paris AP-HP, Hôpitaux Universitaires Cochin Broca Hôtel-Dieu, Unité de Biostatistique et d'épidémiologie, Paris, France
| | - Laurence Lièvre
- REIN registry, Agence de la biomédecine, Saint Denis La Plaine, France
| | - Corinne Isnard-Bagnis
- Sorbonne Université, Paris, France.,Assistance Publique-Hôpitaux de Paris AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Département d'urologie, néphrologie et transplantation, Paris, France
| | - Benoit Barrou
- Sorbonne Université, Paris, France.,Assistance Publique-Hôpitaux de Paris AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Département d'urologie, néphrologie et transplantation, Paris, France
| | - Dominique Costagliola
- INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP UMR-S1136, Paris, France
| | - Cécile Couchoud
- REIN registry, Agence de la biomédecine, Saint Denis La Plaine, France.,Université Claude Bernard Lyon I, Lyon, France.,UMR CNRS 5558, Laboratoire de Biostatistique en Santé, Lyon, France
| | - Sophie Abgrall
- INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP UMR-S1136, Paris, France.,Université Paris-Saclay, Univ. Paris Sud, Paris, France.,UVSQ, CESP INSERM U1018, Le Kremlin-Bicêtre, France.,Assistance Publique-Hôpitaux de Paris AP-HP, Hôpital Antoine Béclère, Service de Médecine interne, Clamart, France
| | - Sophie Tézenas Du Montcel
- Sorbonne Université, Paris, France.,INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP UMR-S1136, Paris, France.,Assistance Publique-Hôpitaux de Paris AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
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40
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Camargo JF, Pallikkuth S, Moroz I, Natori Y, Alcaide ML, Rodriguez A, Guerra G, Burke GW, Pahwa S. Pretransplant Levels of C-Reactive Protein, Soluble TNF Receptor-1, and CD38+HLADR+ CD8 T Cells Predict Risk of Allograft Rejection in HIV+ Kidney Transplant Recipients. Kidney Int Rep 2019; 4:1705-1716. [PMID: 31844807 PMCID: PMC6895601 DOI: 10.1016/j.ekir.2019.08.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 08/12/2019] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION HIV-positive (HIV+) kidney transplant recipients exhibit a 2- to 3-fold increased risk of allograft rejection. Dysregulated immune activation in HIV infection persists despite successful antiretroviral therapy and is associated with non-AIDS morbidity, including renal disease. We hypothesized that the pathological levels of inflammation and immune activation associated with chronic HIV infection could have clinical utility in the prediction of rejection in HIV+ kidney recipients. METHODS Prospective cohort study of 22 HIV-negative (HIV-; donor) to HIV+ (recipient) kidney transplant recipients who underwent biomarker assessment pretransplant and were subsequently followed for development of acute rejection. Plasma levels of markers of inflammation (soluble tumor necrosis factor receptor 1 [sTNF-R1] and C-reactive protein [CRP]) and microbial translocation (soluble CD14 and lipopolysaccharide) were measured by enzyme-linked immunosorbent assay or chromogenic endpoint assay. Levels of activated (CD38+HLADR+) CD4+ and CD8+ T cells, and T regulatory cells (CD4+CD25highFoxP3+) were measured by flow cytometry. RESULTS Among the biomarkers evaluated, only the pretransplant levels of sTNF-R1, CRP, and frequencies of CD38+HLADR+ CD8 T cells, were found to be at significantly higher levels among patients who experienced biopsy-proven acute rejection. Confirming our hypothesis, patients with high pretransplant levels of sTNF-R1 or activated CD8+ T cells had a significantly increased 200-day cumulative incidence of biopsy-proven acute rejection (0 vs. 38% for both; P = 0.01). Similarly, pretransplant CRP levels higher than 5 μg/ml were associated with increased risk of acute rejection within the first 6 months post-transplant (0 vs. 43%; P = 0.01). CONCLUSION Biomarker-based identification of HIV+ recipients at increased risk for rejection might facilitate individualized induction immunosuppression regimens in this vulnerable patient population.
