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Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers.

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.

SUBMITTER: Werbel WA

PROVIDER: S-EPMC6579039 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers.

Werbel William A WA Durand Christine M CM

Current HIV/AIDS reports 20190601 3

<h4>Purpose of review</h4>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.<h4>Recent findings</h4>HIV+ recipients historically experienced 2-4-fold higher rejection. Integrase strand transferase inhibitors (INSTIs) minimize drug interactions and may reduce rejection ...[more]

PMID: 31093920

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Project description:The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (?65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

Project description:BackgroundLife-long immunosuppressive treatment after liver transplantation (LT) prevents graft rejection but predisposes the LT recipient to infections. Herpesvirus infections are associated with morbidity and mortality among LT recipients. Among those, especially cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after LT. The aim of this study is to provide an in-depth characterization of the cellular immune response against CMV and VZV infections in LT recipients and identify potential risk factors for infection.MethodsThe Herpesvirus Infections in Solid Organ Transplant Recipients - Liver Transplant Study (HISTORY) consists of an epidemiological and immunological substudy. The epidemiological substudy is a retrospective observational cohort study that includes all patients who underwent LT in Denmark between 2010 and 2023 (N ≈ 500). Using data from nationwide hospital records and national health registries, the incidence of and clinical risk factors for CMV and VZV infections will be determined. The immunological substudy is an explorative prospective observational cohort study including patients enlisted for LT in Denmark during a 1.5-year period (N > 80). Participants will be followed with scheduled blood samples until 12 months after LT. CMV- and VZV-derived peptides will be predicted for their likelihood to be presented in participants based on their HLA type. Peptide-MHC complexes (pMHC) will be produced to isolate CMV- and VZV-specific T cells from peripheral blood mononuclear cells before and after CMV and VZV infection. Their frequency, T cell receptor sequences, and phenotypic characteristics will be examined, and in a subset of participants, CMV- and VZV-specific T cells will be expanded ex vivo.DiscussionThis study will provide novel insight into T cell immunity required for viral control of CMV and VZV and has the potential to develop a prediction model to identify LT recipients at high risk for infection based on a combination of clinical and immunological data. Furthermore, this study has the potential to provide proof-of-concept for adoptive T cell therapy against CMV and VZV. Combined, this study has the potential to reduce the burden and consequence of CMV and VZV infections and improve health and survival in LT recipients.Trial registrationClinicalTrials.gov (NCT05532540), registered 8 September 2022.

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Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers.

Publications

Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers.

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