Klibanov Olga M, Clark-Vetri Rachel
Department of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140-5101, USA.
Pharmacotherapy. 2007 Jan;27(1):122-36. doi: 10.1592/phco.27.1.122.
Although highly active antiretroviral therapy (HAART) has revolutionized the treatment of human immunodeficiency virus (HIV)-positive patients, malignancies in the setting of HIV infection remain an appreciable problem. We evaluated the changing epidemiology of HIV-related malignancies, optimal neoplastics and their effect on viral dynamics, and evidence regarding drug interactions between chemotherapy and antiretrovirals. A MEDLINE search (January 1966-June 2006) was performed to identify clinical trials, review articles, and meta-analyses; abstracts from HIV conferences were also searched. Survival of patients with HIV-related malignancies has substantially improved since the advent of HAART. Chemotherapy for malignancies in the HIV-positive population generally resembles that for the HIV-negative population, with trials revealing an elevated frequency of toxicities in HIV-positive patients. Studies of antineoplastics have shown no long-term adverse effects on viral dynamics in terms of immunologic or virologic HIV markers. Limited pharmacokinetic data with antineoplastics and antiretrovirals suggest possible changes in some pharmacokinetic parameters, but these results should be interpreted cautiously because of the small numbers of patients enrolled in the trials. Researchers also report an increased frequency of chemotherapy-related toxicities when HAART was coadministered with antineoplastics. This increase was likely due to impairment of cytochrome P450 metabolism of antineoplastics by protease inhibitors. Because of the survival benefits of HAART, the integration of antiretrovirals with chemotherapy is now preferred for patients with HIV-related malignancies. However, because the metabolic pathways of many of these agents are similar, the effectiveness of antineoplastic therapy and its related toxicities should be vigilantly monitored in this patient population.
尽管高效抗逆转录病毒疗法（HAART）彻底改变了人类免疫缺陷病毒（HIV）阳性患者的治疗方式，但HIV感染患者发生恶性肿瘤仍然是一个相当严重的问题。我们评估了HIV相关恶性肿瘤流行病学的变化、最佳的肿瘤治疗药物及其对病毒动力学的影响，以及关于化疗与抗逆转录病毒药物之间药物相互作用的证据。通过检索MEDLINE数据库（1966年1月至2006年6月）来识别临床试验、综述文章和荟萃分析；还检索了HIV会议的摘要。自HAART出现以来，HIV相关恶性肿瘤患者的生存率有了显著提高。HIV阳性人群中恶性肿瘤的化疗通常与HIV阴性人群相似，试验显示HIV阳性患者的毒性发生率更高。抗肿瘤药物研究表明，就HIV的免疫学或病毒学标志物而言，对病毒动力学没有长期不良影响。关于抗肿瘤药物和抗逆转录病毒药物的药代动力学数据有限，提示某些药代动力学参数可能发生变化，但由于纳入试验的患者数量较少，这些结果应谨慎解读。研究人员还报告说，HAART与抗肿瘤药物联合使用时，化疗相关毒性的发生率增加。这种增加可能是由于蛋白酶抑制剂对抗肿瘤药物细胞色素P450代谢的损害。由于HAART具有生存获益，对于HIV相关恶性肿瘤患者，现在倾向于将抗逆转录病毒药物与化疗联合使用。然而，由于这些药物中的许多药物代谢途径相似，在这一患者群体中应密切监测抗肿瘤治疗的有效性及其相关毒性。
