免疫缺陷、HIV 病毒载量和抗逆转录病毒治疗对个体恶性肿瘤风险的影响（FHDH-ANRS CO4）：一项前瞻性队列研究。

Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study.

机构信息

INSERM U943 and UPMC UMR-S-943, Paris, France.

出版信息

Lancet Oncol. 2009 Dec;10(12):1152-9. doi: 10.1016/S1470-2045(09)70282-7. Epub 2009 Oct 7.

DOI:10.1016/S1470-2045(09)70282-7

PMID:19818686

Abstract

BACKGROUND

The relative roles of immunodeficiency, HIV viral load, and combination antiretroviral therapy (cART) in the onset of individual cancers have rarely been examined. We examined the effect of these factors on the risk of specific cancers in patients infected with HIV-1.

METHODS

We investigated the incidence of both AIDS-defining cancers (Kaposi's sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers (Hodgkin's lymphoma, lung cancer, liver cancer, and anal cancer) in 52 278 patients followed up in the French Hospital Database on HIV cohort during 1998-2006 (median follow-up 4.9 years, IQR 2.1-7.9; 255 353 person-years). We tested 78 models with different classifications of immunodeficiency, viral load, and cART with Poisson regression.

FINDINGS

Current CD4 cell count was the most predictive risk factor for all malignancies apart from anal cancer. Compared with patients with CD4 count greater than 500 cells per microL, rate ratios (RR) ranged from 1.9 (95% CI 1.3-2.7) for CD4 counts 350-499 cells per microL to 25.2 (17.1-37.0) for counts less than 50 cells per microL for Kaposi's sarcoma (p<0.0001), from 1.3 (0.9-2.0) to 14.8 (9.7-22.6) for non-Hodgkin lymphoma (p<0.0001), from 1.2 (0.7-2.2) to 5.4 (2.4-12.1) for Hodgkin's lymphoma (p<0.0001), from 2.2 (1.3-3.6) to 8.5 (4.3-16.7) for lung cancer (p<0.0001), and from 2.0 (0.9-4.5) to 7.6 (2.7-20.8) for liver cancer (p<0.0001). For cervical cancer, we noted a strong effect of current CD4 (RR 0.7 per log(2), 95% CI 0.6-0.8; p=0.0002). The risk of Kaposi's sarcoma and non-Hodgkin lymphoma increased for current plasma HIV RNA greater than 100 000 copies per mL compared with patients with controlled viral load (RR 3.1, 95% CI 2.3-4.2, p<0.0001; and 2.9, 2.1-3.9, p<0.0001, respectively), whereas cART was independently associated with a decreased incidence (0.3, 0.2-0.4, p<0.0001; and 0.8, 0.6-1.0, p=0.07, respectively). The RR of cervical cancer for those receiving cART was 0.5 (0.3-0.9; p=0.03). The risk of anal cancer increased with the time during which the CD4 count was less than 200 cells per microL (1.3 per year, 1.2-1.5; p=0.0001), and viral load was greater than 100 000 copies per mL (1.2 per year, 1.1-1.4, p=0.005).

INTERPRETATION

cART would be most beneficial if it restores or maintains CD4 count above 500 cells per microL, thereby indicating an earlier diagnosis of HIV infection and an earlier treatment initiation. Cancer-specific screening programmes need to be assessed in patients with HIV.

FUNDING

Agence Nationale de Recherches sur le SIDA et les hépatites (ANRS), INSERM, and the French Ministry of Health.

摘要

背景

免疫缺陷、HIV 病毒载量和联合抗逆转录病毒疗法（cART）在个体癌症发病中的相对作用很少被研究。我们研究了这些因素对感染 HIV-1 的患者特定癌症风险的影响。

方法

我们调查了在 1998-2006 年期间在法国医院艾滋病毒队列数据库中随访的 52278 例患者的艾滋病定义癌症（卡波西肉瘤、非霍奇金淋巴瘤和宫颈癌）和非艾滋病定义癌症（霍奇金淋巴瘤、肺癌、肝癌和肛门癌）的发病率。我们用泊松回归检验了 78 种不同免疫缺陷、病毒载量和 cART 分类的模型。

结果

除肛门癌外，目前的 CD4 细胞计数是所有恶性肿瘤的最具预测性的危险因素。与 CD4 计数大于 500 个细胞/μL 的患者相比，CD4 计数为 350-499 个细胞/μL 的比值比（RR）范围为 1.9（95%CI 1.3-2.7），CD4 计数小于 50 个细胞/μL 的比值比为 25.2（17.1-37.0），Kaposi 肉瘤（p<0.0001），非霍奇金淋巴瘤（p<0.0001）为 1.3（0.9-2.0）至 14.8（9.7-22.6），霍奇金淋巴瘤（p<0.0001）为 1.2（0.7-2.2）至 5.4（2.4-12.1），肺癌（p<0.0001）为 2.2（1.3-3.6）至 8.5（4.3-16.7），肝癌（p<0.0001）为 2.0（0.9-4.5）至 7.6（2.7-20.8）。对于宫颈癌，我们发现当前 CD4 计数有很强的影响（每对数 0.7，95%CI 0.6-0.8；p=0.0002）。与病毒载量得到控制的患者相比，当前血浆 HIV RNA 大于 100000 拷贝/毫升的 Kaposi 肉瘤和非霍奇金淋巴瘤的风险增加（RR 3.1，95%CI 2.3-4.2，p<0.0001；和 2.9，2.1-3.9，p<0.0001），而 cART 与发病率降低独立相关（0.3，0.2-0.4，p<0.0001；和 0.8，0.6-1.0，p=0.07）。接受 cART 的宫颈癌患者的 RR 为 0.5（0.3-0.9；p=0.03）。肛门癌的风险随着 CD4 计数小于 200 个细胞/μL 的时间而增加（每年增加 1.3，1.2-1.5；p=0.0001），病毒载量大于 100000 拷贝/毫升（每年增加 1.2，1.1-1.4，p=0.005）。