Relationship between minority nonnucleoside reverse transcriptase inhibitor resistance mutations, adherence, and the risk of virologic failure.
Relationship between minority nonnucleoside reverse transcriptase inhibitor resistance mutations, adherence, and the risk of virologic failure.
复制标题
DOI：
10.1097/qad.0b013e32834e9d7d
复制
发表时间：
2012-01-14
期刊：
影响因子：
--
通讯作者：
Kuritzkes DR
中科院分区：
文献类型：
--
作者：
Li JZ;Paredes R;Ribaudo HJ;Svarovskaia ES;Kozal MJ;Hullsiek KH;Miller MD;Bangsberg DR;Kuritzkes DR
评价非核苷类逆转录酶抑制剂（NNRTI）依从性欠佳和少数NNRTI耐药突变导致病毒学失败的风险。汇总分析了来自三项研究的少数NNRTI耐药突变和NNRTI依从性导致的病毒学失败风险，这些研究针对的是启动基于NNRTI方案的初治个体。每项研究的参与者分为依从性四分位数（Q1-Q4）和四个分层：≥ 95%，80- 94%，60- 79%和<60%。加权考克斯比例风险模型用于估计病毒学失败的风险。大多数参与者（N=768）具有较高的测量依从性，但依从性最低的四分位数中病毒学失败的参与者比例最高，并且病毒学失败的风险随着依从性低于95%而逐步增加。少数NNRTI耐药突变的检测增加了依从性四分位数中病毒学失败的参与者比例（Cochran-Mantel-Haenszel P<0.001）和依从性分层（Cochran-Mantel-Haenszel P<0.001; <60%依从性，HR 1.7 [1.1-2.7]，P=0.02; 60-79%依从性，HR 1.2 [0.5-3.2]，P=0.67; 80-94%依从性，HR 2.5 [0.98-6.3]，P=0.06; ≥95%依从性，HR 3.6 [2.3-5.6]，P<0.001）。在多变量分析中，少数变量的影响在较高水平的药物依从性中也最为突出。少数NNRTI耐药突变和NNRTI依从性的存在被认为是病毒学失败的独立预测因子，但也改变了彼此对病毒学失败的影响。除了关注药物依从性咨询外，超灵敏的HIV-1耐药性检测可以在优化一线抗逆转录病毒治疗的成功率方面发挥作用。
To evaluate the risk of virologic failure conferred by suboptimal adherence to non-nucleoside reverse transcriptase inhibitors (NNRTI) and minority NNRTI resistance mutations. Pooled analysis of the risk of virologic failure conferred by minority NNRTI resistance mutations and NNRTI adherence from three studies of treatment-naïve individuals initiating an NNRTI-based regimen. Participants from each study were categorized into both adherence quartiles (Q1–Q4) and four strata: ≥95%, 80–94%, 60–79%, and <60%. Weighted Cox proportional hazard models were used to estimate the risk of virologic failure. The majority of participants (N=768) had high measured adherence, but those in the lowest adherence quartile had the highest proportion of participants with virologic failure and the risk of virologic failure increased step-wise with adherence below 95%. Detection of minority NNRTI drug resistance mutations increased the proportion of participants with virologic failure across adherence quartiles (Cochran-Mantel-Haenszel P<0.001) and adherence strata (Cochran-Mantel-Haenszel P<0.001; <60% adherence, HR 1.7 [1.1–2.7], P=0.02; 60–79% adherence, HR 1.2 [0.5–3.2], P=0.67; 80–94% adherence, HR 2.5 [0.98–6.3], P=0.06; ≥95% adherence, HR 3.6 [2.3–5.6], P<0.001). On multivariate analysis, the effect of minority variants was also most prominent at higher levels of medication adherence. The presence of minority NNRTI resistance mutations and NNRTI adherence were found to be independent predictors of virologic failure, but also modify each other’s effects on virologic failure. In addition to the focus on medication adherence counseling, ultrasensitive HIV-1 drug resistance assays could play a role in optimizing the success rates of first-line antiretroviral therapy.