Balinda Sheila N, Ondoa Pascale, Obuku Ekwaro A, Kliphuis Aletta, Egau Isaac, Bronze Michelle, Kasambula Lordwin, Schuurman Rob, Spieker Nicole, Rinke de Wit Tobias F, Kityo Cissy
Joint Clinical Research Center, P.O. Box 10005, Kampala, Uganda.
Amsterdam Institute for Global Health and Development, Department of Global Health, Academic medical Center, Trinity C Building, Pietersbergweg 17, 1105 BM, Amsterdam, the Netherlands.
PLoS One. 2016 Jan 29;11(1):e0145110. doi: 10.1371/journal.pone.0145110. eCollection 2016.
WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda.
We conducted a cross-sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml).
496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%-87.1%), 93% specificity (95% CI: 89.7%-96.4%), 89.3% accuracy (95% CI: 85%-92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively.
VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV-1 treatment in RLS.
世界卫生组织建议对接受抗逆转录病毒治疗（ART）的患者进行定期病毒载量（VL）监测，以便及时发现病毒学失败、预防获得性HIV耐药（HIVDR）并避免不必要地更换为二线ART。然而，在大多数资源有限的环境（RLS）中，常规VL检测的成本和复杂性仍然过高。我们在乌干达的三个临床环境中评估了一种简单、低成本的定性病毒失败检测方法（VFA），用于检测干血斑（DBS）中的病毒情况。
我们在乌干达联合临床研究中心的三个HIV/AIDS治疗中心进行了一项横断面诊断准确性研究。VFA采用从LTR基因扩增的HIV-1 RNA的半定量检测方法。我们将配对的干血斑（DBS）和血浆样本与COBAS AmpliPrep/COBAS TaqMan罗氏2版（VLref）作为参考检测方法进行比较。我们在两个病毒载量阈值（>5000或>1000拷贝/毫升）下使用VFA。
共有496对VFA和VLref结果可供比较分析。总体而言，与VLref相比，VFA的灵敏度为78.4%（95%可信区间：69.7%-87.1%），特异性为93%（95%可信区间：89.7%-96.4%），准确性为89.3%（95%可信区间：85%-92%），一致性kappa值为0.72。接受ART超过12个月患者的阳性和阴性预测值分别为72.7%和99.3%。
VFA能够正确分类89% 的病毒学失败情况。只有11% 的患者被错误分类，存在不必要或延迟更换为二线ART 的可能性。我们的研究结果为在资源有限的环境中推广简单且经济实惠的HIV-1治疗VL监测提供了机会。
