HIV-1 Molecular Epidemiology And Drug Resistance Mutations In Hebei Province

Hebei is a northern province of China,with 11 prefectures,and the gateway to Beijing,and surrounds Beijing and Tianjin,neighboring Henan Province to the south.In 1989,the first HIV epidemic in Hebei was confirmed among Chinese overseas workers returning from Africa in Shijiazhuang prefecture.In the 1990 s,local human immunodeficiency virus?HIV?outbreaks occurred in Xingtai and Langfang,and many individuals infected with HIV-1 through blood transmission were identified.The newly diagnosedHIV/acquired immune deficiency syndrome?AIDS?positive cases had been more and more every year.By the end of 2015,a total of 7,303 HIV/AIDS cases had been reported.For 27 years,the predominant drivers of HIV-1 prevalence in Hebei had obviously shifted,and men who have sex with men?MSM?transmission had become the most common route.In this study,HIV-1 overall epidemic in Hebei were analyzed.Moreover,we have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013,and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei.HIV-1 drug resistance mutations have been evaluated among newly diagnosed HIV-1 positive individuals in 2013.The surveillance of HIV-1 transmitted drug resistance?TDR?have been performed among youths aged 16-25,and recently infected MSM in this area.Our findings are as below:1.In Hebei,the newly diagnosed HIV-1 positive cases have been more and more every year.The predominant drivers of HIV-1 epidemic in this area have obviously shifted,and MSM transmission has become the most common route.2.Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed na?ve individuals.The four main genotypes were circulating recombinant form?CRF?01_AE?53.4%?,CRF07_BC?23.4%?,subtype B?15.9%?,and unique recombinant forms?URFs,4.9%?.Within one year,three new genotypes?subtype A1,CRF55₀1B,CRF65_cpx?,unknown before in Hebei,were first found among men who have sex with men?MSM?.All nine genotypes were identified in the sexually contracted HIV-1 population.Among 30 URFs,six recombinant patterns were revealed,including CRF01_AE/BC?40.0%?,CRF01_AE/B?23.3%?,B/C?16.7%?,CRF01_AE/C?13.3%?,CRF01_AE/B/A2?3.3%?and CRF01_AE/BC/A2?3.3%?,and two potential CRFs were identified.The phylogenetic analysis indicated that the main HIV-1 strains were introduced into Hebei through different transmission routes from neighbouring,southernwest and southern provinces of China.Particularly,four big MSM transmission clusters were identified among the sexual contact population between Hebei and its neighbouring provinces such as Beijing,Liaoning and so on,including two CRF01_AE clusters,one subtype B cluster and one CRF07_BC cluster,which suggested that there was the close relationship of HIV-1 spread between them.All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact,especially through MSM.3.For this study,50 HIV-1 plasma samples of the recently infected MSM were amplified and sequenced.Multiple subtypes were identified by phylogenetic analyses of HIV-1 gag,env and pol gene regions,including CRF01_AE?56.0%?,CRF07_BC?30.0%?,subtype B?12.0%?,unique recombinant forms?URFs,6.0%?.CRF01_AE was the most epidemic genotype.Three recombination patterns of URFs were identified as follows: CRF01_AE/BC,CRF01_AE/B and CRF01_AE/C.4.Among newly diagnosed naiveHIV-1 positive individuals in 2013,the prevalence of HIV-1 drug resistance mutations was 16.2%?109/672?by the analyses of HIV-1 pol gene,including Protease inhibitors?PIs?mutations?6.3%,42/672?,Nucleoside reverse transcriptase inhibitors?NRTIs?mutatios?2.4%,16/672?and Non-nucleoside reverse transcriptase inhibitors?NNRTIs?mutations?8.6%,58/672?.Of them,the prevalence of dual mutations in two gene coding regions,multiple mutations in three gene coding regions and multiple mutations in single gene coding region was 0.7%?5/672?,0.15%?1/672?and 0.4%?3/672?,respectively.This complicated mutation pattern reduced the therapeutic effect of all drugs in the Stanford HIV Drug Resistance Database with the exception of five NRTIs?3TC,ABC,DDI,FTC and TDF?.The prevalence ofTDRamong youths aged 16-25 and recently infected MSM at MSM surveillance points was 6.6% and 2.1%,respectively.The phylogenetic analysis indicated that HIV-1 resistant strains located in different clusters associated with main genotypes,especially big MSM clusters,were related to neighboring provinces.