Liu Yongjian, Zhang Yu, Li Hanping, Wang Xiaolin, Jia Lei, Han Jingwan, Li Tianyi, Li Jingyun, Li Lin
Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
BMC Infect Dis. 2020 Apr 28;20(1):313. doi: 10.1186/s12879-020-05007-5.
There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance.
We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database.
A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients.
This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.
越来越多的证据表明，HIV-1基因多样性会对耐药性产生影响。本研究旨在调查CRF65_cpx的流行病学情况以及该变异体的自然多态性对基因型耐药性的影响。
我们使用BLAST搜索程序，随后进行系统发育分析，从洛斯阿拉莫斯HIV序列数据库中识别额外的CRF65_cpx pol序列。通过估计最大似然系统发育来阐明CRF65_cpx毒株的流行病学关系。通过将序列提交到斯坦福HIV耐药数据库来确定基因型耐药性。
共获得32条CRF65_cpx pol序列。在地理距离较远的七个省份检测到CRF65_cpx毒株。云南的CRF65_cpx序列主要来自异性传播风险群体，而其他省份的CRF65_cpx序列几乎完全来自男男性行为者群体。除了一个V179E例外，其他31株毒株携带V179D突变。在7名初治男男性行为者患者中检测到V179D和K103R组合，该组合对依非韦伦和奈韦拉平具有中等耐药性。
本研究证实了CRF65_cpx在中国的传播。此外，我们发现HIV-1 CRF65_cpx中自然存在与对非核苷类逆转录酶抑制剂耐药相关的V179D和K103R/V179D突变。我们的研究结果突出了多态性突变对耐药性的影响，并强调了治疗携带CRF65_cpx毒株患者的挑战。
