Abstract：Objective To explore the intra-host genetic evolution of HIV-1 pol gene via follow-up for treatment-naïve HIV infections, and estimate the infection time with Bayesian coalescent theory, so as to support the evaluation of HIV epidemic. Methods Five cases were recruited and followed up. The pol gene fragments were amplified for the characteristics of transmitted drug resistance ( TDR ) by RT-PCR. Bayesian coalescent theory was utilized to construct maximum clade credibility ( MCC ) tree for genetic evolution and calculate the time to the most recent common ancestor ( tMRCA ). Results The five cases were all male, and aged from 27 to 50 years old.Five to nine sampling times were obtained from each case, and the pol gene sequences from each case formed a unique subcluster (posterior probability: 100% ), with different evolution characteristics, in the MCC tree. The three cases in primary HIV-1 infection were estimated to be infected one to five months before the first positive reaction of HIV screening, whereas the two HIV-1 diagnosed cases at first screening were extrapolated to get infected fourteen months and seven months before diagnosis, respectively. One case with acute HIV-1 infection carried TDR mutation ( M46I ) , expressing fast disease progress and quasispecies variation. Conclusions The general infection time can be estimated by analyzing the characteristics of intra-host genetic evolution of HIV-1 pol gene with Bayesian coalescent theory, and this method can help to estimate the HIV epidemic.
辛若雷, 李佳, 孙丽君, 刘安, 张琴, 孙伟东, 李洁, 卢红艳, 白立石. 5例HIV-1感染者pol基因进化和感染时间推断研究[J]. 预防医学, 2021, 33(6): 545-550.
XIN Ruolei, LI Jia, SUN Lijun, LIU An, ZHANG Qin, SUN Weidong, LI Jie, LU Hongyan, BAI Lishi. Intra-host genetic evolution of HIV-1 pol gene and estimation of infection time for five infections. Preventive Medicine, 2021, 33(6): 545-550.
 吕繁,陈方方.艾滋病疫情估计及结果解读要点[J].中华流行病学杂志,2019,40(10):1191-1196.  ZHAO Y,HAN M J,MA Y,et al.Progress towards the 90-90-90 targets for controlling HIV-China,2018[J].China CDC Weekly,2019,1:4-7.  MOYO S,WILKINSON E,VANDORMAEL A,et al.Pairwise diversity and tMRCA as potential markers for HIV infection recency[J].Medicine(Baltimore),2017,96(6):e6041.  CHEN Q,SUN Y,SUN W,et al.Trends of HIV incidence and prevalence among men who have sex with men in Beijing,China:nine consecutive cross-sectional surveys,2008-2016[J].PLoS One,2018,13(8):e0201953.  王译葵,刘平,刘静,等.应用HIV感染的常规检测指标辅助判定新发感染的研究[J].中华实验和临床病毒学杂志,2020,34(6):594-599.  KARATZAS-DELGADO E F,RUIZ-GONZÁLEZ V,GARCÍA- CISNEROS S,et al.Evaluation of an HIV recent infection testing algorithm with serological assays among men who have sex with men in Mexico[J].J Infect Public Health,2020,13(4):509-513.  KONIKOFF J,BROOKMEYER R,LONGOSZ A F,et al.Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States[J].PLoS One,2013,8(12):e82772.  PARK S Y,LOVE T M,PERELSON A S,et al.Molecular clock of HIV-1 envelope genes under early immune selection[J].Retrovirology,2016,13(1):38.  FENG Y,HE X,HSI J H,et al.The rapidly expanding CRF01_AE epidemic in China is driven by multiple lineages of HIV-1 viruses introduced in the 1990s[J].AIDS,2013,27(11):1793-1802.  SU L,FENG Y,LIANG S,et al.The origin and spread of CRF85_BC,driven by heterosexual transmission among older people in Sichuan,China[J].BMC Infect Dis,2020,20(1):772.  HASELKORN T,KUNSTMAN K,BUNCE M,et al.Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960[J].Nature,2008,455(7213):661-664.  孙伟东,姜天俊,黄辉煌,等.北京地区HIV-1感染者治疗前耐药特征及2年抗病毒治疗效果研究[J].国际病毒学杂志,2020,27(3):224-227.  LI Z,HE X,WANG Z,et al.Tracing the origin and history of HIV-1 subtype B'epidemic by near full-length genome analyses[J].AIDS,2012,26(7):877-884.  CURTIS K A,CAMPBELL E M,HANSON D L,et al.A multiplex HIV incidence assay for inferring recent HIV-1 transmission and time of infection[J].J Acquir Immune Defic Syndr,2019,80(4):454-460.  STEKLER J D,TAPIA K,MAENZA J,et al.No time to delay! Fiebig stages and referral in acute HIV infection:Seattle primary infection program experience[J].AIDS Res Hum Retroviruses,2018,34(8):657-666.  辛若雷,孙丽君,李佳,等.单基因组测序分析病毒学失败HIV-1感染者耐药发生特征研究[J].中华微生物学和免疫学杂志,2020,40(12):916-922.  CUI H L,GENG W Q,SUN H,et al.Rapid CD4+T-cell decline is associated with coreceptor switch among MSM primarily infected with HIV-1 CRF01_AE in Northeast China[J].AIDS,2019,33(1):13-22.  NOVITSKY V,WANG R,ROSSENKHAN R,et al.Intra-host evolutionary rates in HIV-1 C env and gag during primary infection[J].Infect Genet Evol,2013,19:361-368.  王丽艳,秦倩倩,葛琳,等.我国50岁及以上艾滋病病毒感染者/艾滋病患者特征分析[J].中华流行病学杂志,2016,37(2):222-226.  LEELAWIWAT W,PATTANASIN S,SRIPORN A,et al.Association between HIV genotype,viral load and disease progression in a cohort of Thai men who have sex with men with estimated dates of HIV infection[J].PLoS One,2018,13(7):e0201386.  GRAY R R,PARKER J,LEMEY P,et al.The mode and tempo of hepatitis C virus evolution within and among hosts[J].BMC Evol Biol,2011,11:131.