Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients

Cooper, Megan H; Dunne, Ian; Kuten, Samantha A.; Curtis, Anna Lisa; Graviss, Edward A.; Nguyen, Duc T.; Hobeika, Mark J.; Gaber, A. Osama

doi:10.1016/j.transproceed.2020.10.003

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…Initially, we switched to a combination of an integrase inhibitor (II) and a nucleoside reverse transcriptase inhibitor (NRTI) and then to a combination of an II and two NRTIs. The strategy of changing ARV regimen to one without PIs should always be considered, given that PIs determines high intrapatient tacrolimus variability, decreased graft function and a significantly higher rate of short-term rejection [17,18]. We did not experience degradation of kidney graft function, despite tacrolimus overexposure, rejection or development of anti-HLA antibodies.…”

Section: Discussionmentioning

confidence: 98%

HIV and kidney transplantation in Romania: The index case

Sorohan,

Ismail,

Oprea

et al. 2024

Romanian Journal of Internal Medicine

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Introduction Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients. Case presentation We present the case of a 29-year-old female patient with HIV and end-stage renal disease (ESRD) who performed a KT from a related living donor in March 2022. KT immediate evolution was favorable. No transplant-related complications were reported. HIV viral load remained undetectable and CD4+ T cells were constantly > 500 cell/ μL, during the 18 months of follow-up. The main challenge in our case was the drug interaction between the protease inhibitor-based regimen and tacrolimus. This led to tacrolimus overdose, and, subsequently, change in ARV therapy. ARV switching was performed on a regimen based on integrase inhibitor and nucleoside reverse transcriptase inhibitors. After the ARV change, the therapeutic level of tacrolimus was easily reached and maintained. Kidney graft function remained normal during follow-up, despite tacrolimus overexposure, and no rejection or anti-HLA antibodies were observed. Another challenge was related to the donor's hepatitis C virus status (positive antibodies, negative nucleic acid test). The recipient did not develop seroconversion or detectable viremia at 3-, 6-, 12- and 18-months post-KT. Conclusion We reported the first case of a successful KT in an ESRD patient with HIV in Romania, in whom the post-transplant evolution was favorable.

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Section: Discussionmentioning

confidence: 98%

HIV and kidney transplantation in Romania: The index case

Sorohan,

Ismail,

Oprea

et al. 2024

Romanian Journal of Internal Medicine

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“…Ideally, this should be done at least 3–6 months prior to transplantation [13]. Avoidance of protease inhibitor-based regimens provides an easier handling of posttransplant immunosuppression, reduces the frequency of CNI level assessments, could reduce the risk of rejection and CNI-associated nephrotoxicity [26,27].…”

Section: Pretransplant Selection Processmentioning

confidence: 99%

“…[9,10,13,14]. Notwithstanding their advantages, the main drawback of CNI remains drug interactions with ART, such as protease inhibitors and nonnucleoside reverse transcriptase inhibitors [27,37,38].…”

Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Immunosuppression in HIV-positive kidney transplant recipients

Sorohan

Ismail

Leca

2023

Current Opinion in Organ Transplantation

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Purpose of study The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients. Recent findings Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided. Summary Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR.

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“…73 High intra-patient variability in calcineurin inhibitor (CNI) levels because of pharmacokinetic interactions with protease inhibitor (PI)-containing ART and consequent underimmunosuppression is another possible explanation. 74 The role of the immunosuppressive regimen in mitigating the risk of acute rejection in PLWH has become clearer over the last decade. Antibody induction therapy was initially withheld because of concerns about prolonged lymphodepletion and the risk of infection.…”

Section: Posttransplant Outcomes and Immunosuppression Managementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expanding Access to Organ Transplant for People Living With HIV: Can Policy Catch Up to Outcomes Data?

Chandran,

Stock,

Roll

2023

Transplantation

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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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Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients

Cited by 9 publications

References 17 publications

HIV and kidney transplantation in Romania: The index case

HIV and kidney transplantation in Romania: The index case

Immunosuppression in HIV-positive kidney transplant recipients

Expanding Access to Organ Transplant for People Living With HIV: Can Policy Catch Up to Outcomes Data?

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