Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA; Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA.
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Lancet HIV. 2019 Apr;6(4):e240-e249. doi: 10.1016/S2352-3018(18)30360-6. Epub 2019 Feb 27.
Research is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.
We studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.
Of 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months; <50 cells per μL vs ≥500 cells per μL, hazard ratio [HR] 3·2, 95% CI 2·2-4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ≥100 000 copies per mL vs ≤500 copies per mL, HR 9·6, 95% CI 6·5-14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per μL vs ≥500 cells per μL, HR 2·4, 95% CI 1·4-4·2; average viral load ≥100 000 copies per mL vs ≤500 copies per mL, HR 7·5, 95% CI 4·5-12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per μL vs ≥500 cells per μL, HR 426·3, 95% CI 58·1-3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100% vs 0%, HR 41·1, 95% CI 9·1-186·6).
Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma.
National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.
需要研究来更好地了解免疫抑制与 HIV 病毒血症以及非霍奇金淋巴瘤风险之间的关系，非霍奇金淋巴瘤是 HIV 感染者中常见的癌症。我们旨在确定非霍奇金淋巴瘤风险的关键 CD4 计数和 HIV RNA（病毒载量）预测因素，包括总体和亚型。
我们研究了 1996 年至 2014 年期间来自 21 个加拿大和美国队列的参与北美艾滋病队列合作研究和设计的 HIV 感染者。为了确定非霍奇金淋巴瘤风险的关键独立预测因素，我们评估了与最近、过去、累积和最低点或峰值 CD4 计数和病毒载量的时间更新相关的关联，使用人口统计学调整、队列分层 Cox 模型，并使用赤池信息量准则比较模型。
在研究期间，102131 名 HIV 感染者中有 712 人患上了非霍奇金淋巴瘤。总体非霍奇金淋巴瘤风险的关键独立预测因素是最近的 CD4 计数（即滞后 6 个月；<50 个细胞/μL 与≥500 个细胞/μL，风险比[HR]3.2，95%置信区间[CI]2.2-4.7）和滞后 6 个月的 3 年窗口期间的平均病毒载量（累积指标；≥100000 拷贝/毫升与≤500 拷贝/毫升，HR 9.6，95%CI 6.5-14.0）。这些指标也是弥漫性大 B 细胞淋巴瘤（最近的 CD4 计数<50 个细胞/μL 与≥500 个细胞/μL，HR 2.4，95%CI 1.4-4.2；平均病毒载量≥100000 拷贝/毫升与≤500 拷贝/毫升，HR 7.5，95%CI 4.5-12.7）风险的关键预测因素。然而，最近的 CD4 计数是 CNS 非霍奇金淋巴瘤风险的唯一关键预测因素（<50 个细胞/μL 与≥500 个细胞/μL，HR 426.3，95%CI 58.1-3126.4），3 年窗口期间病毒载量大于 500 拷贝/毫升的比例（累积指标）是 Burkitt 淋巴瘤的唯一关键预测因素（100%与 0%，HR 41.1，95%CI 9.1-186.6）。
近期免疫抑制和长期 HIV 病毒血症在非霍奇金淋巴瘤的发生中都具有重要的独立作用，可能存在亚型异质性。早期和持续的抗逆转录病毒治疗以降低 HIV 复制、抑制 B 细胞激活和恢复整体免疫功能对于预防非霍奇金淋巴瘤至关重要。
美国国立卫生研究院、疾病控制和预防中心、美国医疗保健研究和质量局、美国卫生资源和服务管理局、加拿大卫生研究所、安大略省卫生部和长期护理部以及艾伯塔省政府。
