Munthali Chigomezgo, Taegtmeyer Miriam, Garner Paul G, Lalloo David G, Squire S Bertel, Corbett Elizabeth L, Ford Nathan, MacPherson Peter
Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK;
Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK.
J Int AIDS Soc. 2014 Jun 12;17(1):18932. doi: 10.7448/IAS.17.1.18932. eCollection 2014.
The World Health Organization (WHO) recommends that HIV-positive adults with CD4 count ≤500 cells/mm(3) initiate antiretroviral therapy (ART). In many countries of sub-Saharan Africa, CD4 count is not widely available or consistently used and instead the WHO clinical staging system is used to determine ART eligibility. However, concerns have been raised regarding its discriminatory ability to identify patients eligible to start ART. We therefore reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART eligibility according to CD4 count thresholds for ART initiation.
We systematically searched PubMed and Global Health databases and conference abstracts using a comprehensive strategy for studies that compared the results of WHO clinical staging with CD4 count thresholds. Studies performed in sub-Saharan Africa and published in English between 1998 and 2013 were eligible for inclusion according to our predefined study protocol. Two authors independently extracted data and assessed methodological quality and risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Summary estimates of sensitivity and specificity were derived for each CD4 count threshold and hierarchical summary receiver operator characteristic curves were plotted.
Fifteen studies met the inclusion criteria, including 25,032 participants from 14 countries. Most studies assessed individuals attending ART clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a sensitivity of 60% (95% CI: 45-73%, Q=914.26, p<0.001) and specificity of 73% (95% CI: 60-83%, Q=1439.43, p<0.001) for a CD4 threshold of ≤200 cells/mm(3) (11 studies); sensitivity and specificity for a threshold of CD4 count ≤350 cells/mm(3) were 45% (95% CI: 26-66%, Q=1607.31, p<0.001) and 85% (95% CI: 69-93%, Q=896.70, p<0.001), respectively (six studies). For the threshold of CD4 count ≤500 cells/mm(3) sensitivity was 14% (95% CI: 13-15%) and specificity was 95% (95% CI: 94-96%) (one study).
When used for individual treatment decisions, WHO clinical staging misses a high proportion of individuals who are ART eligible by CD4 count, with sensitivity falling as CD4 count criteria rises. Access to accurate, accessible, robust and affordable CD4 count testing methods will be a pressing need for as long as ART initiation decisions are based on criteria other than seropositivity.
世界卫生组织（WHO）建议，CD4 细胞计数≤500 个/立方毫米的 HIV 阳性成年人应开始抗逆转录病毒治疗（ART）。在撒哈拉以南非洲的许多国家，CD4 细胞计数并未广泛可得或持续使用，而是使用 WHO 临床分期系统来确定 ART 治疗资格。然而，对于其识别符合开始 ART 治疗条件患者的鉴别能力，人们已提出担忧。因此，我们根据 ART 起始的 CD4 细胞计数阈值，回顾了 WHO 3 期或 4 期评估在识别 ART 治疗资格方面的准确性。
我们使用全面的检索策略，系统地检索了 PubMed 和全球卫生数据库以及会议摘要，以查找比较 WHO 临床分期结果与 CD4 细胞计数阈值的研究。根据我们预先定义的研究方案，1998 年至 2013 年间在撒哈拉以南非洲进行并以英文发表的研究符合纳入标准。两位作者独立提取数据，并使用诊断准确性研究质量评估工具（QUADAS - 2）评估方法学质量和偏倚风险。针对每个 CD4 细胞计数阈值得出敏感性和特异性的汇总估计值，并绘制分层汇总接受者操作特征曲线。
15 项研究符合纳入标准，包括来自 14 个国家的 25,032 名参与者。大多数研究评估了治疗开始前在 ART 诊所就诊的个体。对于 CD4 阈值≤200 个/立方毫米（11 项研究），WHO 临床 3 期或 4 期疾病的敏感性为 60%（95%CI：45 - 73%，Q = 914.26，p < 0.001），特异性为 73%（95%CI：60 - 83%，Q = 1439.43，p < 0.001）；对于 CD4 细胞计数≤350 个/立方毫米的阈值，敏感性和特异性分别为 45%（95%CI：26 - 66%，Q = 1607.31，p < 0.001）和 85%（95%CI：69 - 93%，Q = 896.70，p < 0.001）（6 项研究）。对于 CD4 细胞计数≤500 个/立方毫米的阈值，敏感性为 14%（95%CI：13 - 15%），特异性为 95%（95%CI：94 - 96%）（1 项研究）。
当用于个体治疗决策时，WHO 临床分期会遗漏很大一部分根据 CD4 细胞计数符合 ART 治疗资格的个体，且随着 CD4 细胞计数标准升高，敏感性下降。只要 ART 起始决策基于血清学阳性以外的标准，获取准确、可及、可靠且经济实惠的 CD4 细胞计数检测方法将是一项紧迫需求。
