Association of immunosuppression and HIV viremia with anal cancer risk in persons living with HIV in the United States and Canada.

BACKGROUND People living with HIV (PLWH) have a markedly elevated anal cancer risk largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. METHODS We studied 102,777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures calculated within pre-specified moving time windows. We compared models using the Akaike's information criterion. RESULTS Cumulative and nadir/peak CD4 or HIV RNA measures from ~8.5 to ~4.5 years in the past were generally better predictors for anal cancer risk than their corresponding measures from ~4.5 years to ~6 months in the past. However, the best model included CD4 nadir (i.e., the lowest CD4) from ~8.5 years to ~6 months in the past (hazard ratio for <50 vs. ≥500 cells/µL: 13.4; 95% confidence interval: 3.5-51.0) and proportion of time CD4 <200 cells/µL from ~8.5 to ~4.5 years in the past (a cumulative measure; hazard ratio for 100% vs. 0% of time: 3.1; 95% confidence interval: 1.5-6.6). CONCLUSIONS Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

背景 艾滋病病毒感染者（PLWH）患肛门癌的风险显著升高，这主要是由于对致癌的人乳头瘤病毒感染的免疫调节控制丧失。为了更好地理解肛门癌的发生和预防，我们确定近期、过去、累积的或最低值/峰值的CD4 + T细胞计数（CD4）和/或艾滋病病毒 - 1 RNA水平（HIV RNA）是否能最好地预测肛门癌风险。 方法 我们对1996 - 2014年期间来自参与北美艾滋病队列协作研究与设计的21个队列的102,777名艾滋病病毒感染者进行了研究。使用经人口统计学调整的、队列分层的考克斯模型，我们评估了肛门癌风险与各种随时间更新的CD4和HIV RNA指标之间的关联，包括在预先指定的移动时间窗口内计算的累积指标和最低值/峰值指标。我们使用赤池信息准则比较了模型。 结果 过去约8.5年到约4.5年的累积和最低值/峰值CD4或HIV RNA指标通常比过去约4.5年到约6个月的相应指标能更好地预测肛门癌风险。然而，最佳模型包括过去约8.5年到约6个月的CD4最低值（即最低的CD4）（<50与≥500细胞/微升的风险比：13.4；95%置信区间：3.5 - 51.0）以及过去约8.5年到约4.5年CD4 <200细胞/微升的时间比例（一种累积指标；100%与0%时间的风险比：3.1；95%置信区间：1.5 - 6.6）。 结论 我们的结果与严重、长期的艾滋病病毒诱导的免疫抑制促进肛门癌发生是一致的。最低值和累积CD4可能是识别肛门癌高风险艾滋病病毒感染者的有用标志物。