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Affiliation(s)
- Jose F. Camargo
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Suresh Pallikkuth
- Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Ilona Moroz
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Yoichiro Natori
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Maria L. Alcaide
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Allan Rodriguez
- Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | | | | | - Savita Pahwa
- Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA
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41
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Zheng X, Gong L, Xue W, Zeng S, Xu Y, Zhang Y, Hu X. Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis. AIDS Res Ther 2019; 16:37. [PMID: 31747972 PMCID: PMC6868853 DOI: 10.1186/s12981-019-0253-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 11/09/2019] [Indexed: 01/01/2023] Open
Abstract
Background Kidney transplantation is now a viable alternative to dialysis in HIV-positive patients who achieve good immunovirological control with the currently available antiretroviral therapy regimens. This systematic review and meta-analysis investigate the published evidence of outcome and risk of kidney transplantation in HIV-positive patients following the PRISMA guidelines. Methods Searches of PubMed, the Cochrane Library and EMBASE identified 27 cohort studies and 1670 case series evaluating the survival of HIV-positive kidney transplant patients published between July 2003 and May 2018. The regimens for induction, maintenance therapy and highly active antiretroviral therapy, acute rejection, patient and graft survival, CD4 count and infectious complications were recorded. We evaluated the patient survival and graft survival at 1 and 3 years respectively, acute rejection rate and also other infectious complications by using a random-effects analysis. Results At 1 year, patient survival was 0.97 (95% CI 0.95; 0.98), graft survival was 0.91 (95% CI 0.88; 0.94), acute rejection was 0.33 (95% CI 0.28; 0.38), and infectious complications was 0.41 (95% CI 0.34; 0.50), and at 3 years, patient survival was 0.94 (95% CI 0.90; 0.97) and graft survival was 0.81 (95% CI 0.74; 0.87). Conclusions With careful selection and evaluation, kidney transplantation can be performed with good outcomes in HIV-positive patients.
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Hwang HP, Yu HC, Kang KP, Kim W, Park SK, Ku JS, Kim H, Lee S. Kidney transplantation in human immunodeficiency virus-infected patients: a report of two cases and a review of the literatures. KOREAN JOURNAL OF TRANSPLANTATION 2019; 33:60-64. [PMID: 35769407 PMCID: PMC9186908 DOI: 10.4285/jkstn.2019.33.3.60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 07/15/2019] [Accepted: 07/15/2019] [Indexed: 12/04/2022] Open
Abstract
Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for transplantation because of concerns about HIV disease progression due to immunosuppression. Since potent antiretroviral therapies (ARTs) have become widely available, the prognosis of HIV-infected kidney transplant recipients has dramatically improved. Recent results of prospective multicenter trials on kidney transplantation (KT) in HIV-positive candidates have demonstrated the success and challenges of transplantation in this population. Several studies have reported comparable patient and graft outcomes between HIV-infected and HIV-uninfected recipients after KT in the era of potent combined ARTs. We report two cases of HIV-infected patients who underwent KT at our hospital. In this paper, we present a detailed report of two cases and provide a short review of the existing literature.
