相关实验视频
Updated: May 31, 2025
05:46
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
17.8K
评估基于整合酶链转移抑制剂 (INSTI) 的耐药替代物的表型效应,与卡博特格拉维尔失败相关
Michelle L D'Antoni1, Brie Falkard1, Kristen Andreatta1
1Clinical Virology, Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.
The Journal of antimicrobial chemotherapy
|January 24, 2025
概括
整合酶链转移抑制剂 (INSTI) 耐药性突变,特别是卡博特格拉维尔所见的突变,显著降低了比克特格拉维尔和埃尔维特格拉维尔的有效性. 这凸显了未来艾滋病毒治疗选择面临的潜在挑战.
科学领域:
- 病毒学 病毒学
- 传染性疾病 传染性疾病
- 药理学 药理学是指药理学的学科.
背景情况:
- 推基于整合酶链转移抑制剂 (INSTI) 的疗法用于艾滋病毒治疗.
- INSTI耐药性的出现可能会影响后续的治疗选择.
- 在病毒学失败和血清转化中记录了卡博特格拉维尔耐药性模式.
研究的目的:
- 评估比克特格拉维尔和埃尔维特格拉维尔对具有卡博特格拉维尔相关耐药突变的临床隔离物的抗病毒活性.
- 了解特定的INSTI耐药性相关突变 (RAMs) 对已批准的INSTI疗效的影响.
主要方法:
- 用于测量对卡博特格拉维尔,比克特格拉维尔和埃尔维特格拉维尔敏感性的表型测定.
- 测试了52种具有模仿卡博特格拉维尔INSTI耐药性的耐药性配置的临床分离物.
- 以单,双或三重RAM为特征的分离物,包括Q148K/R,N155H,R263K,G118R,E138A/K和G140A/S. 这些分离物.
主要成果:
- 三重RAM显示IC50值的最高折叠变化 (FC):卡博特格拉维尔47.0,比克特格拉维尔7.59,埃尔维特格拉维尔>144.
- 在所有测试的INSTIs中,在双重和单重RAM中观察到IC50 FC的显著增加.
- 54%的分离物仍然对比克特格拉维尔敏感,而100%对埃尔维特格拉维尔耐药.
结论:
- 与卡博特格拉维尔相关的耐药性模式的临床分离体显示出IC50折叠变化增加.
- 卡博特格拉维尔耐药性可能会损害基于比克特格拉维尔和埃尔维特格拉维尔的HIV治疗方案的疗效.
- 了解耐药性模式对于优化未来的HIV治疗选择至关重要.
相关概念视频
01:10Retrovirus Life Cycles
45.6K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
45.6K
00:36Viral Mutations
32.1K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.1K
02:56Treatment Resistant Cancers
3.2K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K