Division of Medical Virology, Department of Pathology, NHLS Tygerberg and Stellenbosch University, Tygerberg, South Africa.
J Acquir Immune Defic Syndr. 2011 Apr;56(4):333-9. doi: 10.1097/QAI.0b013e31820dc0cc.
In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.
We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public health antiretroviral clinics in South Africa documenting the prevalence of virologic failure (HIV RNA load >500 copies/mL) and genotypic antiretroviral resistance; and lopinavir hair and plasma concentrations in a nested case-control study.
Ninety-three patients treated with a second-line regimen including lopinavir boosted with ritonavir were included, of whom 50 (25 cases, with virologic failure and 25 controls) were included in a nested case control study. Of 93 patients, 37 (40%) had virological failure, only 2 of them had had major PI mutations. The negative predictive values: probability of failure with lopinavir plasma concentration >1 µg/mL or hair concentrations >3.63 ng/mg for virologic failure were 86% and 89%, and positive predictive values of low concentrations 73% and 79%, respectively, whereas all virologic failures with HIV RNA loads above 1000 copies per milliliter, of patients without PI resistance, could be explained by either having a low lopinavir concentration in plasma or hair.
Most patients who fail a lopinavir/ritonavir regimen, in our setting, have poor lopinavir exposure. A threshold plasma lopinavir concentration (indicating recent lopinavir/ritonavir use) and/or hair concentration (indicating longer term lopinavir exposure) are valuable in determining the aetiology of virologic failure and identifying patients in need of adherence counselling or resistance testing.
在资源有限的环境下，许多患者在二线治疗中没有使用过蛋白酶抑制剂（PI），采用高基因屏障、含利托那韦增强剂的 PI 方案治疗，结果病毒学治疗失败。
我们进行了一项横断面调查，以研究南非 2 家公共卫生抗逆转录病毒诊所中病毒学治疗失败的病因，记录病毒学治疗失败（HIV RNA 载量>500 拷贝/mL）和基因型抗逆转录病毒耐药的发生率；并在嵌套病例对照研究中检测洛匹那韦的发和血浆浓度。
纳入了 93 例接受二线方案治疗的患者，其中包括利托那韦增强的洛匹那韦，其中 50 例（25 例病例，病毒学治疗失败，25 例对照）纳入了嵌套病例对照研究。93 例患者中，37 例（40%）出现病毒学治疗失败，只有 2 例有主要 PI 突变。洛匹那韦血浆浓度>1μg/mL 或发浓度>3.63ng/mg 时，对病毒学治疗失败的阴性预测值分别为 86%和 89%，而低浓度时的阳性预测值分别为 73%和 79%，然而，所有 HIV RNA 载量>1000 拷贝/mL 的病毒学治疗失败患者，如果没有 PI 耐药，都可以通过血浆或发中洛匹那韦浓度较低来解释。
在我们的环境中，大多数洛匹那韦/利托那韦方案治疗失败的患者洛匹那韦暴露情况较差。血浆洛匹那韦浓度（表明近期使用洛匹那韦/利托那韦）和/或发浓度（表明长期洛匹那韦暴露）的阈值对确定病毒学治疗失败的病因以及识别需要接受依从性咨询或耐药性检测的患者非常有价值。
