In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen

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• 作者：Jaqueline Souza Cavalcanti^a ; André ; Minhoto Lanç ; a^a ; Joã ; o Leandro de Paula Ferreira^a ; Margareth da Eira^b ; Daniel Soares de Souza Dantas^b ; Luí ; s Fernando de Macedo Brí ; gido^a ; ^{lubrigido@gmail.com}
• 关键词：HIV-1 ; Brazil ; Integrase ; Raltegravir ; Genetic resistance
• 刊名：Antiviral Research
• 出版年：2012
• 期刊代码：7_01663542
• 类别：imm
• 出版时间：July, 2012
• 卷：95
• 期：1
• 页码：9-11
• 文件大小：162 K

摘要

Raltegravir is an integrase inhibitor (INI) licensed for clinical use and other INI are in advanced stage of development. Different resistance mutations in HIV integrase from patients using these antiretroviral drugs have been described and G148H/R/K, N155H and less frequently Y143C/H/R are considered major resistant mutations to raltegravir. Both Stanford Database and Geno2Pheno list F121Y as conferring intermediate resistance 鈥渋n vitro鈥?both to raltegravir and elvitegravir. We report for the first time the 鈥?em>in vivo鈥?selection F121Y and evolution to Y143R in a 31 years old male clade B HIV-1 infected patient failing a raltegravir-containing salvage regimen. Plasma samples nine months prior to raltegravir (RAL-Na茂ve) and at weeks 32, 40 and 88 after RAL-containing regimen were analyzed. Antiretroviral susceptibility was evaluated at Stanford and Geno2Pheno from sequences obtained with RT-PCR. After a Viral load at week 12 below 50 copies/mL, viremia raised at week 20 to 4.5log10. The emergence of F121Y was observed at week 32 and 40, alongside with L74I, T97A, Q137H and V151I. At week 88 F121Y was no longer detected, L74I and T97A were maintained and Y143R emerged. F121Y might be an alternative pathway to Y143R. Changing of RAL-containing regimen upon the identification of F121Y might avoid the evolution of raltegravir resistance.