Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir

Bickel, Markus; Anadol, Evrim; Vogel, Martin; Hofmann, Wolf Peter; Hentig, Nils von; Kuetscher, Johannes; Kurowski, Michael; Moench, C.; Lennemann, Tessa; Lutz, Thomas; Bechstein, Wolf O.; Brodt, H.-R.; Rockstroh, Jürgen K.

doi:10.1093/jac/dkq054

Cited by 34 publications

(38 citation statements)

References 18 publications

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“…36,38,[42][43][44][45][46][47][48][49][50] Moreover, in patients on RTV-boosted PIs even higher drastic dosage reductions up to 120-fold are necessary to achieve therapeutic through levels of tacrolimus, cyclosporine, and sirolimus. 7,35,37,38,42,45,47,[51][52][53][54][55][56][57][58][59][60][61][62][63][64] Initiation of a posttransplant CNI dosing strategy similar to that used in a non-HIV positive patient can immediate lead to extremely high persistent CNI inhibitor levels and concurrent (nephro)toxicity [59]. CNI half life is prolonged 5-to 20-fold because of the systemic inhibition of CYP 3A and Pgp, resulting in dosing regimens of 0.5-1 mg once weekly for tacrolimus and 25 mg every 1-2 days for cyclosporine in kidney and liver transplant recipients.…”

Section: Protease Inhibitorsmentioning

confidence: 99%

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

Maarseveen

Rogers

Trofe‐Clark

et al. 2012

AIDS Patient Care and STDs

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Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, as witnessed by high rates of allograft rejection and drug toxicity, but the profound drug-drug interactions between immunosuppressants and cART, especially protease inhibitors (PIs) also play an important role. Caution and frequent drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients. Furthermore, the pharmacokinetics of glucocorticoids and mTOR inhibitors are seriously affected by PIs. With the introduction of integrase inhibitors, CCR5-antagonists and fusion inhibitors which cause significantly less pharmacokinetic interactions, have minor overlapping toxicity, and offer the advantage of pharmacodynamic synergy, it is time to revaluate what may be considered the optimal antiretroviral regimen in SOT recipients. In this review we provide a brief overview of the recent success of SOT in the HIV population, and an update on the pharmacokinetic and pharmacodynamic interactions between currently available cART and immunosuppressants in HIV-infected patients, who underwent SOT.

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Section: Protease Inhibitorsmentioning

confidence: 99%

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

Maarseveen

Rogers

Trofe‐Clark

et al. 2012

AIDS Patient Care and STDs

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“…With the inhibition of the CYP3A enzyme system, tacrolimus was recommended at 0.5 to 1 mg weekly to achieve a trough level of 8 to 12 ng/mL. [12][13][14][15] In conclusion, transplant is the best replacement therapy in HIV-positive end-stage kidney disease patients with controlled AIDS management under highly active antiretroviral therapy.…”

Section: Discussionmentioning

confidence: 99%

Kidney Transplant in a Human Immunodeficiency Virus-Positive Patient: Case Report of Drug Interactions

