在抗逆转录病毒治疗的管理中,应该如何考虑APOBEC3诱导的耐药性突变?
Marie Gilbert1, Valentine Marie Ferré2,3, Romane Guilbaud2
1Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Bichat-Claude Bernard, F-75018 Paris, France.
The Journal of antimicrobial chemotherapy
|September 28, 2025
概括
在HIV-DNA基因型耐药性测试中,APOBEC3诱导的突变 (APOMuts) 并没有影响潜在的APOMut影响治疗 (PAIT) 艾滋病病毒感染者 (PLWH) 的病毒学结果. 病毒学失败与坚持有关,而不是APOMuts,这表明它们不应该指导ART管理.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 使用细胞相关的HIV-DNA基因型耐药性测试 (GRTs) 进行联合抗逆转录病毒疗法 (ART) 管理是具有挑战性的,原因是APOBEC3诱导的突变 (APOMuts).
- 当APOMuts发生在与药物耐药性相关的位置时,对GRTs的解释可能很困难.
研究的目的:
- 为了评估艾滋病毒感染者 (PLWH) 与携带APOMuts的HIV-DNA前病毒的病毒学结果.
- 评估APOMut对理论上受这些突变影响的ART疗法的影响 (潜在的APOMut影响治疗,PAIT).
主要方法:
- 包括PAIT上的PLWH与含有APOMuts的细胞关联HIV-DNAGRTs (2010年4月至2023年12月).
- 治疗失败的定义是两个连续的血病毒载量值>50副本/毫升至少隔一个月后PAIT切换.
主要成果:
- 在42个PAIT线上研究了38个PLWH;大多数在PAIT引入时被病毒抑制.
- 病毒学失败发生在四个PLWH中,所有这些都与ART的不良坚持或中断有关.
- 一例病毒学失败发生了整合酶抵抗突变 (N155H),并通过含有蛋白酶抑制剂 (PI) 的ART实现了抑制.
结论:
- 在PLWH转换为PAIT时,尽管在HIV-DNAGRTs中存在APOMuts,但病毒抑制仍然存在.
- 病毒学失败与APOMuts的存在没有关联.
- 在治疗PLWH的ART时,不应考虑APOMuts.
相关概念视频
Retrovirus Life Cycles
49.3K
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...
49.3K
Viral Mutations
39.6K
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...
39.6K
Retroviruses
14.6K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
14.6K
Mechanisms of Retrovirus-induced Cancers
6.9K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.9K
Treatment Resistant Cancers
3.7K
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...
3.7K


