United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
J Int AIDS Soc. 2018 Nov;21(11):e25204. doi: 10.1002/jia2.25204.
Thailand plays a substantial role in global HIV-1 transmission of CRF01_AE. Worldwide, men who have sex with men (MSM) are at elevated risk for HIV-1 infection. Hence, understanding HIV-1 diversity in a primarily Thai MSM cohort with acute infection, and its connections to the broader HIV-1 transmission network in Asia is crucial for research and development of HIV-1 vaccines, treatment and cure.
Subtypes and diversity of infecting viruses from individuals sampled from 2009 to 2015 within the RV254/SEARCH 010 cohort were assessed by multiregion hybridization assay (MHAbce), multiregion subtype-specific PCR assay (MSSPbce) and full-length single-genome sequencing (SGS). Phylogenetic analysis was performed by maximum likelihood. Pairwise genetic distances of envelope gp160 sequences obtained from the cohort and from Asia (Los Alamos National Laboratory HIV Database) were calculated to identify potential transmission networks.
MHAbce/MSSPbce results identified 81.6% CRF01_AE infecting strains in RV254. CRF01_AE/B recombinants and subtype B were found at 7.3% and 2.8% respectively. Western subtype B strains outnumbered Thai B' strains. Phylogenetic analysis revealed one C, one CRF01_AE/CRF02_AG recombinant and one CRF01_AE/B/C recombinant. Asian network analysis identified one hundred and twenty-three clusters, including five clusters of RV254 participants. None of the RV254 sequences clustered with non-RV254 sequences. The largest international cluster involved 15 CRF01_AE strains from China and Vietnam. The remaining clusters were mostly intracountry connections, of which 31.7% included Thai nodes and 43.1% included Chinese nodes.
While the majority of strains in Thailand are CRF01_AE and subtype B, emergence of unique recombinant forms (URFs) are found in a moderate fraction of new HIV-1 infections. Approaches to vaccine design and immunotherapeutics will need to monitor and consider the expanding proportion of recombinants and the increasing genetic diversity in the region. Identified HIV-1 transmission networks indicate ongoing spread of HIV-1 among MSM. As HIV-1 epidemics continue to expand in other Asian countries, transmission network analyses can inform strategies for prevention, intervention, treatment and cure.
泰国在全球 HIV-1 CRF01_AE 传播中发挥了重要作用。在全球范围内，男男性行为者（MSM）感染 HIV-1 的风险较高。因此，了解主要为泰国 MSM 群体中急性感染的 HIV-1 多样性及其与亚洲更广泛的 HIV-1 传播网络的关系，对于 HIV-1 疫苗、治疗和治愈的研究和开发至关重要。
通过多区域杂交测定法（MHAbce）、多区域亚型特异性聚合酶链反应测定法（MSSPbce）和全长单基因序列测定法（SGS）评估 2009 年至 2015 年在 RV254/SEARCH 010 队列中采样的个体感染病毒的亚型和多样性。通过最大似然法进行系统发育分析。计算从队列和亚洲（洛斯阿拉莫斯国家实验室 HIV 数据库）获得的包膜 gp160 序列的成对遗传距离，以识别潜在的传播网络。
MHAbce/MSSPbce 结果确定 RV254 中有 81.6%的 CRF01_AE 感染株。发现 7.3%的 CRF01_AE/B 重组和 2.8%的亚型 B。西方亚型 B 株数超过泰国 B'株数。系统发育分析显示有一个 C、一个 CRF01_AE/CRF02_AG 重组和一个 CRF01_AE/B/C 重组。亚洲网络分析确定了 123 个簇，其中包括 RV254 参与者的 5 个簇。RV254 序列与非 RV254 序列均未聚类。最大的国际簇包括来自中国和越南的 15 株 CRF01_AE 株。其余簇主要是国内连接，其中 31.7%包括泰国节点，43.1%包括中国节点。
尽管泰国的大多数毒株为 CRF01_AE 和亚型 B，但新感染的 HIV-1 中发现了独特重组形式（URFs）的出现。疫苗设计和免疫治疗方法将需要监测和考虑该地区不断扩大的重组比例和不断增加的遗传多样性。确定的 HIV-1 传播网络表明 MSM 中 HIV-1 的持续传播。随着其他亚洲国家的 HIV-1 流行继续扩大，传播网络分析可以为预防、干预、治疗和治愈提供信息。
