Department of Internal Medicine, Hôpital du Jura Bernois - Moutier, Rue Beausite 49, 2740, Moutier, Switzerland.
BMC Nephrol. 2019 Feb 26;20(1):69. doi: 10.1186/s12882-019-1257-6.
Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors and/or in the setting of other comorbidities. We discuss the mechanisms of these potential drug interactions as the cause of rhabdomyolysis and acute kidney injury in the context of prior and current medication therapy with possible underlying liver and kidney dysfunction.
We describe the case of a 54-year-old man diagnosed with HIV who developed severe rhabdomyolysis-induced anuric acute kidney injury (AKI) requiring renal replacement therapy following introduction of Genvoya® concomitantly with simvastatin, in the context of recently diagnosed hepatitis C and hepatitis A. Haemodialysis was continued over 5 weeks followed by progressive clinical and biological improvements. Five months later, a new antiretroviral regimen was started and has been well tolerated.
Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Patients receiving HMG-CoA reductase inhibitors should be monitored regularly for the occurrence of muscular adverse effects and drug interactions should be considered with each new prescription or change in clinical status. There are many online tools that enable clinicians to rapidly check for drug interactions. We recommend the one from the University of Liverpool for patients under HIV-therapy ( https://www.hiv-druginteractions.org/checker ), while for patients under hepatitis C-therapy, we advise to consult http://www.hep-druginteractions.org/ . This case illustrates the importance of multidisciplinary collaboration in the treatment of HIV-positive patients because of their complexity, associated comorbidities and the potential of multiple drug-drug interactions potentially exacerbated by underlying liver and/or kidney dysfunction.
Genvoya®（艾维雷格韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺）是一种最近用于治疗人类免疫缺陷病毒（HIV）的单一疗法。然而，由于其复杂性，难以预测药物相互作用，尤其是当与 HMG-CoA 还原酶抑制剂联合使用或存在其他合并症时。我们讨论了这些潜在药物相互作用的机制，这些机制导致了横纹肌溶解症和急性肾损伤，同时考虑了先前和当前的药物治疗，以及可能存在的肝肾功能障碍。
我们描述了一位 54 岁男性 HIV 感染者的病例，他在诊断为丙型肝炎和甲型肝炎后，同时使用辛伐他汀和 Genvoya®，导致严重的横纹肌溶解症引起的无尿急性肾损伤（AKI），需要肾脏替代治疗。血液透析持续了 5 周，随后临床和生物学情况逐渐改善。5 个月后，开始了新的抗逆转录病毒治疗方案，并且耐受良好。
辛伐他汀、洛伐他汀（由于其 CYP3A4 代谢），以及阿托伐他汀（仅部分通过 CYP3A4 代谢）等 HMG-CoA 还原酶抑制剂具有最大的药物相互作用风险，不应在 HIV 治疗患者中使用。接受 HMG-CoA 还原酶抑制剂治疗的患者应定期监测肌肉不良反应的发生，并且应在每次新处方或临床状况变化时考虑药物相互作用。有许多在线工具可以使临床医生快速检查药物相互作用。我们建议 HIV 治疗患者使用利物浦大学的在线工具（https://www.hiv-druginteractions.org/checker），而对于丙型肝炎治疗患者，建议咨询 http://www.hep-druginteractions.org/。这个病例说明了多学科合作在治疗 HIV 阳性患者中的重要性，因为他们的病情复杂，存在合并症，并且可能由于潜在的肝肾功能障碍而加剧多种药物-药物相互作用的风险。
