Immunologic Criteria Are Poor Predictors of Virologic Outcome: Implications for HIV Treatment Monitoring in Resource-Limited Settings
Immunologic Criteria Are Poor Predictors of Virologic Outcome: Implications for HIV Treatment Monitoring in Resource-Limited Settings
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DOI：
10.1093/cid/cir729
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发表时间：
2011-12-15
影响因子：
11.8
通讯作者：
Kanki, Phyllis J.
中科院分区：
文献类型：
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作者：
Rawizza, Holly E.;Chaplin, Beth;Kanki, Phyllis J.
背景资料。病毒载量(VL)的量化被认为是决定资源丰富国家抗逆转录病毒治疗(ART)成功与否的关键。然而，在人类免疫缺陷病毒感染负担最大的资源有限的环境中，它并不广泛获得。在缺乏VL监测的情况下，切换到二线抗逆转录病毒治疗是基于世界卫生组织(WHO)的临床或免疫学失败标准。我们在尼日利亚的一个大型抗逆转录病毒治疗项目中评估了预测病毒学结果的CD4细胞标准的表现。实验室监测包括基线时的CD4细胞计数和VL，然后每6个月监测一次。失败被定义为在ART治疗至少6个月后连续2次VLS>；1000拷贝/毫升。病毒学结果与WHO定义的3个免疫失败标准进行比较。共有9690名患者被纳入分析(平均随访33.2个月)。共有1225名患者同时按免疫学和病毒学标准失败，872名患者仅按病毒学标准失败，1897名患者仅按免疫学标准失败。CD4细胞标准检测病毒失效的敏感性为58%，特异性为75%，阳性预测值为39%。对于病毒学和免疫学均失败的患者，VL标准确定失败的时间明显早于CD4细胞标准(中位数，10.4个月比15.6个月；P<；0.0001)。由于免疫学标准的低敏感性，大量的失败被遗漏，潜在地导致耐药突变的积累。此外，特异性和预测值很低，这可能导致大量不必要的ART切换。仅仅通过免疫学标准进行监测可能会导致成本增加，因为过度转向更昂贵的抗药治疗和抗药性病毒的开发。
Background. Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria.Methods. We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria.Results. A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001).Conclusions. Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.