Clinical Pharmacy Specialist in Internal Medicine/HIV; Clinical Associate Professor of Pharmacy, Virginia Commonwealth University Health System, Richmond, VA, USA.
Ann Pharmacother. 2010 Feb;44(2):377-82. doi: 10.1345/aph.1M370. Epub 2009 Dec 29.
To describe the antiretroviral management of a patient diagnosed simultaneously with HIV/AIDS and diffuse large B-cell lymphoma, focusing on the drug-drug interactions between highly active antiretroviral therapy (HAART) and concomitant cancer chemotherapy.
A 55-year-old white man was recently diagnosed with HIV/AIDS and presented 1 month later with complaints of nausea, vomiting, abdominal pain, double vision, right eye discomfort/swelling, and a 3.6-kg weight loss. An excisional biopsy of a right inguinal lymph node confirmed a new diagnosis of diffuse large B-cell lymphoma. HAART and a chemotherapeutic regimen, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with intrathecal methotrexate, was to be initiated. As the potential for multiple drug-drug interactions existed, raltegravir, abacavir, and lamivudine were chosen for the initial HAART regimen. The patient achieved and maintained an undetectable viral load throughout 6 CHOP cycles.
HAART improves the chemotherapeutic response in patients with HIV and lymphoma. Multiple drug-drug interactions are possible in patients who are to receive CHOP and HAART. Cyclophosphamide and vincristine are metabolized via the CYP3A4 isoenzyme. Protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors both inhibit and induce CYP3A4, with the potential for altered chemotherapeutic and cytotoxic effects. When PIs are combined with CHOP, mortality is reduced, but increased adverse effects are demonstrated. Raltegravir, an integrase inhibitor, is eliminated via glucuronidation and results in minimal drug-drug interactions. Raltegravir improves virologic and immunologic responses in HAART-naïve patients and thus would be a suitable alternative for preventing chemotherapeutic-HAART interactions.
There is limited information published regarding the potential for interactions between HAART and cancer chemotherapy. While further research is necessary, it is important for clinicians to consider the potential for drug-drug interactions when designing a HAART regimen concurrently with chemotherapy.
描述一名同时诊断出 HIV/AIDS 和弥漫性大 B 细胞淋巴瘤的患者的抗逆转录病毒治疗管理，重点关注高效抗逆转录病毒治疗（HAART）和同时进行的癌症化疗之间的药物相互作用。
一名 55 岁白人男性最近被诊断出 HIV/AIDS，并在 1 个月后出现恶心、呕吐、腹痛、复视、右眼不适/肿胀和 3.6 公斤体重减轻的症状。右侧腹股沟淋巴结的切除活检证实了弥漫性大 B 细胞淋巴瘤的新诊断。将启动 HAART 和包括环磷酰胺、多柔比星、长春新碱、泼尼松（CHOP）联合鞘内甲氨蝶呤的化疗方案。由于存在多种药物相互作用的可能性，选择拉替拉韦、阿巴卡韦和拉米夫定作为初始 HAART 方案。患者在 6 个 CHOP 周期中实现并维持了不可检测的病毒载量。
HAART 改善了 HIV 和淋巴瘤患者的化疗反应。接受 CHOP 和 HAART 的患者可能会发生多种药物相互作用。环磷酰胺和长春新碱通过 CYP3A4 同工酶代谢。蛋白酶抑制剂（PI）和非核苷类逆转录酶抑制剂均抑制和诱导 CYP3A4，具有改变化疗和细胞毒性作用的潜力。当 PI 与 CHOP 联合使用时，死亡率降低，但显示出更多的不良反应。整合酶抑制剂拉替拉韦通过葡萄糖醛酸化消除，导致药物相互作用最小。拉替拉韦改善了 HAART 初治患者的病毒学和免疫学反应，因此是预防化疗-HAART 相互作用的合适替代品。
关于 HAART 和癌症化疗之间相互作用的潜在性，发表的信息有限。虽然需要进一步研究，但临床医生在设计 HAART 方案的同时考虑药物相互作用的潜在性非常重要。
