Kantor Rami, Diero Lameck, Delong Allison, Kamle Lydia, Muyonga Sarah, Mambo Fidelis, Walumbe Eunice, Emonyi Wilfred, Chan Philip, Carter E Jane, Hogan Joseph, Buziba Nathan
Division of Infectious Diseases, Brown University, Providence, Rhode Island, USA.
Clin Infect Dis. 2009 Aug 1;49(3):454-62. doi: 10.1086/600396.
The monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity, mortality, and drug resistance. Misclassification of failure may result in premature switching to second-line therapy.
Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing immunological failure (ie, their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cell percentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease).
There were 149 patients who were treated for 23 months; they were identified as having a 25% decrease in CD4 cell count (from 375 to 216 cells/microL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients, 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50% decrease in CD4 cell count, 18 (43%) were misclassified. In multivariate logistic regression, misclassification odds were associated with a higher CD4 cell count, a shorter duration of therapy, and a smaller CD4% percent decrease. By combining these variables, we may be able to improve our ability to predict treatment failure.
Immunological monitoring as a sole indicator of virological failure would lead to a premature switch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell count and for 43% patients who experience a 50% decrease in CD4 cell count, and therefore this type of monitoring should be reevaluated. Selective virological monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya, and should be considered in all resource-limited settings.
在资源有限的环境中，对接受抗逆转录病毒药物治疗的人类免疫缺陷病毒（HIV）感染患者的监测通常采用临床和免疫学标准。早期识别一线抗逆转录病毒治疗失败对于预防发病、死亡和耐药性至关重要。治疗失败的错误分类可能导致过早切换到二线治疗。
肯尼亚西部的成年患者，如果坚持一线治疗超过6个月且怀疑出现免疫失败（即其CD4细胞计数在6个月内下降25%），则测定其病毒载量（VL）。治疗失败的错误分类定义为CD4细胞计数下降25%且VL<400拷贝/mL。逻辑回归和树回归分析了VL与4个变量之间的关系：CD4 T细胞计数（以下简称CD4细胞计数）、表达CD4的T细胞百分比（以下简称CD4细胞百分比）、CD4 T细胞计数的下降百分比（以下简称CD4细胞计数下降百分比）以及表达CD4的T细胞百分比的下降百分比（以下简称CD4%下降百分比）。
149例患者接受了23个月的治疗；他们被确定为CD4细胞计数下降25%（从375个细胞/微升降至216个细胞/微升）且CD4%下降（从19%降至15%）；在这149例患者中，86例（58%）被错误分类为经历了治疗失败。在CD4细胞计数下降50%的42例患者中，18例（43%）被错误分类。在多变量逻辑回归中，错误分类的几率与较高的CD4细胞计数、较短的治疗持续时间以及较小的CD4%下降百分比相关。通过综合这些变量，我们或许能够提高预测治疗失败的能力。
将免疫监测作为病毒学失败的唯一指标，会导致58%的CD4细胞计数下降25%的患者和43%的CD4细胞计数下降50%的患者过早切换到有价值的二线治疗方案，因此这种监测方式应重新评估。选择性病毒学监测以及增加如CD4%下降趋势和治疗持续时间等指标，可能会系统地改善治疗失败的识别。在肯尼亚西部获得医疗服务学术模式（AMPATH）内，现在对于怀疑经历一线治疗失败的患者，VL检测是强制性的，并且在所有资源有限的环境中都应予以考虑。
