Mikasi Sello Given, Gichana Josiah Otwoma, Van der Walt Cheri, Brado Dominik, Obasa Adetayo Emmanuel, Njenda Duncan, Messembe Martha, Lyonga Emilia, Assoumou Okomo, Cloete Ruben, Ikomey George Mondinde, Jacobs Graeme Brendon
Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Division of Oral Surgery, Department of Pathology Laboratory, University of Nairobi, Nairobi, Kenya.
AIDS Res Hum Retroviruses. 2020 May;36(5):450-455. doi: 10.1089/AID.2019.0264. Epub 2020 Jan 13.
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 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.% ( = 20/37) and 45.9% ( = 17/37), other subtype viral sequences include (A, CRF36_cpx, F,G, and C). A total of 18.9% ( = 7/37) of the sequences had RAMs, with only 5.4% ( = 2/37) having major RAMs (Y143R/C/D/G and P145S), against INSTIs. Accessory RAMs were present in 8.1% ( = 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.
世界卫生组织(WHO)已提出建议,将整合酶(IN)链转移抑制剂(INSTIs)作为治疗HIV感染的一线联合抗逆转录病毒治疗方案的一部分。在资源有限的环境(RLS)中,关于INSTIs的治疗前耐药性的知识仍然匮乏。我们对喀麦隆56例初治患者的病毒序列中的基因进行了特征分析,以识别耐药相关突变(RAMs)。研究分析使用了37条片段大小≥500 bp或质量良好的序列。大多数序列被鉴定为CRF02_AG,占54%(n = 20/37),其他亚型病毒序列占45.9%(n = 17/37),包括(A、CRF36_cpx、F、G和C)。共有18.9%(n = 7/37)的序列存在RAMs,其中只有5.4%(n = 2/37)具有主要RAMs(Y143R/C/D/G和P145S),对抗INSTIs。8.1%(n = 3/37)的序列存在辅助RAMs,其中一个序列仅包含E157Q,另一个包含Q95K。一个患者序列有三个辅助RAMs(G140E、E157Q和G163R)。我们鉴定出了对INSTIs的主要RAMs,这可能会对包括喀麦隆在内的资源有限环境中多替拉韦的推广产生潜在临床影响。这是第一项描述喀麦隆感染CRF02_AG和其他亚型的初治HIV-1感染者(PLHIV-1)中RAMs的研究。