Study On HIV Genetic Variation And Its Application In AIDS Prevention And Treatment

Human immunodeficiency virus(HIV)is the most variable virus and produced various subtypes and their circulating recombinant forms(CRF)with certain population and regional distribution during global epidemic.Genetic variation and evolution is an important research field of HIV and has wide range application in AIDS prevention and treatment.Our study on HIV genetic variation is designed to trace the HIV epidemic,to improve the accuracy of self-reporting data by building molecular transmission network and to analyze HIV tropisms based on coreceptor shift from CCR5(R5)to CXCR4(X4).Previous studies have reported that different HIV subtypes and their genetic clusters domestrated different CD4 cell loss and disease progression.During aniviral treatment,even though the virus was effectively suppressed after antiviral treatment,immune reconstitution was blocked in about 20% of AIDS patients.Therefore,it is necessary to examine the mechanisms and factors associated with poor immune recorvery in both host and virus including subtypes and clusters and viral tropisms.Based on the antiviral treatment cohort and national molecular epidemiological survey,we initiated the study by analyzing HIV gene variation and phenotype prediction.Then,we build the HIV transmission clusters and use it as a parameter on the determining model to evaluate the accuracy of self-reported infection route data.Finally,a variety of methods were used to analyze the mechanisms and influencing factors for the poor immune reconstitution in patients with antiviral therapy.The following results have been obtained.In molecular epidemiology study,we recrumented 674 HIV infected individuals.CRF01?AE(63.6%)and CRF07?BC(18.4%)were two the main HIV-1 strains.Of the CRF01?AE,cluster 4(65.5%)was predominant,followed by cluster 1(14.7%)and cluster 5(8.2%).We also detected two novel unique recombinant forms of HIV-1 strain derived from CRF01?AE and CRF07?BC.The pol sequences of 1805 subjects from National HIV Molecular Epidemiology Survey were used to build the molecular network.Adding the molecular network parameter and using decision tree model,we evaluated the self-reporting data of infection routes for all subjects.The model analysis found that the accuracy of the self-reported data by women reporting heterosexual infection and MSM reporting homosexual infection are 100% and 96.8% respectively.On the contrary,the accuracy of men selfreporting heterosexual transmission is only 71.4%,with 28.6% error of actual homosexual transmission.It is revealed that combining transmission network and determine modeling,we can significantly correct the error in self-reporting due to social stigma on MSMs.The improved accuracy in epidemic data will greatly faciliate the pr�cising AIDS prevention and control.We recruited 674 antiviral treatment(HAART)patients in a cohort to study their immune reconstitution during therapy.We used a generalized estimation equation to evaluate the factors affecting HAART effects.We found that baseline CD4 T cell counts,subtypes/clusters,tropism,and age were independent factors affecting immune recovery during HAART.Poorer immune reconstitution of low pencentage,low level and longer time needed,were found in patients infected by CRF01?AE compared with BC,and in CRF01?AE cluster 1 compared with cluster 4 and cluster 5.We found that high proportation of X4 coreceptor usage contributed to cell demage and decline CD4 count before HAART.Further study revealed that the mutation of specific amino acid of the V3 region resulted in change of net charge and PNGS,which was the basis of transformation from R5 to X4.Conclusions:CRF01?AE and CRF07?BC subtypes are the prevalent HIV-1 strains in HAART patients in Zhejiang Province.We constructed the molecular network to track the transmission chains and corrected the bias in self-reporting data of male heterosexual transmission,which is suppressed by social stigma for homosexual activity.We found that CRF01?AE,its cluster 1 and low baseline CD4 counts are associated with poor immune recovery in HAART cohort.This is due to enhanced X4 co-receptor tropisms in CRF01?AE and its cluster 1 infected people,who should be at the top priority for receiving HAART.Considering the high prevalent of CRF01?AE and its novel recombinants appearance in Zhejiang,special attention on monitoring these strains should be given by local health authority.