Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, China.
J Clin Virol. 2013 Sep;58(1):233-9. doi: 10.1016/j.jcv.2013.05.022. Epub 2013 Jun 25.
Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT.
To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother-infant pairs to maraviroc.
Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were employed to construct provirus clones and to analyze the sensitivity to maraviroc.
Mutations A316T, conferring partial resistance to maraviroc, T307I and R315Q, both conferring partial resistance to vicriviroc are prevalent in mother and infant cohorts, indicating the transmission of primary resistance mutations during HIV-1 perinatal transmission. However, the mutations of acutely infected mothers seem to directly transmit to their corresponding infants, while some mutations at low frequency of chronically infected mothers would be lost during transmission. Moreover, provirus clones derived from acutely infected MIPs are less susceptible to maraviroc than those from chronically infected MIPs.
Our study suggests that the transmission mode of primary resistance mutations and the sensitivity to maraviroc are dependent on infection status of MIPs either acutely or chronically infected. These results may indicate that higher dose of maraviroc could be needed for treatment of acutely infected MIPs compared to chronically infected MIPs.
小分子 CCR5 抑制剂是治疗 HIV-1 感染的一类新药。在 HIV-1 围产期传播过程中，需要评估与进入抑制剂相关的原发性耐药突变，因为它们可能对母婴传播的临床管理产生深远影响。
评估围产期传播过程中马拉维若和维立西罗对 maraviroc 的原发性耐药突变，并分析来自母婴对 maraviroc 的敏感性。
招募了 9 例感染 C 型 HIV-1 的 MIPs，分析了马拉维若和维立西罗原发性耐药突变的流行情况和传播情况。此外，来自 6 例 MIPs 的 Env 被用于构建前病毒克隆，并分析其对 maraviroc 的敏感性。
A316T 突变赋予对马拉维若的部分耐药性，T307I 和 R315Q 突变赋予对 vicriviroc 的部分耐药性，在母婴队列中均很常见，表明 HIV-1 围产期传播过程中存在原发性耐药突变的传播。然而，急性感染母亲的突变似乎直接传递给其相应的婴儿，而慢性感染母亲的一些低频突变在传递过程中会丢失。此外，来自急性感染 MIPs 的前病毒克隆对 maraviroc 的敏感性低于来自慢性感染 MIPs 的前病毒克隆。
我们的研究表明，原发性耐药突变的传播模式和对 maraviroc 的敏感性取决于 MIPs 的感染状态，无论是急性感染还是慢性感染。这些结果可能表明，与慢性感染 MIPs 相比，急性感染 MIPs 需要更高剂量的 maraviroc 进行治疗。
