Table_4_The Molecular Epidemiological and Immunological Characteristics of HIV-1 CRF01_AE/B Recombinants in Nanjing, China.DOCX

Human immunodeficiency virus-type 1 (HIV-1) CRF01_AE/B recombinants are newly emerging strains that are spreading rapidly in Southern and Eastern China. This study aimed to elucidate the molecular epidemiological characteristics of HIV-1 CRF01_AE/B recombinants in Nanjing and to explore the impact of these novel strains on the immunological status. A total of 1,013 blood samples from newly diagnosed HIV-1-infected patients were collected in Nanjing from 2015 to 2019, among which 958 partial Pol sequences were sequenced successfully. We depicted the molecular epidemiological characteristics of CRF01_AE/B recombinants by the molecular evolutionary analysis, Bayesian system evolution analysis, and transmission network analysis. The generalized additive mixed model was applied to evaluate the CD4+ T-cell count change of CRF01_AE/B recombinants. The Kaplan–Meier analysis was performed to assess the time from combined antiretroviral therapy (cART) initiation to immune reconstruction. We have identified 102 CRF01_AE/B recombinants (102/958, 10.65%) in Nanjing, including CRF67_01B (45/102, 44.12%), CRF68_01B (35/102, 34.31%), and CRF55_01B (22/102, 12.57%). According to the Bayesian phylogenetic inference, CRF55_01B had a rapid decline stage during 2017–2019, while CRF67_01B and CRF68_01B have experienced a fast growth phase during 2014–2015 and then remained stable. We have constructed 83 transmission networks, in which three larger clusters were composed of CRF67_01B and CRF68_01B. CRF01_AE/B recombinants manifested a faster decrease rate of CD4+ T-cell count than CRF_07BC but similar to CRF01_AE. The probability of achieving immune reconstruction in CRF01_AE/B recombinants was lower than CRF07_BC in the subgroup of baseline CD4+ T-cell count at cART initiation

人类免疫缺陷病毒1型（HIV-1）CRF01_AE/B重组株为新兴的病毒株，在中国南方和东部地区迅速传播。本研究旨在阐明南京地区HIV-1 CRF01_AE/B重组株的分子流行病学特征，并探究这些新型株对免疫状态的潜在影响。2015年至2019年间，在南京收集了1,013份新诊断的HIV-1感染者的血液样本，其中958份部分Pol序列成功测序。通过分子进化分析、贝叶斯系统进化分析和传播网络分析，描绘了CRF01_AE/B重组株的分子流行病学特征。应用广义加性混合模型评估了CRF01_AE/B重组株的CD4+ T细胞计数变化。进行Kaplan-Meier分析以评估从联合抗逆转录病毒治疗（cART）开始到免疫重建的时间。在南京共鉴定出102株CRF01_AE/B重组株（占958株中的102株，比例为10.65%），包括CRF67_01B（占102株中的45株，比例为44.12%）、CRF68_01B（占102株中的35株，比例为34.31%）和CRF55_01B（占102株中的22株，比例为12.57%）。根据贝叶斯系统发育推断，CRF55_01B在2017-2019年间经历了快速下降阶段，而CRF67_01B和CRF68_01B在2014-2015年间经历了快速增长阶段，之后保持稳定。构建了83个传播网络，其中三个较大的簇由CRF67_01B和CRF68_01B组成。与CRF_07BC相比，CRF01_AE/B重组株表现出更快的CD4+ T细胞计数下降率，与CRF01_AE相似。在cART起始时基线CD4+ T细胞计数较低的亚组中，CRF01_AE/B重组株实现免疫重建的概率低于CRF07_BC。