Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
Clin Infect Dis. 2020 Mar 3;70(6):1176-1185. doi: 10.1093/cid/ciz329.
People living with human immunodeficiency virus (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.
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 during prespecified moving time windows. We compared models using the Akaike information criterion.
Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6).
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.
人类免疫缺陷病毒（HIV；PLWH）感染者的肛门癌风险显著升高，这主要是由于对致癌性人乳头瘤病毒感染的免疫调节控制丧失所致。为了更好地了解肛门癌的发展和预防，我们确定最近、过去、累计或最低/最高 CD4+T 细胞计数（CD4）和/或 HIV-1 RNA 水平（HIV RNA）是否能最好地预测肛门癌风险。
我们研究了 1996-2014 年间来自 21 个参与北美艾滋病队列合作研究和设计的队列的 102777 名 PLWH。使用人口统计学调整、队列分层 Cox 模型，我们评估了各种时间更新的 CD4 和 HIV RNA 指标与肛门癌风险之间的关联，包括在预先指定的移动时间窗口内的累计和最低/最高指标。我们使用赤池信息量准则比较模型。
过去约 8.5 至 4.5 年的累计和最低/最高 CD4 或 HIV RNA 指标通常是肛门癌风险的更好预测指标，而其相应的最近指标则不然。然而，最佳模型包括过去约 8.5 年至 6 个月的 CD4 最低值（即最低 CD4）（CD4<50 与≥500 个/µL 的危险比[HR]，13.4；95%置信区间[CI]，3.5-51.0）和过去约 8.5 至 4.5 年 CD4<200 个/µL 的时间比例（累计指标；HR 为 100%比 0%，3.1；95%CI，1.5-6.6）。
我们的结果与严重、长期 HIV 诱导的免疫抑制促进肛门癌一致。最低和累计 CD4 可能是识别肛门癌风险较高的 PLWH 的有用标志物。
