Molecular Network Technology Was Used To Analyze The Spread Of HIV-1 Strain And The Characteristics Of Drug Resistance

BackgroundSince the national free antiviral treatment program was launched in China in 2003,the incidence of HIV/AIDS-related morbidity and mortality has dropped dramatically.However,the spread of HIV strains and transmitted drug resistance?TDR?mutations still needs attention.HIV strains can be transmitted through social networks.The characteristics of the network determine the speed of disease transmission and can provide evidence for the prevention and treatment of AIDS.In this study,molecular networks were constructed to analyze the characteristics of HIV transmission and drug resistance.Objective1.Describe the spread of TDR among drug-naive individuals and the changes in recent ten years in China.Analyze the transmission characteristics of HIV strains in China by molecular networks.Analyze the TDR and transmission characteristics of newly discovered circulating recombinant forms?CRFs?in China.2.Describe the subtypes and TDR of HIV-positive individuals in Beijing during 2005 to 2015,and construct molecular networks to analyze the transmission and TDR characteristics of HIV strains in Beijing.ResultsThe first sectionThis study investigated 5,627 newly diagnosed HIV-infected individuals in China from April to June 2015.Among 4704 sequenced individuals,the major subtypes were CRF01_AE?39.0%?and CRF07 BC?35.6%?.The total rate of TDR was 3.6%.The prevalence of TDR to nonnucleoside reverse transcriptase inhibitors?NNRTIs?was 1.6%,followed by TDR to nucleoside reverse transcriptase inhibitors?NRTIs?at 1.3%,protease inhibitors?PIs?at 1.1%and multi-drug resistance at 0.5%.The drug resistance mutations?DRMs?were seprated in the molecular network and only one drug-resistant cluster was found,carrying the drug resistance mutation?DRM?L210W.Compared with 2004-2005,the major subtypes in China have changed from B'?71.4%?to CRF01_AE?39.0%?and CRF07_BC?35.6%?.No significant difference was found in the prevalence of TDR or specific mutations.There was no significant difference in the rates of TDR among different routes of transmission or subtypes between the two study periods.However,the rate of TDR in the 16-25 year-old group was significantly higher in 2004-2005?P=0.01?.In the molecular network analysis,it was found that the CRF65 CPX strain,a newly reported CRF in 2014,formed an independent cluster.A total of 52 CRF65 CPX sequences were collected from 8 provinces in China,and the overall rate of TDR was 5.8%.Bayesian analysis showed that the time of origin was 1999.The strain was transmittied to homosexual individuals in 2003 and lost two protective gene HLA-B*2702 and HLA-B*5103 restricted CTL epitopes.The second sectionThis study investigated 4205 HIV-infected patients in Beijing from 2005 to 2015.The mainly subtypes were CRF01_AE?49.5%?and CRF07_BC?25.0%?.The proportion of CFR01_AE,CFR07_BC,CFR55₀1B,CFR68₀1B and the unknown subtypes gradually increased,and the proportion of subtype B gradually decreased.The overall rate of TDR was 4.4%.The prevalence of TDR to NRTIs,NRTIs,and PIs were 1.4%,1.1%,and 2.3%,respectively.The rate of NRTIs had a decreasing trend?P=0.02?.At a genetic distance threshold of 0.5%,a total of 163 clusters were identified,and the overall rate of clustering was 25.3%?1704/4205?,with an average of 10 nodes per cluster.The vast majority of men who have sex with men?MSM?,heterosexual men,injection drug useing man,and heterosexual women are mainly connected to MSM?89.7%,84.7%,84.6%,50.0%?.During 2005-2011,2012-2013,and 2014-2015,the majority individuals can not enter the network?74.0%,71.3%,and 77.8%?.Those who did not enter the network were mainly those living in Beijing and registered in other citys?36.8%,68.1%and 68.8%;42.6%,75.7%and 63.8%?.In this study,a molecular network was constructed using the bootstrap value plus genetic distance method?Cluster Picker?for supplementary analysis.With a bootstap value ?90%and a gene distance<4.5%,a total of 269 propagation clusters were identified.The overall rate of clustering was 39.7%?1674/4205?.There was an average of 4 nodes per cluster.During 2005-2011,2012-2013,and 2014-2015,the majority individuals can not enter the network?66.1%?59.2%and 57.6%?.Those who did not enter the network were mainly those living in Beijing and registered in other citys?39.2%?67.6%and 67.3%;43.3%?75.2%and 62.9%?.The results are consistent with the genetic distance method.ConclusionIn the past 10 years,the prevelance of TDR remain stable at low levels levels?<5%?in China.CRF01_AE spreads for multiple small clusters,while CRF07_BC mainly spreads through a large cluster.The widespread of complex CRFs such as CRF65_CPX needs highly attention.The proportion of CRF01_AE,CRF07_BC,CRF55₀1B,CRF68₀1B and unknown subtypes among HIV-infected individuals in Beijing continued to increase from 2005 to 2015,and the subtype complexity of epidemic strains increased.There is a close relationship between MSM and individuals in other risk exposure.Strengthening interventions for MSM can reduce the risk of individuals in other risk exposure.There are a large number of foreign infectors who cannot enter the local molecular network in Beijing.It is suggested that the monitoring of foreign infectors should be strengthened through cross-regional molecular networks.