程序性死亡蛋白-1单克隆抗体治疗艾滋病合并恶性肿瘤的可行性分析

Feasibility of programmed death-1 monoclonal antibody treatment for patients with acquired immunodeficiency syndrome complicated with malignant tumor

目的探讨程序性死亡蛋白-1(programmed death-1,PD-1)抑制剂在艾滋病合并恶性肿瘤患者中的可行性、疗效和不良反应。方法纳入2020年9月至2021年8月于武汉大学中南医院使用PD-1单克隆抗体的艾滋病合并恶性肿瘤患者,收集患者基本情况、实验室检查结果、CD4^(+)T细胞计数、人类免疫缺陷病毒(human immunodeficiency virus,HIV)载量。PD-1单克隆抗体持续用药直至疾病进展或出现不可耐受的毒性反应,记录治疗期间患者的不良反应,每12周评估1次疗效。在治疗后每周检测1次HIV载量,连续4次,随后每4周1次,连续2次,其后每12周1次动态监测。结果共10例患者纳入研究,其中男7例,女3例;霍奇金淋巴瘤3例,宫颈癌和肝细胞癌各2例,非霍奇金淋巴瘤、非小细胞肺癌和肛门癌各1例。治疗前4例患者CD4^(+)T细胞计数为100~200/μL,2例CD4^(+)T细胞计数<100/μL。所有患者均至少完成3个周期PD-1单克隆抗体治疗,HIV载量均<20拷贝/mL。3例患者完全缓解,3例患者部分缓解。7例患者发生皮肤毛细血管增生症,3例发生大出血,1例发生听力障碍。结论PD-1抑制剂对HIV载量持续抑制无不良影响,且对肿瘤控制可发挥有效作用,可用于艾滋病合并肿瘤患者的治疗。但因其不良反应较多,故需多学科合作以降低合并症出现风险及处理严重并发症。

Objective To investigate the feasibility,efficacy and adverse reactions of programmed death-1(PD-1)inhibitors in patients with acquired immunodeficiency syndrome(AIDS)complicated with malignant tumor.Methods From September 2020 to August 2021,patients with AIDS complicated with malignant tumor in Zhongnan Hospital of Wuhan University were enrolled.Data including basic information,laboratory test results,CD4^(+)T cell count,human immunodeficiency virus(HIV)viral load were collected.Patients were continuously administered intravenously PD-1 monoclonal antibody until disease progression or intolerant toxicity reaction occurred.Adverse reactions during treatment were recorded.And treatment outcomes were assessed once every 12 weeks after treatment.HIV viral load was measured after treatment once a week for four consecutive times,then once four weeks for two consecutive times,and then once every 12 weeks.Results Ten patients were included in the study,including seven males and three females,three cases of Hodgkin′s lymphoma,two cases of cervical cancer and hepatocellular carcinoma respectively,one case of non-Hodgkin′s lymphoma,non-small cell lung cancer and anal cancer respectively.There were four patients with CD4^(+)T cell count of 100 to 200 cells/μL and two patients with CD4^(+)T cell count lower than 100 cells/μL.All patients had completed at least three cycles of treatment with PD-1 monoclonal antibody,HIV viral load remained lower than 20 copies/mL.Three cases achieved complete response and three cases achieved partial response.Adverse reactions were cutaneous capillary endothelial proliferation(CCEP)(seven cases),major bleeding(three cases),and hearing impairment(one case).Conclusions PD-1 inhibitor has no adverse effect on the continuous suppression of HIV viral load and has an effect on tumor control,so it is a viable choice in AIDS patients complicated with tumor.However,due to its considerable adverse reactions,multidisciplinary cooperation is needed to reduce the risk of complications and deal with serious complications.