Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America ; Houston Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America.
PLoS One. 2013 Oct 2;8(10):e77409. doi: 10.1371/journal.pone.0077409. eCollection 2013.
The incidence of Hodgkin lymphoma (HL) has increased since introduction of combined antiretroviral therapy (cART). While HIV-related HL is highly associated with EBV, the causes underlying the rising incidence remain unclear. The aim of this study was to evaluate the effect of immune reconstitution on HL incidence among a cohort of HIV-infected male veterans ever receiving cART.
We performed a retrospective cohort study utilizing data from the Veterans Affairs HIV Clinical Case Registry from 1985-2010. HL cases were identified using ICD-9 codes (201.4-9). Poisson regression was conducted to evaluate relationships between cART-related immunologic measures (e.g., nadir CD4 before cART, time-updated CD4, % time undetectable HIV RNA) and HL incidence. Additionally, we examined CD4 change after cART initiation.
31,056 cART users contributed 287,256 person-years and 196 HL cases (IR=6.8/10,000 person-years). Rate of CD4 increase after cART was worse among HL cases than non-cases (p<0.05). In multivariate regression, HL risk was elevated among veterans with recent CD4 200-350 cells/µL (IRR=1.67, 95%CI=1.16-2.40) and <200 cells/µL (IRR=1.61, 95%CI=1.09-2.39), compared to >350 cells/µL. HL risk was lower among veterans with >80% time undetectable HIV RNA (IRR=0.57, 95%CI=0.35-0.92) and 40-80% undetectable (IRR=0.68, 95%CI=0.47-0.99), compared to <40% undetectable. HL risk was higher in the first 12 months (IRR=2.02, 95%CI=1.32-3.10) and 12-24 months (IRR=1.75, 95%CI=1.16-2.64) after cART initiation, compared to >36 months.
These data highlight immunosuppression and poor viral control may increase HL risk, specifically during immune reconstitution in the interval post cART initiation. Findings suggest an immune reconstitution type mechanism in HIV-related HL development.
自联合抗逆转录病毒疗法（cART）问世以来，霍奇金淋巴瘤（HL）的发病率有所增加。虽然 HIV 相关 HL 与 EBV 高度相关，但发病率上升的原因仍不清楚。本研究旨在评估在接受 cART 的 HIV 感染男性退伍军人队列中，免疫重建对 HL 发病率的影响。
我们利用 1985-2010 年退伍军人事务部 HIV 临床病例登记处的数据进行了回顾性队列研究。使用 ICD-9 代码（201.4-9）识别 HL 病例。使用泊松回归评估 cART 相关免疫指标（例如，cART 前的最低 CD4、时间更新的 CD4、HIV RNA 不可检测时间的百分比）与 HL 发病率之间的关系。此外，我们还检查了 cART 启动后 CD4 的变化。
31,056 名接受 cART 的患者共提供了 287,256 人年和 196 例 HL 病例（发病率为 6.8/1,000 人年）。与非病例相比，cART 后 CD4 增加的速度在 HL 病例中更差（p<0.05）。在多变量回归中，与 >350 个细胞/µL 的 CD4 相比，最近 CD4 为 200-350 个细胞/µL（IRR=1.67，95%CI=1.16-2.40）和 <200 个细胞/µL（IRR=1.61，95%CI=1.09-2.39）的退伍军人发生 HL 的风险更高。与 <40%不可检测相比，HIV RNA 不可检测时间 >80%（IRR=0.57，95%CI=0.35-0.92）和 40-80%（IRR=0.68，95%CI=0.47-0.99）的退伍军人发生 HL 的风险较低。与 >36 个月相比，cART 后 12 个月（IRR=2.02，95%CI=1.32-3.10）和 12-24 个月（IRR=1.75，95%CI=1.16-2.64）发生 HL 的风险更高。
这些数据突出了免疫抑制和病毒控制不佳可能会增加 HL 的风险，特别是在 cART 启动后免疫重建的间隔期间。研究结果表明，HIV 相关 HL 发展中存在免疫重建型机制。
