McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
J Antimicrob Chemother. 2011 Oct;66(10):2346-9. doi: 10.1093/jac/dkr291. Epub 2011 Jul 12.
M184V in HIV-1 reverse transcriptase is among the most common mutations in patients failing antiretroviral therapy but is found only rarely in cases of transmitted drug resistance.
To investigate this apparent paradox, we developed an allele-specific real-time PCR (AS-PCR) assay to determine the transmission of M184V in newly infected individuals.
M184V transmission may occur to a greater extent than previously thought. Persistence of M184V may commonly involve linkage to other drug resistance mutations. The presence of M184V as a single substitution in newly infected individuals was shown to wane over time, as a likely consequence of reversion and overgrowth by more fit wild-type viruses.
The M184V mutation can be documented in newly infected individuals, and the alternative hypothesis that this substitution might impact on the ability of HIV to be transmitted is unfounded.
HIV-1 逆转录酶中的 M184V 突变是抗逆转录病毒治疗失败患者中最常见的突变之一,但在传播耐药性病例中却很少发现。
为了解决这一明显的悖论,我们开发了一种等位基因特异性实时 PCR(AS-PCR)检测方法,以确定新感染个体中 M184V 的传播情况。
M184V 的传播可能比以前认为的更为普遍。M184V 的持续存在通常涉及与其他耐药性突变的连锁。在新感染的个体中,M184V 作为单一替代物的存在随着时间的推移而减弱,这可能是由于更适合野生型病毒的回复和过度生长所致。
可以在新感染的个体中检测到 M184V 突变,而替代假设即这种替代可能影响 HIV 的传播能力是没有根据的。