Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk.
Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk.
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DOI：
10.1097/coh.0000000000000025
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发表时间：
2014-01
影响因子：
4.1
通讯作者：
Silverberg MJ
中科院分区：
文献类型：
--
作者：
Borges AH;Dubrow R;Silverberg MJ
批判性评价最近发表的关于HIV感染者中可能受联合抗逆转录病毒治疗（cART）影响的癌症风险相关因素的文献，以及早期cART启动降低该风险的潜力。导致非艾滋病定义的恶性肿瘤（NADM）的风险增加的因素尤其仍然知之甚少。免疫缺陷似乎是关键，而新出现的证据表明，HIV的直接促癌作用、激活的炎症和凝血途径以及cART毒性也可能起作用。通过减少HIV复制、改善免疫功能和限制慢性炎症，在较高的CD4+细胞计数下启动cART可能因此降低NADM风险。然而，cART只能部分地使HIV感染期间观察到的增强的炎症和凝血正常化，并且已经报道了关于cART是否（以及如何）影响NADM风险的相互矛盾的实验室和流行病学数据。此外，比较早期与延迟cART启动的随机对照试验的次要分析不确定。持续的流行病学监测是必要的，以监测HIV感染者中癌症发病率的趋势，并更好地了解早期cART对NADM风险的影响。辅助抗炎或抗血栓治疗在降低癌症风险方面的作用值得进一步研究。
To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk. Factors leading to increased risk of non-AIDS defining malignancies (NADM) in particular remain poorly understood. Immunodeficiency appears to be key, whereas evidence is emerging that a direct pro-oncogenic effect of HIV, activated inflammatory and coagulation pathways, and cART toxicity may also contribute. By reducing HIV replication, improving immune function and limiting chronic inflammation, cART initiation at higher CD4+ cell counts may therefore reduce NADM risk. However, cART only partly normalizes enhanced inflammation and coagulation seen during HIV infection and conflicting laboratory and epidemiological data have been reported as to if (and how) cART affects NADM risk. Furthermore, secondary analyses of randomized controlled trials comparing early versus delayed cART initiation were inconclusive. Continuous epidemiological surveillance is warranted to monitor trends in cancer incidence among HIV-infected individuals and to better understand the impact of earlier cART on NADM risk. The role of adjuvant anti-inflammatory or anti-thrombotic therapies to reduce cancer risk deserves further investigation.