Kolomeets Anna N, Varghese Vici, Lemey Philippe, Bobkova Marina R, Shafer Robert W
aOmsk Research Institute of Natural Focal Infections; Siberian Federal District Center For AIDS Prevention and Fight; Omsk, Russia bDivision of Infectious Diseases, Stanford University, Stanford, California, USA cDepartment of Microbiology and Immunology, REGA Institute KU Leuven, University of Leuven, Leuven, Belgium dIvanovsky Research Institute of Virology, Russian Ministry of Health, Moscow, Russia.
AIDS. 2014 Nov 13;28(17):F1-8. doi: 10.1097/QAD.0000000000000485.
The subtype A variant in the Former Soviet Union (A(FSU)) causes most of Russia's HIV-1 infections. However, the spectrum of drug-resistance mutations (DRMs) in antiretroviral experienced patients with this variant has not been studied.
Between 2010 and 2013, genotypic resistance testing was performed on plasma samples from 366 antiretroviral-experienced patients in Siberia.
Three-hundred patients (82%) had subtype A(FSU) and 55 (15%) had CRF02_AG viruses. The pattern of DRMs was consistent with patient antiretroviral history with one exception. G190S was the most common nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation, occurring in 55 (33%) subtype A(FSU) viruses from 167 NNRTI-experienced patients compared with none of 37 CRF02_AG viruses from NNRTI-experienced patients (P < 0.001). The next most common subtype A(FSU) NNRTI-resistance mutation, K103N, occurred in 25 (15%) viruses. Wild-type glycine (G) at position 190 is encoded by GGC in more than 99% of published A(FSU) strains. By contrast, G190 is encoded by GGA or GGG in 97% of other subtypes and in subtype A strains outside of the FSU. Therefore, G190S results from a single G→A transition: G (GGC) → S (AGC) almost exclusively in subtype A(FSU) viruses.
The predisposition of subtype A(FSU) to G190S is concerning because G→A is the most common HIV-1 mutation and because G190S causes higher levels of nevirapine and efavirenz resistance than K103N. This study exemplifies the need for characterizing the genetic mechanisms of resistance in diverse populations and warrants studies to verify that NRTI/NNRTI regimens are as efficacious in treating subtype A(FSU) as viruses belonging to other subtypes.
前苏联的A亚型变异株（A(FSU)）导致了俄罗斯大部分的HIV-1感染。然而，对于有抗逆转录病毒治疗经历的携带该变异株患者的耐药突变（DRMs）谱尚未进行研究。
在2010年至2013年期间，对来自西伯利亚的366例有抗逆转录病毒治疗经历患者的血浆样本进行了基因型耐药检测。
300例患者（82%）感染的是A(FSU)亚型，55例（15%）感染的是CRF02_AG病毒。DRMs模式与患者的抗逆转录病毒治疗史一致，但有一个例外。G190S是最常见的非核苷类逆转录酶抑制剂（NNRTI）耐药突变，在167例有NNRTI治疗经历患者的55株（33%）A(FSU)亚型病毒中出现，而在37例有NNRTI治疗经历患者的CRF02_AG病毒中均未出现（P<0.001）。第二常见的A(FSU)亚型NNRTI耐药突变K103N出现在25株（15%）病毒中。在超过99%已发表的A(FSU)毒株中，190位的野生型甘氨酸（G）由GGC编码。相比之下，在97%的其他亚型以及FSU以外的A亚型毒株中，G190由GGA或GGG编码。因此，G190S几乎仅在A(FSU)亚型病毒中由单个G→A转变导致：G（GGC）→S（AGC）。
A(FSU)亚型易发生G190S令人担忧，因为G→A是最常见的HIV-1突变，且G190S导致的奈韦拉平和依非韦伦耐药水平高于K103N。本研究例证了有必要在不同人群中阐明耐药的遗传机制，并且有必要开展研究以验证核苷类逆转录酶抑制剂/非核苷类逆转录酶抑制剂治疗方案在治疗A(FSU)亚型病毒时与治疗其他亚型病毒一样有效。
