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HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon.
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-04-30 , DOI: 10.1089/aid.2019.0264
Sello Given Mikasi 1 , Josiah Otwoma Gichana 2 , Cheri Van der Walt 1 , Dominik Brado 3 , Adetayo Emmanuel Obasa 1 , Duncan Njenda 1, 4 , Martha Messembe 5 , Emilia Lyonga 5 , Okomo Assoumou 5 , Ruben Cloete 6 , George Mondinde Ikomey 5 , Graeme Brendon Jacobs 1
Affiliation  

The World Health Organization (WHO) has put forth recommendations for the use of integrase (IN) strand transfer inhibitors (INSTIs) to be part of the first-line combination antiretroviral therapy regimen to treat HIV infections. The knowledge of pretreatment drug resistance against INSTIs is still scarce in resource-limited settings (RLS). We characterized the integrase gene to identify resistance-associated mutations (RAMs) in 56 INSTI-naive patient viral sequences from Cameroon. Study analysis used 37 sequences with fragment size ≥500 bp or of good quality .The majority of the sequences were identified as CRF02_AG 54.% (n = 20/37) and 45.9% (n = 17/37), other subtype viral sequences include (A, CRF36_cpx, F,G, and C). A total of 18.9% (n = 7/37) of the sequences had RAMs, with only 5.4% (n = 2/37) having major RAMs (Y143R/C/D/G and P145S), against INSTIs. Accessory RAMs were present in 8.1% (n = 3/37) of the sequences, of which one sequence contained solely E157Q, and another Q95K. One patient sequence had three accessory RAMs (G140E, E157Q, and G163R). We identified major RAMs to INSTIs, which might have a potential clinical impact to dolutegravir rollout in RLS, including Cameroon. This is the first study to describe RAMs among INSTI-naive people living with HIV-1 (PLHIV-1) infected with CRF02_AG and other subtypes in Cameroon.

中文翻译:

来自喀麦隆的整合酶原转移抑制因子幼稚的HIV-1患者中的HIV-1整合酶多样性以及与耐药相关的突变和多态性。

世界卫生组织(WHO)提出了使用整合酶(IN)链转移抑制剂(INSTI)的建议,以作为治疗HIV感染的一线联合抗逆转录病毒疗法的一部分。在资源有限的环境(RLS)中,对INSTIs的预处理药物耐药性的知识仍然很少。我们表征了整合酶基因,以鉴定来自喀麦隆的56位INSTI天真患者病毒序列中的耐药相关突变(RAM)。研究分析使用了片段大小≥500 bp或质量良好的37个序列,其中大多数 亚型病毒序列被鉴定为CRF02_AG 54.%(n  = 20/37)和45.9%(n = 17/37)包括(A,CRF36_cpx,F,G和C)。总计18.9%(n = 7/37)的序列具有RAM,只有5.4%(n  = 2/37)具有针对INSTI的主要RAM(Y143R / C / D / G和P145S)。附件RAM占 序列的8.1%(n = 3/37),其中一个序列仅包含E157Q,另一个包含Q95K。一个患者序列具有三个辅助RAM(G140E,E157Q和G163R)。我们确定了INSTIs的主要RAM,这可能会对在包括喀麦隆在内的RLS中推出dolutegravir产生潜在的临床影响。这是第一项描述喀麦隆INSTI天真感染HIV-1(PLHIV-1)感染CRF02_AG和其他亚型的人中RAM的研究。
更新日期:2020-04-30
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