Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS One. 2018 Jun 5;13(6):e0197665. doi: 10.1371/journal.pone.0197665. eCollection 2018.
Cancer causes significant morbidity and mortality among HIV patients in the US due to extended life expectancy with access to effective antiretroviral therapy. Low, detectable HIV RNA has been studied as a risk factor for adverse health outcomes, but its clinical impact on cancer risk remains unclear. The objective of this study was to determine whether HIV RNA <1,000 copies/mL six months after starting therapy was associated with 10-year first cancer risk.
We followed 7,515 HIV therapy initiators from a US-based multicenter clinical cohort from 1998 to 2014. We used nonparametric multiple imputation to account for viral loads that fell below assay detection limits, and categorized viral loads six months after therapy initiation into four groups: <20, 20-199, 200-999, and >999 copies/mL. We calculated estimates of the cumulative incidence of cancer diagnosis, accounting for death as a competing event. Inverse probability of exposure and censoring weights were used to control for confounding and differential loss to follow up, respectively.
Crude 10-year first cancer risk in the study sample was 7.03% (95% CI: 6.08%, 7.98%), with the highest risk observed among patients with viral loads between 200 and 999 copies/mL six months after ART initiation (10.7%). After controlling for baseline confounders, 10-year first cancer risk was 6.90% (95% CI: 5.69%, 8.12%), and was similar across viral load categories.
Overall risk of first cancer was not associated with incomplete viral suppression; however, cancer remains a significant threat to HIV patients after treatment initiation. As more HIV patients gain access to treatment in the current "treat all" era, occurrences of incomplete viral suppression will be observed more frequently in clinical practice, which supports continued study of the role of low-level HIV RNA on cancer development.
在美国，由于有效抗逆转录病毒疗法的应用，艾滋病毒感染者的预期寿命延长，因此癌症导致大量发病率和死亡率。已经研究了低水平、可检测到的 HIV RNA 作为不良健康结局的危险因素，但它对癌症风险的临床影响仍不清楚。本研究的目的是确定治疗开始后六个月 HIV RNA<1000 拷贝/ml 是否与 10 年首次癌症风险相关。
我们对来自美国多中心临床队列的 7515 名 HIV 治疗初治者进行了随访，从 1998 年到 2014 年。我们使用非参数多次插补法来解释低于检测限的病毒载量，并将治疗开始后六个月的病毒载量分为四组：<20、20-199、200-999 和>999 拷贝/ml。我们计算了癌症诊断累积发生率的估计值，将死亡作为竞争事件进行了考虑。分别使用暴露的逆概率和删失权重来控制混杂因素和随访差异的丢失。
研究样本的粗 10 年首次癌症风险为 7.03%（95%CI：6.08%，7.98%），其中在开始 ART 后六个月病毒载量在 200-999 拷贝/ml 之间的患者风险最高（10.7%）。在控制了基线混杂因素后，10 年首次癌症风险为 6.90%（95%CI：5.69%，8.12%），并且在不同病毒载量组之间相似。
总体而言，首次癌症的风险与不完全病毒抑制无关；然而，癌症仍然是治疗后 HIV 患者的一个重大威胁。随着越来越多的 HIV 患者在当前的“治疗所有”时代获得治疗，在临床实践中更频繁地观察到不完全病毒抑制的发生，这支持继续研究低水平 HIV RNA 对癌症发展的作用。
