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基于药代遗传学特征的HIV感染癌症患者高效抗逆转录病毒疗法与抗白血病化疗之间的药物相互作用

Drug-Drug Interactions Based on Pharmacogenetic Profile between Highly Active Antiretroviral Therapy and Antiblastic Chemotherapy in Cancer Patients with HIV Infection.

作者信息

Berretta Massimiliano, Caraglia Michele, Martellotta Ferdinando, Zappavigna Silvia, Lombardi Angela, Fierro Carla, Atripaldi Luigi, Muto Tommaso, Valente Daniela, De Paoli Paolo, Tirelli Umberto, Di Francia Raffaele

机构信息

Department of Medical Oncology, CRO National Cancer Institute Aviano, Italy.

Department of Biochemistry, Biophysics and General Pathology, Second University of Naples Naples, Italy.

出版信息

Front Pharmacol. 2016 Mar 30;7:71. doi: 10.3389/fphar.2016.00071. eCollection 2016.

Abstract

The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the natural approach of HIV-related cancers. Several studies have shown that intensive antiblastic chemotherapy (AC) is feasible in HIV-infected patients with cancer, and that the outcome is similar to that of HIV-negative patients receiving the same AC regimens. However, the concomitant use of HAART and AC can result in drug accumulation or possible toxicity with consequent decreased efficacy of one or both classes of drugs. In fact, many AC agents are preferentially metabolized by CYP450 and drug-drug interactions (DDIs) with HAART are common. Therefore, it is important that HIV patients with cancer in HAART receiving AC treatment at the same time receive an individualized cancer management plan based on their liver and renal functions, their level of bone marrow suppression, their mitochondrial dysfunction, and their genotype profile. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, in order to maximize the efficacy of antiblastic therapy and minimize the risk of drug-drug interaction, a useful list of pharmacogenomic markers is provided.

摘要

高效抗逆转录病毒疗法(HAART)引入临床实践后,极大地改变了与HIV相关癌症的自然病程。多项研究表明,强化抗白血病化疗(AC)对于感染HIV的癌症患者是可行的,且其治疗结果与接受相同AC方案的HIV阴性患者相似。然而,同时使用HAART和AC可能会导致药物蓄积或潜在毒性,进而降低其中一类或两类药物的疗效。事实上,许多AC药物优先通过细胞色素P450代谢,与HAART的药物相互作用(DDIs)很常见。因此,对于正在接受HAART且同时接受AC治疗的HIV癌症患者,根据其肝肾功能、骨髓抑制水平、线粒体功能障碍及基因型谱制定个体化的癌症管理计划非常重要。本综述的目的是总结现有关于HAART对HIV/AIDS癌症患者临床管理的影响以及抗逆转录病毒药物与AC之间药物相互作用的数据。此外,为了使抗白血病治疗的疗效最大化并降低药物相互作用风险,还提供了一份有用的药物基因组学标志物清单。

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