Yılmaz¹,

Gökengin²,

Bozbıyık³

et al. 2023

Exp Clin Transplant

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End-stage renal disease in the human immunodeficiency virus-positive population is increasing. Kidney transplant is the optimal therapy for this population rather than dialysis modalities if some criteria are met. These include undetectable plasma human immunodeficiency virus RNA, CD4 cell count over 200 cells/µL, and the absence of any AIDS-defining illness. Here, we describe the first living-donor kidney transplant in a human immunodeficiency virus-positive recipient in Turkey. The patient, a 52-year-old male diagnosed as human immunodeficiency virus positive, was on antiretroviral therapy, which consisted of 400 mg twice daily darunavir, 100 mg/day ritonavir, and 50 mg/day dolutegravir. He had been negative for human immunodeficiency virus RNA for the past 3 years. The patient developed renal insufficiency without any known cause and started hemodialysis. A living donor transplant from his son was performed, and the patient received ATG Fresenius-S (Neovii Biotech, Rapperswil, Switzerland) induction and a maintenance immunosuppression therapy consisting of methylprednisolone, mycophenolate mofetil, and tacrolimus. There were no incidences of delayed graft function or acute rejection. Because of tacrolimus and ritonavir interaction, tacrolimus trough levels were too high. With tacrolimus withdrawn, tacrolimus trough level decreased to detectable levels 2 weeks later. Antiretroviral therapy was continued on the same dosage. At month 4 posttransplant, the patient's creatinine level was 1.01 mg/dL. At present, the patient has had no complications and no episodes of rejection. Kidney transplant is the most favorable replacement therapy for HIV-positive patients who are under controlled AIDS care with highly active antiretroviral therapy. However, drug interactions should be carefully evaluated. Key words: HIV infection, Immunosuppression, Renal transplantation IntroductionThe introduction of highly active antiretroviral therapy has reduced the mortality and progression to acquired immunodeficiency syndrome (AIDS). However, end-stage renal disease can occur in patients who are human immunodeficiency virus (HIV) positive. A broad spectrum of diseases such as hypertension, diabetes mellitus, and glomerular diseases are the major causes of end-stage kidney disease. 1 Human immunodeficiency virus-associated nephropathy is a specific glomerular collapsing sclerosing disease seen in HIV-positive patients. 2 Whatever the cause, renal transplant is the optimal therapy for the HIV-positive population rather than dialysis modalities if some criteria are met. These criteria include undetectable plasma HIV RNA, CD4 cell count over 200 cells/μL, and the absence of any AIDS-defining illnesses. 3 Over time, the best immunosuppression modalities have become better known for this population of patients. However, drug interactions are still important points with immunosuppression therapy. Delayed graft function (DGF) and acute rejection are the most important issues to be noted carefully during the early posttransplant perio...

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“…Three liver transplant patients were on ritonavir-boosted PI therapy (1 on saquinavir 1,000 mg twice daily plus lopinavir 400/ritonavir 100 mg twice daily, 1 on fosamprenavir 700/100 mg twice daily, 1 on darunavir 600/ritonavir 100 mg twice daily), and received tacrolimus doses of 0.06, 0.03, and 0.08 mg daily, with median tacrolimus concentrations of 6.6, 3.0 and 7.9 ng/ mL, respectively. Two other patients began raltegravir-based cART while on tacrolimus 1 or 2 mg twice daily; no tacrolimus dose adjustment was needed and tacrolimus plasma concentrations were not altered [14].…”

Section: Transplant Drugsmentioning

confidence: 99%

Important Drug-Drug Interactions in HIV-Infected Persons on Antiretroviral Therapy: An Update on New Interactions Between HIV and Non-HIV Drugs

Tseng

Foisy²

2011

Curr Infect Dis Rep

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Advances in antiretroviral therapy have turned HIV into a chronic, manageable disease. Patients often require treatment for co-morbid conditions as well as HIV, and consequently, pharmacokinetic interactions between antiretrovirals (ARVs) and other drug classes are an increasing concern. Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are involved in the CYP450 or other transporter systems, and may be associated with higher risk of clinically significant drug interactions. One reverse transcriptase inhibitor, abacavir, has demonstrated weak inhibition of CYP3A4, 2D6 and 2C9 in vitro, but is not associated with any clinically significant interactions involving the CYP450 system. The integrase inhibitor raltegravir is not involved in the CYP450 system, and may be a suitable option to use when trying to minimize interactions with other drug classes. This review summarizes recently published data on clinically significant drug interactions between ARVs and other drug classes including antineoplastics, immunosuppressant transplant drugs, directly acting antivirals for hepatitis C, antifungals, antimalarials, corticosteroids, psychotropics, hormonal contraceptives, anticoagulants, drugs for pulmonary hypertension, and herbal products. In situations of suspected or potential interactions, close monitoring is warranted, and dose adjustments or substitutions may be required.

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Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir

Abstract: Decreasing the dose of tacrolimus to 0.03-0.08 mg daily in patients with concomitant boosted PI therapy resulted in stable tacrolimus blood levels without alteration of PI drug levels. Concomitant use of raltegravir and tacrolimus revealed no clinically relevant drug interaction.

Cited by 34 publications

References 18 publications

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

Kidney Transplant in a Human Immunodeficiency Virus-Positive Patient: Case Report of Drug Interactions

Important Drug-Drug Interactions in HIV-Infected Persons on Antiretroviral Therapy: An Update on New Interactions Between HIV and Non-HIV Drugs

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