Nevirapine Resistance in Women who Received Nevirapine for PMTCT HIV

描述（由申请方提供）：南部非洲HIV-1流行的特点是C亚型感染占优势。这是博茨瓦纳的主要亚型，估计成年人的艾滋病毒流行率为37%。世界卫生组织关于到2005年向300万人提供抗逆转录病毒药物的目标，将为大量艾滋病毒感染者提供机会，使他们变得健康，过上有意义的生活。 然而，抗逆转录病毒药物的引入需要伴随着对非亚型B分支中病毒耐药性的进一步研究，因为对这些亚型的耐药性的了解有限。要检查的中心假设是，更灵敏的检测方法可以检测到接受奈韦拉平预防母婴传播（PMTCT）的妇女的病毒耐药性，并且一旦妇女开始抗逆转录病毒药物治疗，该信息可以预测临床结果。为了解决这一假设，我们正在优化寡核苷酸连接试验和等位基因特异性真实的时间聚合酶链反应技术的样品，已知含有耐药突变。这些HIV-1 C特异性检测试剂盒将用于临床样本，以检测两个最常见的耐奈韦拉平位点的突变。将探索微小变异耐药的临床相关性，因为这些技术将应用于接受PMTCT后常规基因分型技术未检测到耐药突变的女性样本。如果通过这些更敏感的方法检测到导致临床病毒学失败的微小变异，则这些变异可能在解释接受非核苷类逆转录酶抑制剂治疗的患者的病毒学失败方面具有重要作用。所进行的分析还将解决一些问题，如随时间推移突变的持续性和单次给药奈韦拉平后不同病毒储库的耐药模式的变化。这项研究的公共卫生意义是重要的，因为它将提供一个更完整的了解耐药性后单剂量奈韦拉平，并将其与临床结果的妇女谁接受这种治疗，然后开始抗逆转录病毒药物。对单次给药后奈韦拉平耐药性及其对未来孕产妇健康的影响的研究有助于增加对非B亚型艾滋病毒耐药性问题的认识，有助于有关防止母婴传播的公共政策决策，并有助于在资源匮乏的环境中迅速扩大抗逆转录病毒药物使用期间改善对患者的护理。

DESCRIPTION (provided by applicant): The epidemic of HIV-1 in southern Africa is characterized by the predominance of infections caused by subtype C. This is the major subtype in Botswana where HIV prevalence in adults is estimated to be 37%. The goals of the World Health Organization to provide antiretrovirals (ARVs) to three million people by 2005 will provide an opportunity for great numbers of people to become healthy and live productive lives with HIV. This introduction of ARVs, however, needs to be accompanied by further research into viral resistance in the non-subtype B clades as limited knowledge exists about resistance in these subtypes. The central hypothesis to be examined is that more sensitive assays can detect viral resistance in women who have received nevirapine for the prevention of mother-to-child transmission (PMTCT) and that this information can predict clinical outcomes once the women commence ARVs. To address this hypothesis, we are optimizing both an oligonucleotide ligation assay and allele specific real time-polymerase chain reaction technique on samples which are known to contain resistant mutations. These assays, specific to HIV-1 C, will be used on clinical samples to detect mutations at the two most common sites which confer nevirapine resistance. The clinical relevance of minor variant resistance will be explored as these techniques will be applied to samples from women in whom conventional genotyping techniques have not detected resistance mutations after receiving PMTCT. If minor variants causing clinical virologic failure are detected by these more sensitive methods, these variants may have an important role in explaining virologic failure in patients receiving nonnucleoside reverse transcriptase inhibitor therapy. The analyses conducted will also address issues such as the persistence of mutations over time and variations in resistance patterns across different viral reservoirs after single-dose nevirapine. The public health implications of this research are significant in that it will provide a more complete understanding of resistance after single-dose nevirapine and correlate it with clinical outcomes for the women who receive this therapy and then start on ARVs. Research into nevirapine resistance after single-dose and its impact on future maternal health can help to increase the fund of knowledge about issues of resistance in non-subtype B HIV, help with public policy decisions about PMTCT, and serve to improve the care of patients during the rapid expansion of ARV use in resource-poor settings.