Sangeda Raphael Z, Mosha Fausta, Prosperi Mattia, Aboud Said, Vercauteren Jurgen, Camacho Ricardo J, Lyamuya Eligius F, Van Wijngaerden Eric, Vandamme Anne-Mieke
Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
BMC Public Health. 2014 Oct 4;14:1035. doi: 10.1186/1471-2458-14-1035.
Optimal adherence to antiretroviral therapy is critical to prevent HIV drug resistance (HIVDR) epidemic. The objective of the study was to investigate the best performing adherence assessment method for predicting virological failure in resource-limited settings (RLS).
This study was a single-centre prospective cohort, enrolling 220 HIV-infected adult patients attending an HIV/AIDS Care and Treatment Centre in Dar es Salaam, Tanzania, in 2010. Pharmacy refill, self-report (via visual analog scale [VAS] and the Swiss HIV Cohort study-adherence questionnaire), pill count, and appointment keeping adherence measurements were taken. Univariate logistic regression (LR) was done to explore a cut-off that gives a better trade-off between sensitivity and specificity, and a higher area under the curve (AUC) based on receiver operating characteristic curve in predicting virological failure. Additionally, the adherence models were evaluated by fitting multivariate LR with stepwise functions, decision trees, and random forests models, assessing 10-fold multiple cross validation (MCV). Patient factors associated with virological failure were determined using LR.
Viral load measurements at baseline and one year after recruitment were available for 162 patients, of whom 55 (34%) had detectable viral load and 17 (10.5%) had immunological failure at one year after recruitment. The optimal cut-off points significantly predictive of virological failure were 95%, 80%, 95% and 90% for VAS, appointment keeping, pharmacy refill, and pill count adherence respectively. The AUC for these methods ranged from 0.52 to 0.61, with pharmacy refill giving the best performance at AUC 0.61. Multivariate logistic regression with boost stepwise MCV had higher AUC (0.64) compared to all univariate adherence models, except pharmacy refill adherence univariate model, which was comparable to the multivariate model (AUC = 0.64). Decision trees and random forests models were inferior to boost stepwise model. Pharmacy refill adherence (<95%) emerged as the best method for predicting virological failure. Other significant predictors in multivariate LR were having a baseline CD4 T lymphocytes count < 200 cells/μl, being unable to recall the diagnosis date, and a higher weight.
Pharmacy refill has the potential to predict virological failure and to identify patients to be considered for viral load monitoring and HIVDR testing in RLS.
最佳坚持抗逆转录病毒治疗对于预防艾滋病毒耐药性(HIVDR)流行至关重要。本研究的目的是调查在资源有限环境(RLS)中预测病毒学失败的最佳坚持评估方法。
本研究为单中心前瞻性队列研究,于2010年招募了220名在坦桑尼亚达累斯萨拉姆的一家艾滋病毒/艾滋病护理与治疗中心就诊的艾滋病毒感染成年患者。进行了药房配药记录、自我报告(通过视觉模拟量表[VAS]和瑞士艾滋病毒队列研究坚持问卷)、药丸计数以及就诊预约坚持测量。进行单变量逻辑回归(LR)以探索在敏感性和特异性之间能实现更好权衡且基于预测病毒学失败的受试者工作特征曲线具有更高曲线下面积(AUC)的临界值。此外,通过将多变量LR与逐步函数、决策树和随机森林模型拟合来评估坚持模型,评估10倍多重交叉验证(MCV)。使用LR确定与病毒学失败相关的患者因素。
162名患者有基线和招募后一年的病毒载量测量值,其中55名(34%)在招募后一年病毒载量可检测到,17名(10.5%)出现免疫失败。VAS、就诊预约、药房配药记录和药丸计数坚持分别显著预测病毒学失败的最佳临界值为95%、80%、95%和90%。这些方法的AUC范围为0.52至0.61,药房配药记录的表现最佳,AUC为0.61。与所有单变量坚持模型相比,带有逐步MCV的多变量逻辑回归的AUC更高(0.64),除了药房配药记录单变量模型,其与多变量模型相当(AUC = 0.64)。决策树和随机森林模型不如逐步模型。药房配药记录坚持(<95%)成为预测病毒学失败的最佳方法。多变量LR中的其他显著预测因素包括基线CD4 T淋巴细胞计数<200个细胞/μl、无法回忆起诊断日期以及体重较高。
药房配药记录有潜力预测病毒学失败,并识别在资源有限环境中应考虑进行病毒载量监测和艾滋病毒耐药性检测的患者。