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HIV-1 Genetic Diversity And Transmitted Drug Resistance In Beijing

Posted on:2018-07-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:M Q HaoFull Text:PDF
GTID:1484306338977209Subject:Pathogen Biology
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Beijing has made great efforts to respond to HIV epidemic.The government is active in exploring different ways in fighting against HIV such as popularizing oral fluid HIV testing and anonymous urine HIV detection,expanded testing and early treatment.Early antiviral therapy can significantly reduce the mortality of HIV-infected persons and improve the ability of immune system to rebuild.At the same time,very early treatment can significantly reduce the viral load in patients with acute HIV infection and reduce the risk of HIV transmission at the acue infection stage.Beijing has made a great effort in establishing the "green channel" to ensure the patients newly diagnosed can benefit from ART more conveniently and timely.It was reported that the minimal time interval between diagnosis and receiving of free ART is reduced from 100 days in 2011 to 7 days in 2016.By the end of June 2016,a total of 12,637 patients had received free ART in Beijing,of which 11,379 are still alive.HIV antiviral treatment coverage has reached 85.7%and the virological success rate of treatment has reached 98.5%in Beijing.The high mutability of HIV-1 virus has brought great problems to the development of HIV vaccine and HIV antiviral treatment.The emergence of drug-resistant strains will lead to the failure of HIV antiretroviral therapy.With the increasing of HIV antiretroviral coverage in Beijing,the risk of transmission for HIV drug resistant strains can not be ignored.Therefore,it is of great significance to carry out the detection of HIV-1 transmitted drug resistances(TDR)through which we can evaluate the effectiveness of antiviral therapy and the prevalence of drug-resistant strains.The objective of our study was to determine the prevalence of TDR and the diversity of HIV among treatment-naive HIV infected people in 2014-2016.We obtained 9 near full-length genome sequences which can be difined as new forms of recombinant strains.At the same time,in order to analysis the increasing prevalence of HIV in young students and people over 50 years old in Beijing,the HIV molecular epidemiological survey was carried out among them for the first time.In this study,we rebuilt the epidemic history of HIV-1 CRF65_cpx in Beijing and speculated the time when it was introduced into Beijing.An overall prevalence of TDR of 3.9%was detected in treatment-naive HIV infected people in 2014-2016.Depending on WHO threshold survey guidelines,the rate indicated a low-level prevalence of TDR in Beijing.TDR to protease inhibitors(PI)were detected in 2.0%of all people in the study.TDR mutations to nucleoside reverse transcriptase inhibitors(NRTI)were detected in 1.0%of them and non-nucleoside reverse transcriptase inhibitors(NNRTI)were 1.3%.The rate of TDR among Subtype B was the highest(6.2%)followed by 5.0%in CRF01_AE and 1.5%in CRF07_BC.For the student population and people over the age of 50,the prevelence of drug resistance were 2.1%and 3.6%,lower than it in the whole population.However,the subtype distribution was significantly different bewteen people above 50 years old and the whole population.The most prevalent subtype of HIV among people over 50 years old was CRF07_BC,compared with CRF01_AE in the whole population.In the genetic diversity of HIV,15 subtypes and 219 cases of URFs were detected in 2,762 untreated HIV infected people in 2014-2016.The proportion of URFs was as high as 7.9%.A total of 29 kinds of recombinant forms were predicted from 219 URFs samples.A total of 9 sequence information of near full length genome of the HIV was obtained.The recombination pattern and breakpoint sites were different for each of them in which they could be identified as 9 different new forms of UFRs.The detection of various URFs reflects the high genetic diversity of HIV prevalence in Beijing.By analyzing the subtype distribution among the whole HIV infected people,we found that the CRF65_cpx subtype which was first reported in 2014 in Yunnan province had been detected in 1%of HIV infected people in Beijing.In order to curb the prevalence of this kind of new subtypes,we analyzed the epidemiological characteristics of it and reconstructed its epidemic history.The study found that the subtype was introduced in Beijing from 2004.7(95%of the confidence interval:2002.1-2007.4).After a brief decline period of epidemic in 2009-2010,it enterd a period of rapid growth in the MSM population in which the main epidemic cluster of CRF65_cpx subtype in the N-J tree was evolved in Beijing.
Keywords/Search Tags:HIV-1, treatment naive population, transmitted drug resistances, recombinant virus
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