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Affiliation(s)
- Hong Pil Hwang
- Department of General Surgery, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Hee Chul Yu
- Department of General Surgery, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Kyung Pyo Kang
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National Universi
| | - Won Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National Universi
| | - Sung Kwang Park
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National Universi
| | - Jeong Sang Ku
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National Universi
| | - Hyeongwan Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National Universi
| | - Sik Lee
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National Universi
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43
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Heart or lung transplant outcomes in HIV-infected recipients. J Heart Lung Transplant 2019; 38:1296-1305. [PMID: 31636044 DOI: 10.1016/j.healun.2019.09.011] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 09/13/2019] [Accepted: 09/19/2019] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Limited published data exist on outcomes related to heart and/or lung transplantation in human immunodeficiency virus (HIV)-infected individuals. METHODS We conducted a multicenter retrospective study of heart and lung transplantation in HIV-infected patients and describe key transplant- and HIV-related outcomes. RESULTS We identified 29 HIV-infected thoracic transplant recipients (21 heart, 7 lung, and 1 heart and/or lung) across 14 transplant centers from 2000 through 2016. Compared with an International Society for Heart and Lung Transplantation registry cohort, we demonstrated similar 1-, 3-, and 5-year patient and allograft survivals for each organ type with a median follow up of 1,064 (range, 184-3,745) days for heart and 1,540 (range, 116-3,206) days for lung recipients. At 1 year, significant rejection rates were high (62%) for heart transplant recipients (HTRs). Risk factors for rejection were inconclusive, likely because of small numbers, but may be related to cautious early immunosuppression and infrequent use of induction therapy. Pulmonary bacterial infections were high (86%) for lung transplant recipients (LTRs). Median CD4 counts changed from baseline to 1 year from 399 to 411 cells/µl for HTRs and 638 to 280 cells/µl for LTRs. Acquired immunodeficiency syndrome-related events, including infections and malignancies, were rare. Rates of severe renal dysfunction suggest a need to modify nephrotoxic anti-retrovirals and/or immunosuppressants. CONCLUSIONS HIV-infected HTRs and LTRs have similar survival rates to their HIV-uninfected counterparts. Although optimal immunosuppression is not defined, it should be at least as aggressive as that for HIV-uninfected recipients. Such data may help pave the way for the use of hearts and lungs from HIV-infected donors in HIV-infected recipients through HIV Organ Policy Equity Act protocols.
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44
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Alfano G, Cappelli G, Fontana F, Di Lullo L, Di Iorio B, Bellasi A, Guaraldi G. Kidney Disease in HIV Infection. J Clin Med 2019; 8:jcm8081254. [PMID: 31430930 PMCID: PMC6722524 DOI: 10.3390/jcm8081254] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Revised: 08/07/2019] [Accepted: 08/12/2019] [Indexed: 12/13/2022] Open
Abstract
Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of long-term exposure of ART. Chronic kidney disease (CKD) is a common comorbidity in this population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD) and significantly affect quality of life and risk of death. Herein, we review current understanding of renal involvement in PLWH, mechanisms and risk factors for CKD as well as strategies for early recognition of renal dysfunction and best care of CKD.
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Affiliation(s)
- Gaetano Alfano
- Surgical, Medical and Dental Department of Morphological Sciences, Section of Nephrology, University of Modena and Reggio Emilia, 41125 Modena, Italy.
- Nephrology Dialysis and Transplant Unit, University Hospital of Modena, 41125 Modena, Italy.
| | - Gianni Cappelli
- Surgical, Medical and Dental Department of Morphological Sciences, Section of Nephrology, University of Modena and Reggio Emilia, 41125 Modena, Italy
- Nephrology Dialysis and Transplant Unit, University Hospital of Modena, 41125 Modena, Italy
| | - Francesco Fontana
- Nephrology Dialysis and Transplant Unit, University Hospital of Modena, 41125 Modena, Italy
| | - Luca Di Lullo
- Department of Nephrology and Dialysis, "L. Parodi-Delfino" Hospital, 00034 Colleferro, Italy
| | - Biagio Di Iorio
- Department of Medicine, AORN "Antonio Cardarelli", 80131 Naples, Italy
| | - Antonio Bellasi
- Department of Research, Innovation, Brand Reputation, Ospedale di Bergamo, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Giovanni Guaraldi
- Clinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41125 Modena, Italy
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45
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Zhou X, Mandal M, Suarez-Pierre A, Krishnan A, Fraser CD, Whitman GJR, Higgins RSD, Mandal K. Disseminated Intravascular Coagulation Following Heart Transplant in an HIV-infected Recipient: Case Report and Review of the Literature. Transplant Direct 2019; 5:e444. [PMID: 31165079 PMCID: PMC6511447 DOI: 10.1097/txd.0000000000000892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 02/07/2019] [Accepted: 03/03/2019] [Indexed: 11/25/2022] Open
Affiliation(s)
- Xun Zhou
- Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
| | | | | | - Aravind Krishnan
- Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
| | - Charles D Fraser
- Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
| | | | | | - Kaushik Mandal
- Division of Cardiac Surgery, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA
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46
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Liyanage L, Muzaale AD, Henderson ML, Durand CM. Living kidney donation in individuals with hepatitis C and HIV infection: rationale and emerging evidence. CURRENT TRANSPLANTATION REPORTS 2019; 6:167-176. [PMID: 32855901 PMCID: PMC7449146 DOI: 10.1007/s40472-019-00242-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
PURPOSE OF REVIEW HIV-infected (HIV+) and hepatitis C virus-infected (HCV+) individuals with end-stage renal disease (ESRD) have decreased access to kidney transplantation. With new opportunities provided by the HIV Organ Policy Equity (HOPE) Act and direct-acting antivirals (DAAs) for HCV, we explore the potential risks and benefits of living donor kidney transplantation from HIV+ or HCV+ donors, from the perspective of both donor health and recipient outcomes. RECENT FINDINGS The HOPE Act permits organ donation from both deceased and living HIV+ persons to HIV+ recipients; however, there is only clinical experience with HIV+ deceased donors to date. Empirical evidence demonstrates a low but acceptable risk of ESRD in potential HIV+ living donors without comorbidities who have well-controlled infection in the absence of donation. With the availability of potent DAAs for eradication of HCV infection, growing evidence shows good outcomes with HCV seropositive and/or viremic deceased kidney donors, providing rationale to consider HCV+ living donors. SUMMARY HIV+ and HCV+ living donor kidney transplantation may improve access to transplant for vulnerable ESRD populations. Careful evaluation and monitoring are warranted to mitigate potential risks to donors and recipients.
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Affiliation(s)
- Luckmini Liyanage
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Abimereki D. Muzaale
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Macey L. Henderson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Christine M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
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47
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Kizilbash SJ, Rheault MN, Wang Q, Vock DM, Chinnakotla S, Pruett T, Chavers BM. Kidney transplant outcomes associated with the use of increased risk donors in children. Am J Transplant 2019; 19:1684-1692. [PMID: 30582274 DOI: 10.1111/ajt.15231] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 12/11/2018] [Accepted: 12/12/2018] [Indexed: 01/25/2023]
Abstract
Increased risk donors (IRDs) may inadvertently transmit blood-borne viruses to organ recipients through transplant. Rates of IRD kidney transplants in children and the associated outcomes are unknown. We used the Scientific Registry of Transplant Recipients to identify pediatric deceased donor kidney transplants that were performed in the United States between January 1, 2005 and December 31, 2015. We used the Cox regression analysis to compare patient and graft survival between IRD and non-IRD recipients, and a sequential Cox approach to evaluate survival benefit after IRD transplants compared with remaining on the waitlist and never accepting an IRD kidney. We studied 328 recipients with and 4850 without IRD transplants. The annual IRD transplant rates ranged from 3.4% to 13.2%. IRDs were more likely to be male (P = .04), black (P < .001), and die from head trauma (P = .006). IRD recipients had higher mean cPRA (0.085 vs 0.065, P = .02). After multivariate adjustment, patient survival after IRD transplants was significantly higher compared with remaining on the waitlist (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.26-0.88, P = .018); however, patient (aHR: 0.93, 95% CI: 0.54-1.59, P = .79) and graft survival (aHR: 0.89, 95% CI: 0.70-1.13, P = .32) were similar between IRD and non-IRD recipients. We recommend that IRDs be considered for transplant in children.
