Analysis Of The Subtypes Of The Prevalent Virus Strains And The Transmission Characteristics Of Drug-resistant Strains Among HIV-infected Persons Aged 16-25 In My Country

BackgroundDue to the highly variable characters of HIV gene and the selection of different antiviral drugs,the HIV patient would be resistant to these drugs.Whereafter,the drug-resistance HIV strains can be transmitted to the public.If the transmission of drug-resistance exists extensively around the world in the future,the therapeutic effect of existing drugs will be greatly weakened and even failure.According to the World Health Organization?WHO?Drug Survelliance Program,the treatment-naive HIV-infected teenagers and young adults between 16 and 25 years old who were exposed to high risk behavior for a short time can be approximatively considered as newly diagnosed patients,so the prevalence rate of this group can be treated as rate of transmitted drug-resistance.we investigated the genetic characterisitcs of HIV strains and the spread of drug resistant strains in the newly reported patients from 8 years cross-sectional study.Objective1.The aim of the study was to analyze the distribution of subtype and variation of HIV virus among newly infected patients between 16 to 25 years old from 2008 to 2015.2.The aim of the study was to realize the trends of HIV subtypes and transmitted drug resistance in the context of ART.Explore the factors influencing transmission of the drug-resistance and to provide scientific data for the improvement of antiviral treatment regimen.3.Use the molecular network to estimate the effect factors of HIV high risk group,positioning highly active HIV-transmitted populations,then wen can explore the implementation of the various prevention measures of high risk population.Results:1.Epidemiological characteristics of juvenile HIV-infected patients in recent eight yearsA total of 4275 patients with HIV were enrolled into this study between 2008?2015 in china.74.9%were male,65.9%were Han nationality and 57.4%were not married.The main transmission route were sexual intercourse?82.7%?,in particular the route of male same-sex?45.7%?,the other main route was injected drug use?10.0%?.The high prevalence area were Southwestern region?30.1%?and Eastern region?15.4%?.The sequences were mainly obtained from CRF01_AE?39.2%?and CRF07_BC?38.9%?.then B?7.3%?and CRF08_BC?4.2%?.These sequences also included some other recombination strains,such as CRF55₀1B?1.7%?and CRF59₀1B?0.2%?.In eight years of continuous longitudinal observation of HIV study,we found that CRF01_AE increased and CRF07_BC decreased over time?P<0.01?.The clusters of the two major subtype also had showed abvious trend.In CRF01_AE,cluster 4 and cluster 5 which were active in msm group increase over time,nevertheless cluster1 and cluster2 which were active in heterosexual group and injecting drug users had a decreased trend?Feng,Y.The rapidly expanding CRFOI_AE epidemic in China is driven by multiple lineages of HIV-1 viruses introduced in the 1990s?.In CRF07_BC,cluster-MSM which was active in homosexual group increased dramatically and cluster-IDU which was active in hetersexual group was anaginst that?Li,Z.Trends of HIV subtypes and phylogenetic dynamics among young men who have sex with men in China,2009-2014?.Then subtype B was significantly decreased in recent years,while CRF55₀1B was also a new recombination subtype discovered in chinese msm population in recent years,and this subtype had formed a trend of clustering epidemic.2.Surveillance of transmitted drug resistance in 8 consecutive years in ChinaThe overall prevalence of TDR HIV among the study population of 4275 cases was 3.1%?131/4275,range:1.7%-3.9%?.1.0%had resistance to nucleoside/nucleotide reverse transcriptase inhibitor?NRTIs?;1.1%had resistance to nonnucleoside reverse-transcriptase inhibitor?NNRTIs?;and 1.2%had resistance to protease inhibitors?PIs?.There were 9 and 2 patients who respectively had double?NRTIs+NNRTIs?and multiple?NRTIs+NNRTIs+PIs?drug resistance.The prevalence of transmitted drug resistance was almost 3%among the 8 years,and we didn't find a statistically significant increase over time in the proportion of participants with TDR,nor was it significant when only TDR to NRTIs,NNRTIs or to PIs were considered.The result of single logistic analysis with drug resistance as dependent variable demonstrated that patients whose subtype was CRF01_AE?ORvalue=1.9,95%CI:1.2-2.8?,the other factors had no significant difference.There are 43 strains which had the NRTIs drug-resistant mutations,the thymidine-associated mutations predominated in our study.Of these type of mutations,T215?M184 and L210 mutation were the high frequent variations.among these,M184 and L210 had increased trends,and T215 had decreasing trends.Among 45 NNRTIs mutations,K103 increased over time,and Y188/Y181 mutations showed an decreasing trend.Then in the 53 patient with PIs mutations,M46 was the most frequent PIs mutation,and it showed an decreasing trend.We also found a transmitted drug-resistant cluster in subtype B,whose mutation was multi-drug resistant mutations,including L90M,T215S and Y188L,and the two patients of this drug-resistant cluster came from different region in Hangzhou.3.We used the molecular network to study the activity of different population through network rate and degree valueWe established molecular network to compare the clustered rate between different groups.In order to accurately determine the vitality of each HIV strains,we imported the degree value.Meanwhile,we divided the degree of all clustered strains into 4 levels according to he quartile method,which can represent different risk group.Amone the most risk level of patients,we could find that the population which were homosexual route and CRF07 BC were the high risk group.Meanwhile,we used the logistic analysis to analyze the influencing factors of the leve14,we discovered that the high risk group population has many characters,including male,same-sex sexual transmitted route,and the subtype of CRF07 BC.In the level 4,we also found 10 drug-resistant strains.Among them,9 were the subtype of CRF07 BC,8 were not married,and the main transmitted way was homosexual route,mainly in 2010-2015.These 10 drug-resistant strains were mainly distributed in North,south,central and southwest china.there are 4 strains whose degree were more than 100,which reminder the emergency of take control of transmitted drug resistance group.Conclusion:1.The treatment-naive HIV-infected teenagers and young adults between 16 and 25 years old who were exposed to high risk behavior for a short time can be approximatively considered as newly diagnosed patients.The major subtype of our study were CRF01_AE and CRF07_BC,The transmitted rate of CRF07 BC also higher than other subtypes.Cluster 4 and cluster 5 in CRF01_AE and cluster-MSM in CRF07 BC which were active in msm group increased.Then subtype B was significantly decreased in recent years,while CRF55₀1B was also a new recombination subtype discovered in chinese msm population in recent years,and this subtype had formed a trend of clustering epidemic2.The overall prevalence of TDR HIV among the study population was at a low-level prevalence,and the prevalence was relatively stable over time.M184 and L210 which were the main mutations in NRTI and K103 which was in NNRTIs mutations had a increased trend over time.In general case,the drug-resistant strain were sporadic in HIV patients,but we also found a transmitted cluster which had multiple-drug resistance?L90M,T215Y and Y188L?in subtype B.3.According to construct the molecular network,we proved that the high risk group were male,homosexual and CRF07 BC.Meanwhile,we also found there were 10 drug-resistant strain in leve14 of degree.The existence of these strains show a great risk of transmitted drug-resistance,it woule increase the probability of antiviral treatment failure.