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Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and candidiasis (22%). The infected cohort was more likely to receive basiliximab, undergo lung transplantation, or identify as White. Higher rates of aspergillosis were seen in this lung cohort than previously reported.
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Background. Although mammalian target of rapamycin inhibitors (mTORi) are associated with a lower incidence of the first episode of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving calcineurin inhibitors (CNIs), the efficacy and safety of the conversion from the antimetabolite to an mTORi for the prevention of CMV recurrence are unknown. Methods. In this single-center prospective randomized...
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Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that...
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Potent immunosuppressive drugs have been introduced into clinical care for solid organ transplant recipients. It is now time to guide these drugs on an individual level to optimize their efficacy. An ideal tool simultaneously detects overimmunosuppression and underimmunosuppression, is highly standardized, and is straightforward to implement into routine. Randomized controlled interventional trials are crucial to demonstrate clinical value. To date, proposed assays have mainly focused on the...
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Background Belatacept improves long-term graft survival, but control of some primary viral infections may be impaired. We evaluated the impact of belatacept and tacrolimus on cytomegalovirus (CMV) viral control, remission and relapse in CMV high-risk and moderate-risk recipients. Methods Using a multistate Markov model, we evaluated viral load state transitions of 173 kidney transplant recipients with at least one episode of viremia within 1 year after transplant: state 1, undetectable/low...
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Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient...
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Abstract Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The “net state of immune suppression” is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function...
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Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months...
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While some biologicals have been routinely used in solid organ and hematopoietic stem cell transplant patients for years, a number of newer compounds have been added to the armamentarium for varying indications spanning from the underlying disease to complications of transplantation. This chapter aims at describing the infectious risk of a selection of compounds. The specific chapters list a number of recommendations to consider for infection prevention, in addition to the standard...
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Over the last half a century, there have been innumerable advances in our understanding of the human immune system. We now have a better understanding not only of the ways our innate and adaptive immune pathways interact to seek out and control infection and malignancy, but we are closer to understanding some of the control mechanisms behind tissue rejection. Organ allograft rejection, with consequent loss of graft function, remains one of the most challenging problems facing solid organ...
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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...
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These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation provide an update on potential drug-drug interactions between anti-infectives and immunosuppressants, which are most notable with calcineurin and mTOR inhibitors. Drug-drug interactions may occur through pharmacokinetic mechanisms leading to altered drug concentrations of either the anti-infective or immunosuppressive drug, or by pharmacodynamic interactions increasing or...
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GUIDELINES
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