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Affiliation(s)
- Sarah J Kizilbash
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
| | - Michelle N Rheault
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
| | - Qi Wang
- Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minneapolis
| | - David M Vock
- Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota
| | | | - Tim Pruett
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Blanche M Chavers
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
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48
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Werbel WA, Durand CM. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers. Curr HIV/AIDS Rep 2019; 16:191-203. [PMID: 31093920 PMCID: PMC6579039 DOI: 10.1007/s11904-019-00440-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW End-stage organ disease prevalence is increasing among HIV-infected (HIV+) individuals. Trial and registry data confirm that solid organ transplantation (SOT) is efficacious in this population. Optimizing access to transplant and decreasing complications represent active frontiers. RECENT FINDINGS HIV+ recipients historically experienced 2-4-fold higher rejection. Integrase strand transferase inhibitors (INSTIs) minimize drug interactions and may reduce rejection along with lymphodepleting induction immunosuppression. Hepatitis C virus (HCV) coinfection has been associated with inferior outcomes, yet direct-acting antivirals (DAAs) may mitigate this. Experience in South Africa and the US HIV Organ Policy Equity (HOPE) Act support HIV+ donor to HIV+ recipient (HIV D+/R+) transplantation. SOT is the optimal treatment for end-stage organ disease in HIV+ individuals. Recent advances include use of INSTIs and DAAs in transplant recipients; however, strategies to improve access to transplant are needed. HIV D+/R+ transplantation is under investigation and may improve access and provide insights for HIV cure and pathogenesis research.
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Affiliation(s)
- William A. Werbel
- Department of Medicine, Johns Hopkins University School
of Medicine, Baltimore, MD
| | - Christine M. Durand
- Department of Medicine, Johns Hopkins University School
of Medicine, Baltimore, MD
- Sidney Kimmel Cancer Center, Johns Hopkins University
School of Medicine, Baltimore, MD
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49
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Shelton BA, Berdahl G, Sawinski D, Linas BP, Reese PP, Mustian MN, Reed RD, MacLennan PA, Locke JE. Optimal timing of hepatitis C treatment among HIV/HCV coinfected ESRD patients: Pre- vs posttransplant. Am J Transplant 2019; 19:1806-1819. [PMID: 30589503 PMCID: PMC6538449 DOI: 10.1111/ajt.15239] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 11/28/2018] [Accepted: 12/13/2018] [Indexed: 02/06/2023]
Abstract
Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.
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Affiliation(s)
- Brittany A. Shelton
- University of Alabama at Birmingham Comprehensive Transplant Institute, Birmingham, AL, USA
| | - Gideon Berdahl
- University of Alabama at Birmingham Comprehensive Transplant Institute, Birmingham, AL, USA
| | - Deirdre Sawinski
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | | | - Peter P. Reese
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Margaux N. Mustian
- University of Alabama at Birmingham Comprehensive Transplant Institute, Birmingham, AL, USA
| | - Rhiannon D. Reed
- University of Alabama at Birmingham Comprehensive Transplant Institute, Birmingham, AL, USA
| | - Paul A. MacLennan
- University of Alabama at Birmingham Comprehensive Transplant Institute, Birmingham, AL, USA
| | - Jayme E. Locke
- University of Alabama at Birmingham Comprehensive Transplant Institute, Birmingham, AL, USA
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50
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Expanding deceased donor kidney transplantation: medical risk, infectious risk, hepatitis C virus, and HIV. Curr Opin Nephrol Hypertens 2019; 27:445-453. [PMID: 30169460 DOI: 10.1097/mnh.0000000000000456] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Due to the organ shortage, which prevents over 90 000 individuals in the United States from receiving life-saving transplants, the transplant community has begun to critically reevaluate whether organ sources that were previously considered too risky provide a survival benefit to waitlist candidates. RECENT FINDINGS Organs that many providers were previously unwilling to use for transplantation, including kidneys with a high Kidney Donor Profile Index or from increased risk donors who have risk factors for window period hepatitis C virus (HCV) and HIV infection, have been shown to provide a survival benefit to transplant waitlist candidates compared with remaining on dialysis. The development of direct-acting antivirals to cure HCV infection has enabled prospective trials on the transplantation of organs from HCV-infected donors into HCV-negative recipients, with promising preliminary results. Changes in legislation through the HIV Organ Policy Equity Act have legalized transplantations from HIV-positive deceased donors to HIV-positive recipients for the first time in the United States. SUMMARY Critical reexamination of deceased donor organs that were previously discarded has resulted in greater utilization of these organs, an increased number of deceased donor transplants, and the provision of life-saving treatment to more transplant waitlist candidates.
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