Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review
1 Department of Clinical Pharmacy, University Medical Center Utrecht , The Netherlands .AIDS patient care and STDs (Impact Factor: 3.5). 10/2012; 26(10):568-81. DOI: 10.1089/apc.2012.0169
Abstract 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drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients.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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- "Clinical experience indicates that patients on PI may require only 1e2 mg of TAC per week to keep therapeutic levels . Patients on a ritonavir-boosted PI regimen can require even lower doses of CNIs . In our experience the dose of TAC in patients with darunavir boosted by ritonavir (Table 2, patients 1 to 3) was 0.5 mg/d each 7e10 days. "
ABSTRACT: Introduction: Renal transplantation (RT) in patients infected with human immunodeficiency virus (HIV) has significantly improved under the advent of combined antiretroviral therapy (cART). The authors describe their experience in RT in patients with HIV from September 2010 to June 2013. Cases report: Four patients underwent transplantation (3 with HIV-1 and 1 with HIV-2), three patients were male, and one was black. None were coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV). Etiology of kidney disease was HIV-associated nephropathy (2 patients), immunoglobulin (Ig)A nephropathy, and unknown. Average age at RT was 51 (range, 41-63) years. No patient was of high immunologic risk. Immunosuppression consisted of basiliximab for induction and prednisolone, tacrolimus (TAC), and mycophenolate mofetil for maintenance. TAC levels varied considerably in the early days (8.5-46 ng/mL), requiring major adjustments in TAC dose. Only the HIV-2 patient had delayed graft function. The follow-up of patients with HIV-1 was 37, 19, and 16 months, and 3 months for the HIV-2 patient. CD4+ T cells decreased in the early days after transplantation with subsequent improvement, along with persistent virological suppression. In the HIV-1 group there were no major infectious, cardiovascular, or neoplastic complications. Nevertheless, the HIV-2 patient died 3 months after RT due to H1N1 pneumonia complicated by pulmonary aspergillosis. Average estimated (CKD- EPI) glomerular filtration rate (eGFR) at 6 months was 85.6 mL/min/1.73 m(2). Conclusion: Besides the difficulty in adjusting calcineurin inhibitors levels due to its interaction with antiretroviral therapy, namely with protease inhibitors, no patient had acute rejection. Furthermore, all patients presented an excellent control of viro-immunologic parameters. At the last follow-up neither cardiovascular events nor neoplastic complications were observed. Our results highlight the favorable outcome of RT in HIV-1-infected patients. The HIV-2 patient died due to severe infection, and the clinical management and potential benefit of RT in HIV-2-infected patients needs further study.Transplantation Proceedings 07/2014; 46(6):1718-22. DOI:10.1016/j.transproceed.2014.05.030 · 0.98 Impact Factor
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ABSTRACT: Liver transplantation (LT) is an accepted mode of treatment for patients with chronic liver disease. Historically, patients with HIV were excluded from LT programs, but with the introduction of highly effective antiretroviral regimens, HIV is no longer a contraindication. LT outcomes for some liver diseases in HIV-positive patients are equivalent to those observed in non-HIV-positive patients. This is not the case for patients coinfected with HIV and HCV, however, where results at 5 years have led to suggestions that LT for coinfection should be abandoned. This article examines the role of LT for HIV/HCV and identifies groups of patients where transplantation is associated with good outcomes. We believe that the application of existing knowledge to patient selection and organ allocation could improve outcomes further, and with the advent of directly acting antivirals for HCV, LT for HIV/HCV coinfection will no longer be controversial.Future Virology 07/2013; 8(7):639-648. DOI:10.2217/fvl.13.51 · 1.01 Impact Factor
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ABSTRACT: Combination antiretroviral therapy has resulted in longer life expectancies in persons living with HIV; however, end organ disease and death from organ failure have become growing issues for this population. With effective therapies for viral suppression, HIV is no longer considered an absolute contraindication to organ transplantation. Over the past decade, studies of transplantation in patients with HIV have had encouraging results such that patients with organ failure are pursuing transplantation. This review focuses on the current status of organ transplantation for HIV-infected persons.Current Infectious Disease Reports 10/2013; 15(6). DOI:10.1007/s11908-013-0381-x · 1.68 Impact Factor
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