Cattaneo Dario, Gervasoni Cristina
Unit of Clinical Pharmacology, Department of Laboratory Medicine, ASST Fatebenefratelli Sacco University Hospital, Via GB Grassi 74, 20157, Milan, Italy.
III Division of Infectious Diseases, Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy.
Eur J Drug Metab Pharmacokinet. 2017 Aug;42(4):559-572. doi: 10.1007/s13318-016-0394-6.
Highly active antiretroviral therapy (HAART) has dramatically increased the survival of HIV-infected patients from Western countries reducing the incidence of opportunistic infections and AIDS-related malignancies, and improving the patients' quality of life compared with the pre-HAART era. HIV is thus now considered in the West as a chronic disease, with the majority of HIV-infected patients successfully reaching an optimal immune and virological outcome a few months after starting HAART. However, this switch from acute to chronic disease has been accompanied by an increased incidence of chronic kidney disease (CKD), reported in up to 60% of HIV-infected patients. Tenofovir disoproxil fumarate (TDF) is considered to play a significant role in the development of CKD in these patients. It has been proposed that tenofovir alafenamide (TAF), a prodrug formulation able to providing lower systemic and renal drug exposure, could potentially contribute to reduce the development of CKD in HAART-treated patients. On the other hand, the pharmacokinetics of some components of HAART can be significantly altered in HIV-infected patients developing CKD. TDF- or TAF-based antiretroviral regimens should be avoided in patients with a creatinine clearance of less than 50 or 30 mL/min, respectively. This review focuses on the pharmacokinetic changes of novel antiretroviral drugs in HIV-infected patients with renal impairment or requiring renal replacement therapy, and provides some suggestions on how to change drug doses in these clinical settings.
高效抗逆转录病毒疗法（HAART）显著提高了西方国家HIV感染患者的生存率，降低了机会性感染和艾滋病相关恶性肿瘤的发生率，与HAART治疗前的时代相比，患者的生活质量也得到了改善。因此，在西方，HIV现在被视为一种慢性病，大多数HIV感染患者在开始HAART治疗几个月后就能成功达到最佳的免疫和病毒学结果。然而，这种从急性病到慢性病的转变伴随着慢性肾脏病（CKD）发病率的增加，在高达60%的HIV感染患者中都有报道。富马酸替诺福韦二吡呋酯（TDF）被认为在这些患者CKD的发生中起重要作用。有人提出，替诺福韦艾拉酚胺（TAF），一种能够降低全身和肾脏药物暴露的前药制剂，可能有助于减少接受HAART治疗患者中CKD的发生。另一方面，在发生CKD的HIV感染患者中，HAART某些成分的药代动力学可能会发生显著改变。肌酐清除率分别低于50或30 mL/min的患者应避免使用基于TDF或TAF的抗逆转录病毒治疗方案。本综述重点关注新型抗逆转录病毒药物在肾功能损害或需要肾脏替代治疗的HIV感染患者中的药代动力学变化，并就这些临床情况下如何调整药物剂量提供一些建议。
